NEJM Evid. 2026 Nov;5(11):EVIDpha2600217. doi: 10.1056/EVIDpha2600217. Epub 2026 Oct 27.

ABSTRACT

AbstractUsing data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Program, we examined colorectal cancer incidence rates in the United States between 2000 and 2023. SEER 21 covers 45.8% of the U.S. population. The age-adjusted incidence rate was 55.2 per 100,000 (95% CI, 54.8 to 55.6) in 2000, 36.7 per 100,000 (95% CI, 36.4 to 37.0) in 2022, and 38.3 per 100,000 (95% CI, 38.0 to 38.6) in 2023. The apparent increase in 2023 was the first since the inception of SEER 21 and warrants additional surveillance and investigation.

PMID:42937424 | DOI:10.1056/EVIDpha2600217

The post Colorectal Cancer among U.S. Adults, 2000-2023 appeared first on Fight Colorectal Cancer.

Gastroenterol Clin North Am. 2026 Dec;55(4):543-564. doi: 10.1016/j.gtc.2026.05.013. Epub 2026 Sep 16.

ABSTRACT

Adenomatous polyposis, defined clinically as the occurrence of 10 or more cumulative adenomatous colorectal polyps, is the most common form of polyposis. The phenotype may be classic with hundreds to thousands of polyps or attenuated with less than 100 polyps. Genetic counseling and multi-gene panel testing that includes at least all known adenomatous polyposis syndromes should be completed for either presentation. This article summarizes the established and emerging genetic etiologies of adenomatous polyposis, highlights current challenges in diagnosis and management, and discusses advances in genetic testing and potential targeted therapies.

PMID:42933933 | DOI:10.1016/j.gtc.2026.05.013

The post Adenomatous Polyposis Syndromes appeared first on Fight Colorectal Cancer.

Fam Cancer. 2026 Oct 27;25(4):100. doi: 10.1007/s10689-026-00614-8.

ABSTRACT

Lynch syndrome is the most common hereditary cancer predisposition syndrome, yet remains substantially underdiagnosed despite effective risk reduction strategies. Identification of affected individuals is critical to enable cancer prevention, early detection, and cascade testing of at-risk relatives. Multiple complementary approaches to Lynch syndrome detection exist, each with distinct strengths and limitations across clinical settings.In this review, we summarize established and emerging strategies for Lynch syndrome identification in those with a personal and family history of colorectal neoplasia. Tumor-based mismatch repair deficiency testing remains an effective and cost-efficient screening strategy but is limited by incomplete implementation and imperfect sensitivity. Direct germline testing can overcome some of these limitations and identify additional hereditary cancer syndromes, though considerations regarding yield, cost, and interpretation remain. Family history-based approaches and risk prediction models offer additional tools but are constrained by challenges in data collection and clinical uptake.Optimizing Lynch syndrome identification will require integration of these strategies alongside system-level interventions to improve access, uptake, and equity in genetic evaluation.

PMID:42944990 | DOI:10.1007/s10689-026-00614-8

The post Diagnostic yield and clinical utilitY of strategies for identifying Lynch syndrome in those with colorectal neoplasia appeared first on Fight Colorectal Cancer.

JAMA Netw Open. 2026 Oct 1;9(10):e2639013. doi: 10.1001/jamanetworkopen.2026.39013.

ABSTRACT

IMPORTANCE: Colorectal cancer (CRC) screening is suboptimal among people in traditionally underserved populations, many of whom receive primary care at federally qualified health centers (FQHCs). Mailed fecal immunochemical test (FIT) outreach improves screening, especially in underserved populations, but questions remain about impact over time.

OBJECTIVE: To evaluate the effectiveness of centralized annual mailed FIT outreach delivered over 3 years to increase CRC screening in FQHCs.

DESIGN, SETTING, AND PARTICIPANTS: This cluster randomized clinical trial was conducted between June 1, 2021, and May 31, 2024. Sixteen clinics from 2 FQHCs in Southern California were randomly assigned to mailed FIT outreach or usual care for patients aged 50 to 75 years and not up to date with screening.

INTERVENTION: Intervention components followed best practices for mailed FIT outreach and included educational primers, FIT kits, and telephone reminders.

MAIN OUTCOMES AND MEASURES: The primary outcome was the proportion of individuals up to date with any CRC screening after 3 years of intervention (point prevalence); screening at 2 years was a secondary outcome. Due to a resource constraint-related protocol modification, mailed FIT outreach began earlier in year 3, such that some individuals who completed screening in year 2 were not yet due for repeat FIT.

RESULTS: Among 16 clinics serving 20 250 patients, 6 clinics serving 8334 individuals at baseline (4435 aged 55-64 years [53.2%]; 4896 female [58.7%]; 341 Asian [4.1%], 238 Black [2.9%], 2390 Hispanic [28.7%], and 4371 non-Hispanic White [52.4%]) were randomized to intervention and 10 clinics serving 11 916 individuals at baseline (6443 aged 55-64 years [54.1%]; 7250 female [60.8%]; 699 Asian [5.9%], 355 Black [3.0%], 4635 Hispanic [38.9%], and 4436 non-Hispanic White [37.2%]) were randomized to usual care. At year 3, screening was 39.4% (95% CI, 36.3% to 42.6%) in intervention clinics vs 36.5% (95% CI, 31.2% to 42.2%) in usual care clinics, which was not a statistically significant difference (2.9 percentage points; 95% CI, -3.2 to 9.0 percentage points). At year 2, screening was 37.8% (95% CI, 35.2% to 40.4%) in intervention clinics vs 27.0% (95% CI, 21.8% to 32.9%) in usual care clinics (difference, 10.8 percentage points; 95% CI, 4.9 to 16.7 percentage points).

CONCLUSIONS AND RELEVANCE: This study’s findings suggest that centralized mailed FIT outreach could increase CRC screening in FQHCs serving populations with persistent disparities, although maintaining intervention fidelity and providing ongoing implementation support over time are needed for consistent impact.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04941300.

PMID:42905707 | DOI:10.1001/jamanetworkopen.2026.39013

The post Fecal Immunochemical Test Outreach for Colorectal Cancer Screening in Community Health Centers: A Randomized Clinical Trial appeared first on Fight Colorectal Cancer.

On October 19, 2026, the FDA approved dostarlimab (Jemperli), an immunotherapy, for adults with stage II or III rectal cancer that is dMMR or MSI-H. The benefit is big: for eligible patients, this treatment can replace chemotherapy, radiation, and surgery entirely. Instead of going through all three, you may be able to treat your cancer with immunotherapy alone, and avoid their lasting effects on bowel, bladder, sexual function, and fertility. In the AZUR-1 trial, 71% of patients were treated with dostarlimab alone and needed no further treatment, no chemo, no radiation, and no surgery. It is not for everyone, because only tumors that test dMMR/MSI-H respond this way. Below is who qualifies, what to expect, the possible side effects, and the questions to bring to your care team.

Who qualifies for dostarlimab? 

You may be a candidate for dostarlimab if all of the following are true: 

• You are an adult with rectal cancer. 
• Your cancer is stage II or III (locally advanced, meaning it has grown into nearby tissue or lymph nodes but has not spread to distant organs). 
• Your tumor is dMMR or MSI-H, confirmed by an FDA-authorized biomarker test. 
• You have not yet started treatment for this cancer. 

About 5–10% of rectal cancers are dMMR/MSI-H. The only way to know if yours is one of them is a biomarker test on your tumor tissue, and it can’t be seen on a scan or guessed from your symptoms or stage. 

Who doesn’t qualify? 

This treatment isn’t the right fit for everyone. It is not approved for people whose situation includes: 

• A tumor that is proficient mismatch repair (pMMR) or microsatellite stable (MSS), which is the large majority of rectal cancers, and these tumors don’t respond to immunotherapy the same way. 
• Rectal cancer that is stage I, or stage IV (metastatic, spread to distant organs), since the approval covers stage II/III. 
• Cancer for which you’ve already begun chemotherapy, radiation, or surgery. 
• An unknown biomarker status, so you’d need testing first to find out whether you qualify. 

If you don’t qualify for dostarlimab, it does not mean you’re out of options. Standard treatments, including surgery, radiation, and chemotherapy, remain effective, and your care team can walk you through what’s best for your situation.

What are the benefits, and how is it given? 

• How it’s given: By IV every three weeks, for nine treatments over about six months. No chemotherapy or radiation. 
• The results: In the trial, 71% of patients were treated with dostarlimab alone and needed no other treatment. The formal 12-month complete-response rate was 47% by independent review (68% by the treating doctors’ own assessment). So far, among patients who had a complete or near-complete response, none have seen their cancer come back, after about two years of follow-up (median 26 months). 
• If it works: You’ll have regular check-ups (exams, scans, and scopes) instead of surgery. 
• If it doesn’t fully work: Surgery, radiation, and chemotherapy are still options. 

What are the side effects? 

Dostarlimab is generally better tolerated than chemotherapy, but it can still cause side effects. In the AZUR-1 trial, the most common were: 

• Fatigue (about 32% of patients) 
• Rash (about 22%) 
• Diarrhea (about 18%) 
• Itchy skin (about 17%) 

About 1 in 5 patients (20%) had a serious side effect, and 3% stopped treatment because of one. 

Because dostarlimab works by activating your immune system, it can sometimes cause the immune system to attack healthy organs, which are called immune-related side effects. These can affect the skin, bowel, lungs, liver, hormone glands, and other areas, and can appear suddenly, during or even after treatment. They are most manageable when caught early, so tell your care team right away about new diarrhea, rash, trouble breathing, or unusual tiredness. Your team will check your blood and other tests during treatment to watch for these. 

How Do I Know If My Tumor Is dMMR/MSI-H? 

The only way to know is a biomarker test on your tumor tissue. 

• To qualify for this treatment, your dMMR/MSI-H status needs to be confirmed with an FDA-authorized test. 
• It can’t be seen on a scan or guessed from your symptoms or stage. 
• Because this treatment replaces chemotherapy, radiation, and surgery, testing needs to happen before treatment begins. 
• The same test can also reveal inherited risk, like Lynch syndrome, that may matter for your family. 

Not sure if you’ve had biomarker testing? We encourage all patients to ask their care team: “Has my tumor had biomarker testing, and what were the results?” 

Need help understanding your biomarker report? ChatCRC’s free biomarker report reader can explain your results and help you prepare questions. Start at chatbot.fightcolorectalcancer.org or text 318-242-8272 (318-CHATCRC). Explore more in our Resource Library. 

Why Is This Approval Important? 

This is the first and only immunotherapy approved for locally advanced rectal cancer. For many patients, it may mean avoiding chemotherapy, radiation, and surgery altogether. 

For decades, treatment for stage II and III rectal cancer has relied on those three treatments. They work, but they can leave lasting effects: 

• Changes in bowel, bladder, and sexual function 
• Infertility 
• A higher risk of a second cancer later in life 

For people with dMMR/MSI-H tumors, dostarlimab offers a different path, one built around the biology of their cancer. National cancer treatment guidelines (NCCN) already recommended six months of immunotherapy as the preferred approach for dMMR/MSI-H locally advanced rectal cancer; what’s new is that there is now an FDA-approved treatment with a label for this use. The FDA moved quickly on this approval, granting it Breakthrough Therapy and Priority Review status because of how strong the early results were.

What Is the AZUR-1 Trial? 

AZUR-1 is the clinical trial the FDA based this approval on, and the results shared in this article come from it. It tested whether dostarlimab alone could clear dMMR/MSI-H rectal cancer so patients could skip chemotherapy, radiation, and surgery. 

• Who was in it: 154 adults with stage II or III dMMR/MSI-H rectal cancer who had not yet started treatment. 
• What they received: Dostarlimab alone, by IV every three weeks for six months (nine treatments). 
• What happened next: Patients whose cancer disappeared were watched closely with regular exams and scans instead of having surgery. 

Learn more on ClinicalTrials.gov. 

What is dMMR/MSI-H rectal cancer? 

About 5–10% of rectal cancers are mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H). These tumors can’t properly fix mistakes in their DNA, so they build up many genetic changes. Those changes make the tumor easier for the immune system to recognize, which is why immunotherapies like dostarlimab often work so well for this group. dMMR/MSI-H tumors are most common in colorectal, endometrial, and other digestive-tract cancers, but can show up in other solid tumors too.

What do we know, and what are we still learning? 

What we know: In the AZUR-1 trial, 71% of patients were treated with dostarlimab alone and needed no further treatment. Among those who had a complete or near-complete response, none have had their cancer return so far (median follow-up about 26 months). 

What we’re still learning: This is an accelerated approval, which the FDA grants when early results are strong for a serious condition. We don’t yet know the long-term chance of the cancer returning, because patients haven’t been followed long enough. Results checked by an independent review panel are also still coming in, and continued approval may depend on further study. Full trial results will be presented at the European Society for Medical Oncology (ESMO) Congress in October 2026. 

What does this mean for you? The early results are very encouraging, and choosing this path means committing to close, regular check-ups. It’s worth talking with your care team about how to weigh a strong early result while the long-term data continue to mature. 

Related reading: Earlier in October 2026, the FDA also approved an immunotherapy combination for stage III dMMR colon cancer. Read our summary: FDA Approval: Immunotherapy for Stage III dMMR Colon Cancer. 

Considering This Treatment? Questions for Your Care Team 

Choosing a treatment is a decision you and your care team make together. Dostarlimab offers many people with dMMR/MSI-H rectal cancer a real chance to skip chemotherapy, radiation, and surgery. But it’s new, the long-term results are still coming in, and like any cancer treatment it can cause side effects. The best choice for you depends on your biomarker results, your health, and what matters most to you. 

These questions can help guide your conversation with your oncologist. 

What this treatment could do for me 

• How likely is it that dostarlimab alone could clear my cancer? 
• How will we know if I’ve had a complete response? 
• If the cancer doesn’t fully go away, or comes back, what are my next options? 
• We don’t yet know the long-term chance of the cancer returning. How should that factor into my decision? 

Side effects and monitoring 

• Which side effects are most common, and which are most serious? 
• Since this treatment works through my immune system, which symptoms should I report right away? (Immune-related side effects, such as new diarrhea, rash, trouble breathing, or unusual tiredness, can appear suddenly and are easiest to manage when caught early.) 
• What tests will you use to check on me during treatment? 
• If I have a reaction, would we pause treatment, treat the side effect, or stop? 

My life and priorities 

• If I don’t have surgery, what will my follow-up visits and scans look like, and for how long? 
• Compared with standard treatment, how might this affect my bowel function, sexual health, or fertility? 
• How might treatment fit with my work, daily life, and the people who support me? 

Getting the full picture 

• Does this cancer center have experience treating rectal cancer this way? 
• Would a second opinion help before I decide? 
• Are there clinical trials I should know about? 

There’s no one right answer for everyone. Use these questions to help you and your care team find the path that fits you. 

Frequently Asked Questions 

What is dostarlimab (Jemperli)? 

Dostarlimab is an immunotherapy that helps your immune system find and attack cancer cells. On October 19, 2026, the FDA approved it for adults with stage II or III dMMR/MSI-H rectal cancer. 

Is dostarlimab chemotherapy? 

No. It’s an immunotherapy, and for this approval it’s given on its own, without chemotherapy or radiation. 

How is dostarlimab given for rectal cancer? 

In the AZUR-1 trial, patients got dostarlimab by IV every three weeks, for nine treatments over about six months. Your care team will confirm the schedule and dose that’s right for you. 

Will I still need surgery? 

Maybe not. In the trial, 71% of patients were treated with dostarlimab alone and needed no surgery or other treatment. If the cancer doesn’t fully respond, surgery and other standard treatments are still options. 

Who is not eligible for dostarlimab? 

Dostarlimab is not approved for rectal tumors that are pMMR/MSS (the large majority), for stage I or stage IV (metastatic) rectal cancer, or for people who have already started chemotherapy, radiation, or surgery. If your biomarker status is unknown, you’d need testing first to find out whether you qualify. 

What are the most common side effects? 

The most common side effects in the AZUR-1 trial were fatigue, rash, diarrhea, and itchy skin. About 1 in 5 patients had a serious side effect. Because dostarlimab works through the immune system, it can also cause immune-related reactions in various organs, which are most manageable when reported early. 

Disclaimer 

This article is for educational purposes only and is not medical advice. Treatment decisions should always be made with your own oncology care team. 

Sources 

1. U.S. Food and Drug Administration. “FDA grants accelerated approval to dostarlimab for locally advanced rectal cancer.” October 19, 2026. 
2. GSK. “Jemperli (dostarlimab-gxly) approved in US as first and only immunotherapy for adults with MSI-H/dMMR locally advanced rectal cancer.” October 19, 2026. 
3. JEMPERLI (dostarlimab-gxly) Prescribing Information. GSK. 
4. AZUR-1 trial. “A Study of Dostarlimab in Untreated dMMR/MSI-H Locally Advanced Rectal Cancer.” ClinicalTrials.gov, NCT05723562. 
5. Cercek A, et al. “PD-1 Blockade in Mismatch Repair–Deficient, Locally Advanced Rectal Cancer.” New England Journal of Medicine. 2022;386:2363-76. doi.org/10.1056/NEJMoa2201445 
6. Fight Colorectal Cancer. “FDA Approval: Immunotherapy for Stage III dMMR Colon Cancer.” October 12, 2026. 
7. National Comprehensive Cancer Network (NCCN). NCCN Guidelines for Patients: Rectal Cancer, 2026. nccn.org/patients. 

The post FDA Approval: Dostarlimab (Jemperli) for dMMR/MSI-H Locally Advanced Rectal Cancer: What Patients Need to Know appeared first on Fight Colorectal Cancer.

Mike Davis, Research Advocate, Fight CRC

As a survivor of early-onset colorectal cancer (EOCRC), you are used to the questions. Why did this happen to me? Could I have done something to prevent it? How could I have caught it earlier? Why did I survive, when others did not? Why aren’t there more options for my treatment? Why did no one talk to me about quality of life issues caused by treatment? And perhaps most important from the advocate perspective – what will it take to keep others from experiencing what I have experienced?  

Questions like these are what compelled me to become a colorectal cancer research advocate where I had the opportunity to attend the Western Colorectal Cancer Consortium Conference (WC4) in early October. It was inspiring and reassuring to be among researchers and physicians working passionately to answer questions like these that matter to patients and caregivers. Among the many insights of the conference, a few stood out as particularly meaningful to people affected by EOCRC. 

Attendees heard a call to action from Dr. Samir Gupta of UC San Diego about the need to respond to increasing EOCRC rates with “innovative, disruptive translational research.” Survivors and caregivers could interpret this as a plea to researchers for out-of-the-box, and ambitious research ideas that have a real-world ability to quickly change outcomes for early-onset patients. We should all be encouraged that this message is being delivered directly to those who have the capacity and expertise to reverse the EOCRC trends we see today. 

Dr. Joshua Demb, also of UC San Diego, shared insights into ways that healthcare providers could improve detection of EOCRC. Although many physicians are concerned about rising incidence in younger people, detecting EOCRC can be like finding a needle in a haystack. Dr. Demb shared research on red flag signs and symptoms that could help clinicians “make a smaller haystack.” He also presented ways that other countries like Denmark and the U.K. have created so-called “urgent cancer pathways” for timely diagnosis of EOCRC. The U.S. lags behind its peers in quickly diagnosing EOCRC patients after high-risk symptoms are identified. However, alternative models for more rapid detection of EOCRC already exist, and advocates could focus their efforts on seeing these models applied here in the U.S. 

EOCRC patients and caregivers commonly share the perspective that advancements in treatment options for colorectal cancer lag significantly behind the advances made in other cancers. However, Dr. Heinz Josef Lenz of USC presented on immunotherapy advancements in colorectal cancer that encourage us to be hopeful about the future of immunotherapy for EOCRC patients. In particular, he noted progress on immunotherapy treatments for microsatellite-stable metastatic disease, the subtype of colorectal cancer responsible for approximately 95% of all metastatic colorectal cancers, and which has been very resistant to immuno-oncology approaches so far. 

Finally, Dr. Katherine Van Loon of UC San Francisco shared the blueprint and early lessons from UCSF’s newly opened Young-Onset Colorectal Cancer Clinic in San Francisco. Intended to provide tailored care for the EOCRC population, Dr. Van Loon emphasized a particular focus on exercise programming aimed at reducing cancer recurrence and specialized services for fertility planning, two topic areas of high importance to the EOCRC population.  

Overall, I found lots of reasons to be hopeful about the future of colorectal cancer prevention, detection, treatment, and survivorship, and am already looking forward to representing Fight CRC at next year’s conference. However, these advancements in detection, treatment, and survival will surely not come fast enough for the EOCRC community. That’s why it’s important to continue representing the patient and caregiver experience in venues like WC4. By adding human faces and stories to the data and trials researchers and physicians are working on we hope we can lend an urgency and gravity to the stakes of early-onset colorectal cancer research.  

The post Western Colorectal Cancer Consortium Conference – Perspectives from an Early Onset Colorectal Cancer Survivor appeared first on Fight Colorectal Cancer.

Fam Cancer. 2026 Oct 20;25(4):97. doi: 10.1007/s10689-026-00598-5.

ABSTRACT

Lynch syndrome, one of the most common hereditary cancer predisposition syndromes, is caused by pathogenic variants in the mismatch repair genes (MLH1, MSH2, MSH6, PMS2) and the EPCAM gene. Individuals who inherit pathogenic variants in Lynch-associated genes experience increased lifetime risk of colorectal, endometrial, and several other cancer types. Risks of Lynch-associated cancers vary by the affected gene and within each gene, especially for lower penetrance genes. This poses challenges for clinicians to provide patients and families with accurate cancer risk estimates and determine individualized surveillance protocols. Compounding this challenge is that study designs and potential biases could yield different risk estimates. In this review, we present up-to-date Lynch syndrome cancer risk estimates and discuss how study design could impact these risk estimates.

PMID:42900270 | DOI:10.1007/s10689-026-00598-5

The post Updated cancer risks in lynch syndrome appeared first on Fight Colorectal Cancer.

J Natl Cancer Inst. 2026 Oct 19:djag217. doi: 10.1093/jnci/djag217. Online ahead of print.

ABSTRACT

BACKGROUND: Large-scale proteomics may reveal circulating biomarkers of colorectal cancer (CRC) years before diagnosis, yet cross-cohort reproducibility and anatomic site-specificity remain unclear.

METHODS: We conducted nested case-control studies in three prospective cohorts with banked blood and cancer follow-up (median 7 years), totaling 851 incident CRC cases matched 1:1 to controls, with 1,801 pre-diagnostic plasma proteins from Olink panels.

RESULTS: Twelve proteins showed significant paired differences between CRC cases and controls (FDR <0.1), with modest effect sizes. These included previously implicated CRC-biomarkers (e.g., higher GDF15 and TFF2) as well as less established associations (e.g., lower LEPR and BCAN). Paired protein differences are significantly distinct in colon vs. rectal cancer pairs (P = 0.005), driven by genes enriched in leukocyte activation, cell activation, and extracellular components. In stratified analysis, for colon cancer, 11 out of 12 proteins were lower in cases (FDR <0.1), including BCAN with 0.83 (0.74-0.94) odds ratio (OR, with 95% CI) per 1-unit increase in quantile-normalized NPX level, with cross-cohort consistency (I2 <0.01). For rectal cancer, 25 out of 28 proteins were higher in cases, including HDGF (OR 1.75 [1.15-2.66], I2 <0.01). HDGF could partially mediate BMI-rectal cancer risk (25.0%, FDR=0.044). Overall, we found that pre-diagnostic plasma proteomics identified proteins and pathways with modest effect sizes and clear differences between future risk of colon and rectal cancer.

CONCLUSION: These findings provide insight for future mechanistic validation of pre-diagnostic plasma proteins as CRC biomarkers and motivate site-specific biomarker discovery that distinguishes colon from rectal cancer.

PMID:42895287 | DOI:10.1093/jnci/djag217

The post Identification of prediagnostic proteomic biomarkers for colon and rectal cancer in 3 prospective cohorts appeared first on Fight Colorectal Cancer.

Clinical Trials Roundup

This month, we’re spotlighting five clinical trials. Three focus on life after surgery, including new options for patients who are ctDNA-positive after treatment and immunotherapy for dMMR colon cancer. Two offer new options for cancer that has progressed. Plus, a bonus Phase 3 trial to keep on your radar. These summaries are written to help you start informed conversations with your care team. 

Need help understanding clinical trials or biomarker testing? See our resources — or ask ChatCRC, Fight CRC’s AI tool, to help make sense of your biomarker report or find trials matched to your diagnosis. 

October 2026

1. TTX-MC138: Targeting a Driver of Metastasis in ctDNA-Positive Colorectal Cancer 

Biomarker Focus: ctDNA-positive minimal residual disease (MRD) after curative-intent therapy 
Phase / Sites: Phase II (PRE-I-SPY platform) / U.S. sites recruiting in Birmingham, Alabama (University of Alabama at Birmingham); Chicago, New Lenox, and Orland Park, Illinois; and Minneapolis, Minnesota 
Stage: Stage I–III colon or rectal cancer; standard curative-intent therapy completed; ctDNA-positive with no visible disease on scans 
Recruitment Status: Recruiting (platform-wide; confirm the colorectal cohort is open at your nearest site) 
What It’s Studying: This study tests TTX-MC138, an investigational treatment designed to block microRNA-10b, a molecule believed to help cancer cells spread and survive. It enrolls people whose ctDNA blood test shows signs of remaining cancer, even though their scans are clear. TTX-MC138 is given by IV once every four weeks for up to 12 cycles, and the study plans to enroll up to 45 patients. 
Why It Matters: Patients who are ctDNA-positive after finishing treatment have a higher risk of recurrence but few proven options. This trial tests a different idea: targeting a driver of metastasis before cancer becomes visible. The evidence is early. An earlier Phase 1 study in 16 patients with various advanced cancers was designed mainly to test safety, and this study will be the first to test whether the drug works in this colorectal cancer setting. 
Patient Tip: If your scans are clear but a ctDNA test came back positive, ask your care team: “Are there trials designed for people in my situation, and is one available near me?” 
Provider Tip: To qualify, you’ll need a tumor-informed ctDNA test, one built from your own tumor tissue, that shows signs of remaining cancer after you’ve finished treatment, while your scans stay clear. Before you plan any travel, ask your care team to confirm that the colorectal cancer group is enrolling at the site nearest you. 
ClinicalTrials.gov: NCT05868226 

2. AMB-05X: Retraining the Immune Environment After Treatment for ctDNA-Positive Colorectal Cancer 

Biomarker Focus: ctDNA-positive minimal residual disease (MRD) after curative-intent therapy 
Phase / Sites: Phase II / MD Anderson Cancer Center, Houston, Texas 
Stage: Stage I–IV colorectal cancer; all planned curative-intent therapy completed with no evidence of disease; ctDNA-positive with no visible disease on scans 
Recruitment Status: Recruiting 
What It’s Studying: This study tests AMB-05X, an investigational treatment that targets CSF1R on macrophages, immune cells that can help tumors grow when they are “reprogrammed” by cancer. The main goal is to see how many patients clear ctDNA from their blood after six months of treatment. The study plans to enroll about 15 patients. 
Why It Matters: This is the another ctDNA-positive trial at MD Anderson, but uses a very different approach than the TAS-102 study. Instead of chemotherapy, it targets the immune environment around hidden cancer cells. It also accepts patients with stage IV disease who had no evidence of disease after curative treatment, a group often left out of MRD trials. 
Patient Tip: If you’ve completed treatment for stage I to IV colorectal cancer, including surgery to remove metastases, and a ctDNA test is positive, ask: “Am I eligible for an MRD trial even though my cancer was stage IV?” 
Provider Tip: Timing matters here. Your positive ctDNA test needs to come at least four weeks after you’ve completed all of your planned treatment, and your scans need to be clear. If you’ve had a positive result, bring the report to your next visit so your care team can check whether it meets the study’s requirements. 
ClinicalTrials.gov: NCT06617858 

3. AZUR-2: Immunotherapy Before and After Surgery for dMMR Colon Cancer 

Biomarker Focus: Deficient mismatch repair (dMMR) / MSI-H 
Phase / Sites: Phase III / global multicenter (GSK-sponsored), with U.S. sites in more than 20 states 
Stage: Untreated, resectable T4N0 or stage III colon cancer 
Recruitment Status: Recruiting 
What It’s Studying: AZUR-2 compares dostarlimab, an immunotherapy, given before and after surgery, against standard care: surgery followed by chemotherapy (FOLFOX or CAPEOX) or observation. Participants are randomly assigned, with two out of three receiving dostarlimab. The main goal is event-free survival. 
Why It Matters: This month, the FDA approved the first immunotherapy for use after surgery in stage III dMMR colon cancer, given alongside chemotherapy. AZUR-2 asks the next question: can immunotherapy alone, started before surgery, replace chemotherapy for these patients? For people hoping to avoid chemotherapy side effects, this is one of the most important open questions in early-stage CRC. 
Patient Tip: Timing is everything. This trial is for people who have not yet had surgery. If you’ve just been diagnosed with colon cancer, ask your care team before surgery is scheduled: “Has my biopsy been tested for MMR or MSI status, and could I qualify for an immunotherapy trial before surgery?” 
Provider Tip: The time to ask about this trial is before your surgery is scheduled. Ask your care team to check your biopsy for MMR or MSI status as early as possible. If your tumor is dMMR, you may have options that start before surgery. Let your care team know if you’ve had a stent placed for a blockage, since that can affect eligibility. 
ClinicalTrials.gov: NCT05855200 

4. PROCEADE-CRC-03: A New Antibody-Drug Conjugate for Previously Treated Metastatic Colorectal Cancer 

Biomarker Focus: No biomarker selection required (targets CEACAM5, a protein found on most colorectal cancers) 
Phase / Sites: Phase III / about 165 sites in 20 countries, including U.S. community cancer centers in Colorado, Florida, Illinois, Michigan, Minnesota, Missouri, New York, Tennessee, Texas, and Virginia 
Stage: Stage IV metastatic colorectal cancer; previously treated, with no more than two prior regimens for metastatic disease 
Recruitment Status: Recruiting 
What It’s Studying: This Phase III trial compares precemtabart tocentecan, an investigational antibody-drug conjugate (ADC), given alone or with bevacizumab, against a current standard option, trifluridine/tipiracil plus bevacizumab. ADCs work like a guided delivery system: an antibody finds a protein on cancer cells (here, CEACAM5) and delivers chemotherapy directly to them. The study is for patients previously treated with irinotecan, oxaliplatin, a fluoropyrimidine, and bevacizumab, and its main goal is longer overall survival. 
Why It Matters: Options narrow after second-line treatment, and current later-line therapies shrink tumors in only a small share of patients. In the earlier Phase 1 study, about one in four patients who had already received irinotecan saw their tumors shrink at the dose now being tested, though not all of those responses had been confirmed when the results were reported. This Phase III will show whether that early signal translates into longer survival. This is a large randomized trial at community cancer centers, so many patients may be able to enroll closer to home. 
Patient Tip: If your cancer has progressed after one or two lines of treatment for metastatic disease, ask your care team: “Is there a site near me for PROCEADE-CRC-03, and would I qualify based on the treatments I’ve already had?” 
Provider Tip: Bring a list of every treatment you’ve had for metastatic disease. This trial is for people who have already received irinotecan, oxaliplatin, a fluoropyrimidine like 5-FU or capecitabine, and bevacizumab, and who have had no more than two treatment regimens since their cancer spread.  
ClinicalTrials.gov: NCT07549412 

5. KANDLELIT-001: Calderasib + Cetuximab for Previously Treated KRAS G12C Colorectal Cancer 

Biomarker Focus: KRAS G12C mutation 
Phase / Sites: Phase I / multinational, with U.S. sites including Moffitt Cancer Center (Tampa, Florida), START Midwest (Grand Rapids, Michigan), and Hackensack, New Jersey, plus additional sites in New York, Virginia, and Wisconsin 
Stage: Locally advanced unresectable or metastatic colorectal cancer; one to two prior systemic therapies 
Recruitment Status: Recruiting  

What It’s Studying: KANDLELIT-001 is the first-in-human study of calderasib (MK-1084), a next-generation KRAS G12C inhibitor. The colorectal cancer group tests calderasib with cetuximab, an anti-EGFR antibody, in patients whose cancer has progressed after one or two prior treatments. 
Why It Matters: This is the study whose early results led to the Phase 3 KANDLELIT-012 trial, which is testing calderasib earlier, as first-line treatment. KANDLELIT-001 offers access to the same drug for patients who have already been through treatment. Results in colorectal cancer were presented in 2026. 
Patient Tip: Not all KRAS mutations are the same. If your biomarker report says “KRAS-mutated,” ask: “Which KRAS mutation do I have? If it’s G12C, am I eligible for this trial or KANDLELIT-012?” 
Provider Tip: Make sure your biomarker report names your exact KRAS mutation. This trial requires KRAS G12C specifically, confirmed by a tissue or blood test, and is for people who have had one or two prior treatments for advanced cancer. If you’ve already taken a KRAS G12C inhibitor, tell your care team, since that may affect whether you qualify.  

ClinicalTrials.gov: NCT05067283 

Keep On Your Radar: COMPASSION-40, Cadonilimab Before and After Surgery for dMMR Colon Cancer 

Biomarker Focus: Deficient mismatch repair (dMMR) / MSI-H 
Phase / Sites: Phase III / sponsored by Akeso (China-based) 
Stage: Resectable MSI-H/dMMR colon cancer 
Recruitment Status: Recruiting (first patient dosed October 2026) 
What It’s Studying: COMPASSION-40 tests cadonilimab, an investigational immunotherapy that blocks two immune checkpoints (PD-1 and CTLA-4) in a single molecule, given alone before and after surgery. 
Why It Matters: In an earlier Phase II study, most patients who received cadonilimab before surgery had no remaining cancer found at the time of surgery. That study was small, so this Phase 3 trial is designed to test whether those results hold up. Cadonilimab is approved in China for other cancers but not in the U.S. 
Patient Tip: This trial may not be available in the U.S., but it’s one to watch alongside AZUR-2. If you have newly diagnosed dMMR colon cancer, ask your care team about U.S. immunotherapy trials before surgery. 
ClinicalTrials.gov: NCT07412613 

Disclaimer: Inclusion in this roundup does not imply endorsement or guaranteed benefit. Always consult your healthcare provider to determine whether a clinical trial is appropriate for you. Recruitment status is current as of publication and subject to change. Verify current status at ClinicalTrials.gov before making any treatment decisions. 

September 2026

1. Denikitug (GS-1811) Alone or in Combination: A New TIGIT-Targeting Approach for MSS Colorectal Cancer 

Biomarker Focus: Microsatellite stable (MSS) / proficient mismatch repair (pMMR) metastatic CRC 
Phase / Sites: Phase II / 14 sites including Yale, Dana-Farber, Beth Israel Deaconess, Washington University, University of Virginia, Avera Cancer Institute (U.S.) and Australia 
Stage: Advanced, unresectable, or metastatic CRC; up to 2 prior lines of therapy 
Recruitment Status: Recruiting 
What It’s Studying: This Phase II trial evaluates denikitug (GS-1811), a Gilead-sponsored investigational antibody targeting TIGIT, an immune checkpoint that helps tumors evade the immune system. The study tests denikitug alone, combined with nivolumab (anti-PD-1), and combined with trifluridine-tipiracil plus bevacizumab in MSS metastatic CRC patients who have received up to two prior lines of therapy. 
Why It Matters: MSS colorectal cancer accounts for roughly 85–90% of all metastatic cases and has largely been excluded from the immunotherapy advances seen in MSI-H/dMMR disease. TIGIT is a distinct checkpoint target, separate from PD-1 and CTLA-4, and blocking it may help unlock immune responses in tumors that currently resist checkpoint therapy. This is the first Phase II TIGIT-targeting trial specifically designed for MSS CRC with multiple combination arms, representing a genuinely new research direction for the largest group of patients who lack immunotherapy options today. 
Patient Tip: If your tumor is MSS or pMMR and you’ve received one or two prior chemotherapy regimens, ask your oncologist: ‘Are there trials targeting TIGIT or other new immune checkpoints that I might qualify for?’ MSS does not mean immunotherapy is off the table; it means the approach needs to be different, and trials like this one are building that path. 
Provider Tip: If you’ve received one or two prior chemotherapy regimens and your tumor is MSS, you may be eligible for this trial — but timing matters. Make sure your care team knows your full treatment history, including whether you’ve received trifluridine-tipiracil, regorafenib, or fruquintinib, as these can affect which arm of the study you qualify for. Sites at major cancer centers including Dana-Farber and Washington University may be worth asking about if travel is an option. 
ClinicalTrials.gov: NCT07527858

2. Balstilimab + Botensilimab + agenT-797: Combining Cell Therapy and Immunotherapy for MSS CRC With Liver Metastases 

Biomarker Focus: MSS / pMMR metastatic CRC with liver metastases 
Phase / Sites: Phase II / 1 U.S. site: Scripps Clinic Torrey Pines, La Jolla, California 
Stage: Metastatic CRC with liver involvement; ≥1 prior line including fluorouracil, oxaliplatin, and irinotecan 
Recruitment Status: Recruiting 
What It’s Studying: This investigator-sponsored Phase II trial at Scripps Health tests a three-drug combination: balstilimab (anti-PD-1), botensilimab (Fc-enhanced anti-CTLA-4), and agenT-797, an allogeneic invariant natural killer T (iNKT) cell therapy. The study specifically enrolls patients with MSS metastatic CRC that has spread to the liver, a population with historically lower immunotherapy response rates because the liver microenvironment actively suppresses immune activity. Patients must have at least one measurable liver lesion and no prior immunotherapy. 
Why It Matters: Three-year BOT/BAL survival data from ESMO GI 2026 generated significant interest, but that dataset largely excluded patients with active liver metastases, a common and clinically important scenario in metastatic CRC. This trial adds agenT-797, an off-the-shelf iNKT cell therapy, to the BOT/BAL backbone to ask whether cellular therapy can help break through the liver’s immune resistance. It is the first trial to combine iNKT cell therapy with dual checkpoint blockade specifically for MSS CRC with liver involvement. 
Patient Tip: If your cancer has spread to the liver and your tumor is MSS, conversations about immunotherapy may have felt discouraging. This trial is asking whether adding a cellular therapy on top of dual checkpoint blockade can change that equation. The single California site may not be accessible to everyone, but asking your oncologist about trials combining cell therapy with immunotherapy for MSS liver-involved disease may open doors to similar options.
ClinicalTrials.gov: NCT07550088

3. TAS-102 for ctDNA-Positive Minimal Residual Disease: Testing Whether Treatment Can Erase ‘Hidden’ Cancer After Surgery 

Biomarker Focus: ctDNA-positive minimal residual disease (MRD) after curative-intent surgery and adjuvant chemotherapy 
Phase / Sites: Phase II / MD Anderson Cancer Center, Houston, Texas 
Stage: Stage II, III, or IV; R0 resected, curative-intent therapy completed, ctDNA-positive with no radiographic disease 
Recruitment Status: Recruiting 
What It’s Studying: This MD Anderson Phase II trial tests whether trifluridine-tipiracil (TAS-102), an oral chemotherapy, can clear circulating tumor DNA (ctDNA) from the blood of colorectal cancer patients who have finished curative-intent surgery and at least three months of oxaliplatin-based adjuvant chemotherapy. Eligible patients must have a positive ctDNA test with no visible tumor on imaging, a state researchers call minimal residual disease (MRD). The primary goal is measuring how many patients achieve ctDNA clearance at six months. 
Why It Matters: Positive ctDNA after surgery is one of the strongest signals of recurrence risk in CRC, often detectable months before anything shows on a scan. But detecting it raises an urgent question the field hasn’t yet answered: if we find it, can we treat it? This is one of the first trials to test an active therapeutic intervention for ctDNA-positive MRD in CRC, rather than surveillance alone. A positive result could reshape post-surgical care for a high-risk group that currently has no clear treatment standard.
Patient Tip: If you have finished surgery and chemotherapy, your scans are clear, but you’ve heard about ctDNA testing, this trial speaks directly to your situation. Ask your care team: ‘Has my ctDNA been tested, and if it’s positive, are there trials designed to treat what’s left behind?’ Not all centers routinely offer ctDNA testing after surgery, so asking specifically is an important first step. 
Provider Tip: If your scans are clear after surgery and chemotherapy but a ctDNA test has come back positive, this trial may be an option worth discussing. Ask your care team whether your ctDNA result was confirmed through a CLIA-certified lab — Signatera is the preferred assay for enrollment. This trial is at MD Anderson in Houston, so it requires travel, but for patients who want to act on a positive ctDNA result rather than wait, it’s a conversation worth having.
ClinicalTrials.gov: NCT05343013

4. Adjuvant Toripalimab: Immunotherapy After Surgery for High-Risk dMMR/MSI-H Colon Cancer 

Biomarker Focus: Deficient mismatch repair (dMMR) / MSI-H; Stage IIB, IIC, or III colon cancer 
Phase / Sites: Phase II / 5 Emory network sites, Atlanta, Georgia (NCI-sponsored) 
Stage: Localized; Stage IIB, IIC, or III colon cancer, R0 resected 
Recruitment Status: Recruiting 
What It’s Studying: This Emory/NCI Phase II trial tests toripalimab, an anti-PD-1 immunotherapy, as a standalone adjuvant treatment for patients with high-risk dMMR/MSI-H colon cancer following complete resection. Participants receive eight doses over six months, with a primary endpoint of three-year disease-free survival. Unlike the ATOMIC trial (featured in Fight CRC’s January 2026 Roundup), which added immunotherapy to adjuvant chemotherapy, this study tests immunotherapy alone, asking whether the dMMR biology of these tumors makes a chemotherapy-free approach both effective and better tolerated. 
Why It Matters: For dMMR patients, the question of whether immunotherapy can replace — not just add to — post-surgical chemotherapy is one of the most patient-relevant open questions in CRC. Many patients in this situation are motivated to avoid chemotherapy side effects if biology supports it. This trial also tracks patient-reported outcomes alongside efficacy data, meaning results will speak to quality of life, not just survival, which matters deeply to newly operated patients weighing their next step.
Patient Tip: If you’ve just had surgery for Stage IIB, IIC, or III colon cancer and your tumor is MSI-H or dMMR, you may be in an enrollment window for this trial. The window is narrow: four to twelve weeks after surgery — so the conversation needs to happen soon. Ask your care team before starting adjuvant chemotherapy: ‘Am I a candidate for an immunotherapy-only trial after surgery?
Provider Tip: If you’ve just had surgery for dMMR or MSI-H colon cancer, the window to enroll in this trial is four to twelve weeks post-surgery, so bring it up with your oncologist at your first post-operative visit, before any adjuvant treatment decisions are made. Make sure your pathology report confirms dMMR or MSI-H status, and let your care team know if you received any treatment before surgery, as this may affect eligibility.
ClinicalTrials.gov: NCT07140679

5. The PUMP Trial: Hepatic Arterial Infusion Pump Chemotherapy for Unresectable Colorectal Liver Metastases 

Biomarker Focus: No specific biomarker requirement; liver-confined unresectable colorectal cancer metastases (excludes MSI-H) 
Phase / Sites: Phase III / 62 U.S. sites across ~20 states, including MSK, Mayo Clinic, Northwestern, Duke, Emory, UT Southwestern, Ohio State, Fox Chase, Vanderbilt, and more (ECOG-ACRIN / NCI-sponsored) 
Stage: Stage IV; unresectable colorectal liver metastases, liver-confined disease, after 3–6 months of first-line chemotherapy with stable or responding disease 
Recruitment Status: Recruiting 
What It’s Studying: The PUMP Trial is a randomized Phase III study comparing standard systemic chemotherapy alone against systemic chemotherapy plus hepatic arterial infusion (HAI), a surgically implanted pump that delivers floxuridine chemotherapy directly into the liver’s blood supply. Sponsored by ECOG-ACRIN and the NCI, the trial enrolls patients with colorectal cancer that has spread only to the liver and cannot be surgically removed, who have stable or responding disease after completing three to six months of first-line chemotherapy. The primary endpoint is overall survival. 
Why It Matters: HAI pump chemotherapy is FDA-approved and has shown strong results at high-volume centers like Memorial Sloan Kettering, but it remains underused nationally, largely because most patients never hear about it. By delivering chemotherapy directly into the liver’s arterial supply, HAI achieves much higher drug concentrations at the tumor site than systemic chemotherapy alone can reach. The PUMP Trial is the largest randomized effort to define whether adding HAI to modern systemic therapy can extend survival, and its 62 U.S. sites make it one of the most geographically accessible trials in this Roundup. 
Patient Tip: If your colorectal cancer has spread to the liver and your doctors have said surgery isn’t currently possible, ask specifically: ‘Am I a candidate for a hepatic arterial infusion pump, and is the PUMP Trial available near me?’ HAI is not widely offered outside of specialized centers, so many patients who could benefit simply don’t know to ask. With sites at major cancer centers across the country, access to this trial is broader than most.
Provider Tip: Key eligibility: liver-confined unresectable CRC confirmed by multidisciplinary review, stable/responding disease after 3-6 months of first-line chemotherapy, no prior HAI or FUDR, no prior liver-directed therapy (TACE, TARE), no MSI-H disease, ECOG 0–1, liver tumor burden ≤70%. CT angiography confirming acceptable hepatic arterial anatomy is required within 4 weeks of randomization. With 62 active U.S. sites, the PUMP Trial is the most geographically accessible trial in this month’s Roundup and worth a proactive referral conversation for liver-confined metastatic CRC patients. 
ClinicalTrials.gov: NCT05863195

Disclaimer: Inclusion in this roundup does not imply endorsement or guaranteed benefit. Always consult your healthcare provider to determine whether a clinical trial is appropriate for you. Recruitment status is current as of publication and subject to change. Verify current status at ClinicalTrials.gov before making any treatment decisions. 

August 2026

1. Symbiotic-GI-03 — A Clinical Trial Researching a Potential Combination Treatment for People With Metastatic Colorectal Cancer

Phase / Sites: Phase III / ~210 sites worldwide
Stage: Stage IV metastatic colorectal adenocarcinoma
Recruitment Status: Recruiting
What it’s studying: Pfizer’s Phase 3 double-blind clinical trial is evaluating a potential first-line treatment for patients with metastatic colorectal cancer who have not received prior anticancer treatment for metastatic disease. The study medicine, PF-08634404, is an investigational bispecific antibody that targets both PD-1 (an immune checkpoint) and VEGF (a protein that supports tumor blood vessel growth) at the same time. It is thought that by binding to these proteins, the study medicine may help the immune system find and attack the cancer cells while also potentially slowing tumor growth. Participants will receive either the study medicine in combination with chemotherapy, or bevacizumab, in combination with chemotherapy.
Why it matters: Bevacizumab combined with chemotherapy remains a common first-line standard treatment for colorectal cancer, but outcomes are still limited. Most colorectal cancers, especially those that are not MSI-H/dMMR, do not respond to immunotherapy alone. This clinical trial is researching whether the study medicine combination may improve progression-free survival (PFS) and overall survival (OS) compared to the bevacizumab combination.
Patient Tip: If you are diagnosed with metastatic colorectal cancer and have not yet started treatment, ask your doctor whether a first-line clinical trial such as Symbiotic-GI-03 may be an option for you. It is recommended that your tumor has been tested for key biomarkers, including RAS, BRAF V600E, and MSI/dMMR, as these results may help determine your eligibility for this clinical trial and others. 
ClinicalTrials.gov: NCT07222800  |  www.PfizerStudyforCRC.com 

2. INCA033890-303 — Chemotherapy + Bevacizumab With or Without INCA33890 in First-Line MSS Metastatic CRC 

Biomarker Focus: Microsatellite stable (MSS) / mismatch repair proficient (pMMR) metastatic CRC; excludes MSI-H/dMMR and BRAF V600E 
Phase / Sites: Phase III / Multicenter, including U.S. sites (Incyte-sponsored) 
Stage: Stage IV metastatic colorectal adenocarcinoma, first-line 
Recruitment Status: Recruiting 
What it’s studying: INCA033890-303 is a Phase 3 randomized, double-blind study comparing standard first-line chemotherapy plus bevacizumab with or without INCA33890, an investigational bispecific antibody targeting both PD-1 and TGFβR2 (transforming growth factor beta receptor 2). The trial enrolls patients with MSS metastatic CRC who have not previously received systemic treatment for metastatic disease. 
Why it matters: MSS colorectal cancer accounts for the large majority of metastatic cases and has historically been resistant to immunotherapy. A key reason is that TGF-beta signaling in the tumor environment actively suppresses the immune response. INCA33890 is designed to address this by blocking TGFβR2 specifically on immune cells that also express PD-1, a more targeted approach than prior TGF-beta inhibitors that caused significant toxicity. Along with Symbiotic-GI-03 and HARMONi-GI3, it is one of only three Phase 3 trials currently seeking to change how MSS mCRC is treated in the first line. 
Patient Tip: MSS is the most common biomarker profile in metastatic CRC, and historically it has meant fewer immunotherapy options. If that sounds like your diagnosis, it’s worth asking your oncologist whether this trial is available near you before you begin standard treatment. The eligibility window is first-line only, so the conversation needs to happen before chemotherapy starts. 
ClinicalTrials.gov: NCT07284849 

3. ROSETTA CRC-203 — Pumitamig + Chemotherapy vs. Bevacizumab + Chemotherapy in First-Line Metastatic CRC 

Biomarker Focus: First-line mCRC without dMMR, MSI-H, or BRAF V600E (broad MSS/RAS population)
Phase / Sites: Phase II/III / Global multicenter, including U.S. sites (Bristol-Myers Squibb / BioNTech) 
Stage: Stage IV unresectable or metastatic colorectal cancer, first-line 
Recruitment Status: Recruiting 
What it’s studying: ROSETTA CRC-203 is evaluating pumitamig, an investigational bispecific antibody targeting both PD-L1 and VEGF-A, in combination with standard chemotherapy compared against bevacizumab plus chemotherapy in patients with previously untreated, unresectable or metastatic CRC without dMMR, MSI-H, or BRAF V600E. Early Phase 2 data presented at ASCO 2026 showed promising activity, and the study is now enrolling its Phase 3 registrational cohort. 
Why it matters: Pumitamig targets PD-L1 rather than PD-1, which some researchers believe may have advantages in the tumor microenvironment of MSS CRC. The ASCO 2026 interim data generated significant interest, and enrollment into the Phase 3 portion represents an early opportunity for patients to access a drug that has not yet completed its pivotal trial. 
Patient Tip: There’s a lot happening in first-line CRC research right now, and it can feel overwhelming to keep up. Here’s a simple question worth bringing to your next appointment: ‘Are there any trials testing new combinations in first-line treatment that I might qualify for?’ Asking early, before treatment begins, is the only way to know if something like ROSETTA CRC-203 is an option for you. 
ClinicalTrials.gov: NCT07221357

4. MOUNTAINEER-03 — Tucatinib + Trastuzumab + mFOLFOX6 in HER2-Positive First-Line Metastatic CRC 

Biomarker Focus: HER2-positive, RAS wild-type first-line mCRC 
Phase / Sites: Phase III / 50+ sites globally, including U.S. 
Stage: Stage IV metastatic CRC, first-line 
Recruitment Status: Recruiting 
What it’s studying: MOUNTAINEER-03 is testing whether adding tucatinib and trastuzumab, a dual HER2-targeting combination, to standard first-line chemotherapy improves outcomes for the roughly 4% of metastatic CRC patients with HER2-amplified, RAS wild-type tumors. This Phase 3 trial compares tucatinib plus trastuzumab plus mFOLFOX6 against the current standard of care. 
Why it matters: HER2-targeted therapy has already shown meaningful benefit in patients with HER2-positive CRC who have progressed on prior lines of treatment. MOUNTAINEER-03 asks whether starting HER2 targeting earlier, at the very first line of metastatic treatment, can extend those benefits further. If positive, it would establish a new first-line standard for this biomarker subgroup. 
Patient Tip: HER2 testing is not always automatically included when you’re first diagnosed. If you’ve gotten biomarker results back and aren’t sure whether HER2 was checked, ask specifically. It’s a simple question with a potentially significant answer, especially if you’re RAS wild-type. Your care team can order the test, and it takes the guesswork out of knowing which trials you might qualify for. 
ClinicalTrials.gov: NCT05253651

5. FRUITFUL — Fruquintinib + FOLFIRI as Second-Line Treatment for Metastatic CRC 

Biomarker Focus: MSS/pMMR mCRC without BRAF V600E; prior oxaliplatin, fluoropyrimidine, and bevacizumab in first line 
Phase / Sites: Phase II / 14 U.S. sites across 9 states (SCRI-sponsored) 
Stage: Stage IV metastatic CRC, second-line 
Recruitment Status: Recruiting 
What it’s studying: FRUITFUL is a Phase II study evaluating fruquintinib, an FDA-approved oral VEGFR inhibitor, in combination with FOLFIRI chemotherapy as second-line treatment for patients with metastatic CRC. Participants must have completed first-line oxaliplatin, fluoropyrimidine, and bevacizumab-based therapy. The study is testing whether adding fruquintinib to the standard second-line FOLFIRI backbone can improve outcomes for patients progressing after first-line treatment. 
Why it matters: Fruquintinib is already FDA-approved as a later-line monotherapy for mCRC, but this trial explores whether its anti-angiogenic mechanism works even better when combined with chemotherapy earlier in the treatment sequence. For patients who have finished first-line therapy and are planning their next step, this is a meaningful opportunity to access a novel combination at a critical transition point. Sites span nine states, making this one of the more geographically accessible trials currently enrolling. 
Patient Tip: If you’ve just finished first-line treatment and your cancer has progressed, this might be exactly the kind of trial worth asking about at your next appointment. The eligibility is fairly straightforward: prior oxaliplatin-based chemo plus bevacizumab, no prior irinotecan. You don’t need a specific biomarker result to qualify, which makes it one of the more accessible trials for a broader group of patients right now. 
ClinicalTrials.gov: NCT07011576

July 2026 

1. OrigAMI-1 — Amivantamab Alone or With Chemotherapy in Chemorefractory RAS/BRAF Wild-Type Metastatic CRC 

Biomarker Focus: RAS/BRAF wild-type and HER2 non-amplified metastatic CRC; tumor sidedness evaluated 
Phase / Sites: Phase Ib/II / International multicenter, including U.S. sites 
Stage: Advanced or metastatic CRC, two to three prior lines of therapy 
Recruitment Status: Active, ongoing (combination chemotherapy cohorts) 
What it’s studying: OrigAMI-1 is the foundational study evaluating amivantamab, a bispecific antibody targeting both EGFR and MET, alone or combined with mFOLFOX6 or FOLFIRI chemotherapy in patients with RAS/BRAF wild-type metastatic CRC after two to three prior lines of therapy. 
Why it matters: Updated results at ASCO GI 2026 showed over 70% of patients in the first-line combination chemotherapy subgroup responded, with most responses lasting beyond 16 months; results that launched two pivotal phase 3 studies now enrolling (OrigAMI-2 and OrigAMI-3, below). 
Patient Tip: If you have RAS/BRAF wild-type CRC and have been through several lines of treatment, ask your care team whether early-phase trials studying newer EGFR-targeting combinations are still open to enrollment.
ClinicalTrials.gov: NCT05379595 

2. OrigAMI-2 — Amivantamab + Chemotherapy vs. Cetuximab + Chemotherapy in First-Line Left-Sided RAS/BRAF Wild-Type Metastatic CRC 

Biomarker Focus: RAS/BRAF wild-type (KRAS, NRAS, and BRAF all wild-type); left-sided primary tumor 
Phase / Sites: Phase III / Global multicenter, including U.S. sites 
Stage: Unresectable or metastatic colorectal cancer, first-line 
Recruitment Status: Recruiting 
What it’s studying: OrigAMI-2 is comparing amivantamab plus chemotherapy (mFOLFOX6 or FOLFIRI) versus cetuximab plus chemotherapy as first-line treatment for patients with left-sided, RAS/BRAF wild-type metastatic CRC. 
Why it matters: Anti-EGFR therapy with chemotherapy is already the standard for this group, but resistance develops in most patients. Data from ESMO GI 2026 showed liquid biopsy can track that resistance; OrigAMI-2 is testing whether targeting both EGFR and MET from the start delays it. 
Patient Tip: If your tumor is RAS/BRAF wild-type and left-sided, ask your care team whether there are first-line trials testing a next-generation EGFR-targeting approach before starting standard treatment. 
ClinicalTrials.gov: NCT06662786

3. OrigAMI-3 — Amivantamab + FOLFIRI vs. Cetuximab or Bevacizumab + FOLFIRI in Second-Line RAS/BRAF Wild-Type Metastatic CRC 

Biomarker Focus: RAS/BRAF wild-type (KRAS, NRAS, and BRAF all wild-type) metastatic CRC 
Phase / Sites: Phase III / Global multicenter, including U.S. sites (Fox Chase Cancer Center, UCLA, and others) 
Stage: Recurrent, unresectable, or metastatic CRC after first-line chemotherapy 
Recruitment Status: Recruiting 
What it’s studying: OrigAMI-3 is evaluating subcutaneous amivantamab plus FOLFIRI versus standard second-line treatment (cetuximab or bevacizumab plus FOLFIRI) in patients with RAS/BRAF wild-type metastatic CRC who progressed on first-line chemotherapy. 
Why it matters: MET amplification is a known mechanism by which CRC develops resistance to anti-EGFR therapy after first-line treatment; amivantamab targets both EGFR and MET, and phase 1b/2 data from ASCO GI 2026 showed promising activity even in patients with prior anti-EGFR exposure. 
Patient Tip: If you have RAS/BRAF wild-type CRC and your cancer progressed on first-line therapy, ask your care team whether a second-line trial targeting both EGFR and MET could be right for you. 
ClinicalTrials.gov: NCT06750094

4. Botensilimab + Balstilimab + Fasting Mimicking Diet + Vitamin C for KRAS-Mutant MSS Metastatic CRC 

Biomarker Focus: KRAS-mutant, microsatellite stable (MSS) metastatic colorectal cancer 
Phase / Sites: Phase Ib / University of Southern California (Los Angeles, CA) 
Stage: Metastatic colorectal cancer after prior fluoropyrimidine, oxaliplatin, and irinotecan 
Recruitment Status: Recruiting 
What it’s studying: This study evaluates botensilimab and balstilimab combined with a fasting mimicking diet (a structured, plant-based, low-calorie eating plan) and high-dose intravenous vitamin C in patients with KRAS-mutant MSS metastatic CRC. 
Why it matters: ESMO GI 2026 featured three-year survival data for botensilimab plus balstilimab in MSS CRC; this trial explores whether adding metabolic strategies can extend that benefit to patients with KRAS mutations, who make up a large share of MSS metastatic CRC cases. 
Patient Tip: If your tumor is MSS and has a KRAS mutation, ask your care team whether trials combining immunotherapy with nutritional or metabolic strategies are available to you. 
ClinicalTrials.gov: NCT06336902

 5. Botensilimab + Balstilimab + SBRT for MSS CRC With Liver Metastases 

Biomarker Focus: Non-MSI-H or mismatch repair proficient (pMMR) colorectal cancer with liver metastases 
Phase / Sites: Pilot study / Massachusetts General Hospital (Boston, MA) 
Stage: Metastatic colorectal cancer with liver metastases 
Recruitment Status: Recruiting 
What it’s studying: This study evaluates botensilimab and balstilimab combined with stereotactic body radiation therapy (SBRT) to liver metastases in patients with MSS or pMMR CRC, asking whether precisely targeted radiation can activate an immune response in a setting where immunotherapy alone has been harder to get to work. 
Why it matters: The three-year ESMO GI 2026 BOT/BAL data came from patients without active liver metastases; liver involvement is associated with lower immunotherapy response rates in MSS CRC, and this trial directly addresses that gap. 
Patient Tip: If your cancer has spread to the liver, ask your care team whether trials combining radiation with newer immunotherapy drugs are available at your treatment center. 
ClinicalTrials.gov: NCT07128355 

June 2026

1. HARMONi-GI3 — Ivonescimab + mFOLFOX6 in First-Line Metastatic Colorectal Cancer

Biomarker Focus: Metastatic colorectal cancer; immunotherapy and VEGF pathway strategy
Phase / Sites: Phase III / Multicenter
Stage: Metastatic colorectal cancer
Recruitment Status: Recruiting
What It’s Studying:
This study compares ivonescimab plus mFOLFOX6 chemotherapy with bevacizumab plus mFOLFOX6 for patients who have not yet received systemic treatment for metastatic CRC.
Why It Matters:
First treatment decisions can feel urgent and overwhelming. This trial is studying whether combining chemotherapy with a treatment that targets both immune response and tumor blood-vessel growth may offer another first-line approach.
Patient Tip:
Ask your care team: “Do I know my MSI/MMR status, and are there any first-line clinical trials that match my diagnosis and treatment goals?”
ClinicalTrials.gov: NCT07228832

2. BAY 3771249 — KRAS G12D-Targeted Therapy for Advanced or Metastatic CRC

Biomarker Focus: KRAS G12D mutation
Phase / Sites: Phase I / Multicenter
Stage: Advanced or metastatic colorectal cancer
Recruitment Status: Recruiting
What It’s Studying:
This study is evaluating BAY 3771249, an investigational treatment being studied alone or with cetuximab for patients with advanced or metastatic CRC that has a KRAS G12D mutation.
Why It Matters:
KRAS G12D has limited targeted treatment options. This trial reflects the growing effort to develop therapies based on the exact KRAS mutation driving a person’s cancer.
Patient Tip:
Ask your care team: “Do I have a KRAS G12D mutation, and are there trials designed specifically for this subtype?”
ClinicalTrials.gov: NCT07535112

3. SGN-CEACAM5C — Antibody-Drug Conjugate Targeting CEACAM5

Biomarker Focus: CEACAM5 expression
Phase / Sites: Phase I / International study with U.S. sites
Stage: Advanced solid tumors, including colorectal cancer cohorts
Recruitment Status: Recruiting
What It’s Studying:
This study is evaluating SGN-CEACAM5C, also known as PF-08046050, in adults with advanced solid tumors, including CRC cohorts. Antibody-drug conjugates are designed to deliver treatment more directly to cancer cells with a specific target.
Why It Matters:
When standard treatments stop working, patients often want to know what other options are being studied. This trial is one example of research exploring more targeted approaches for advanced CRC.
Patient Tip:
Ask your care team: “Has my tumor been tested for markers that could help match me to a targeted therapy or antibody-drug conjugate trial?”
ClinicalTrials.gov: NCT06131840

4. EMPIRE / NSABP FC-13 — Immunotherapy for ctDNA-Positive Minimal Residual Disease

Biomarker Focus: ctDNA-positive minimal residual disease after colorectal cancer treatment
Phase / Sites: Phase II / Multicenter
Stage: Colorectal cancer after definitive surgery and chemotherapy, with ctDNA positivity
Recruitment Status: Recruiting
What It’s Studying:
EMPIRE is studying cemiplimab alone or with other immunotherapy-based treatments for people with CRC who are ctDNA-positive after surgery and chemotherapy. ctDNA is tumor DNA that can sometimes be detected through a blood test.
Why It Matters:
Many patients want to know what ctDNA results may mean for recurrence risk and next steps. This study is asking whether immunotherapy-based treatment can help delay or prevent colorectal cancer from coming back in patients with ctDNA-positive minimal residual disease.
Patient Tip:
If you have completed surgery and chemotherapy, ask your care team: “Is ctDNA testing appropriate for me, and would a positive result change my follow-up plan or clinical trial options?”
ClinicalTrials.gov: NCT07058012

5. KANDLELIT-012 — Calderasib (MK-1084) + Cetuximab + mFOLFOX6 for KRAS G12C-Mutated Colorectal Cancer

Biomarker Focus: KRAS G12C mutation
Phase / Sites: Phase III / Multicenter
Stage: Locally advanced unresectable or metastatic colorectal cancer
Recruitment Status: Recruiting
What It’s Studying:
This study is evaluating calderasib, also known as MK-1084, with cetuximab and mFOLFOX6 chemotherapy compared with mFOLFOX6 with or without bevacizumab in KRAS G12C-mutated CRC.
Why It Matters:
KRAS mutations are common in CRC, but not all KRAS mutations are the same. This trial focuses on KRAS G12C and reflects the movement toward treatments matched to specific tumor biomarkers.
Patient Tip:
If your care team says your tumor has a KRAS mutation, ask: “Which KRAS mutation do I have, and does that specific result make me eligible for any clinical trials?”
ClinicalTrials.gov: NCT06997497

6. Bonus Research Watch: CRDF-004 — Onvansertib + Chemotherapy and Bevacizumab for RAS-Mutated Metastatic Colorectal Cancer

Biomarker Focus: KRAS or NRAS mutation
Phase / Sites: Phase II / U.S. multicenter study
Stage: First-line metastatic colorectal cancer
Recruitment Status: Active, not recruiting
What It’s Studying:
CRDF-004 is studying onvansertib with standard chemotherapy and bevacizumab for adults with metastatic CRC that has a KRAS or NRAS mutation.
Why It Matters:
RAS mutations are common in metastatic CRC, and researchers continue to look for better first-line strategies. This trial is not currently recruiting, but it remains important to watch because ASCO 2026 featured interim results from CRDF-004 in first-line RAS-mutated metastatic CRC.
Patient Tip:
If your tumor has a KRAS or NRAS mutation, ask your care team: “Are there current or upcoming trials for RAS-mutated colorectal cancer that may fit my treatment plan?”
ClinicalTrials.gov: NCT06106308

May 2026

1. NCI ComboMATCH — Combination Therapy Based on Tumor Genetics 

Biomarker Focus: Actionable genetic alterations 
Phase / Sites: Screening trial supporting multiple Phase II treatment sub-studies  / U.S. NCI network 
Stage: Advanced solid tumors, including colorectal cancer when biomarker eligible 
Recruitment Status: Recruiting 
What it’s studying: ComboMATCH assigns patients to treatment combinations based on tumor genetic changes rather than cancer type alone, using a screening platform that matches patients to specific sub-studies. 
Why it matters: This builds on precision medicine by testing whether targeted drug combinations can improve outcomes for patients whose tumors have actionable alterations. 
Patient Tip: If you’ve had genomic testing, ask whether your results include an alteration that could match to a precision medicine trial. 
ClinicalTrials.gov: NCT05564377 
 

2. BASECAMP-1 — Screening Study for Future CEA-Targeted Cell Therapy 

Biomarker Focus: CEA expression, HLA type (including HLA loss of heterozygosity), tumor immune markers 
Phase / Sites: Observational screening study / U.S. sites 
Stage: Solid tumors, including colorectal cancer 
Recruitment Status: Recruiting 
What it’s studying: BASECAMP-1 screens patients for biomarkers that may determine eligibility for future CEA-targeted cell therapy studies. 
Why it matters: This expands biomarker testing beyond tumor mutations to include immune matching and cell therapy eligibility. 
Patient Tip: If you’re interested in cell therapy trials, ask whether HLA typing or CEA testing could be relevant. 
ClinicalTrials.gov: NCT04981119 

3. Onvansertib Combination Trial — KRAS-Mutant Metastatic Colorectal Cancer 

Biomarker Focus: KRAS mutation 
Phase / Sites: Phase II / U.S. and international sites 
Stage: Metastatic colorectal cancer 
Recruitment Status: Active, Not Recruiting 
What it’s studying: This study evaluates onvansertib with standard chemotherapy and bevacizumab in patients with KRAS-mutant metastatic colorectal cancer. 
Why it matters: KRAS mutations are common in CRC, but many KRAS-mutant tumors still lack effective targeted options. This study focuses on a biologically defined CRC group. 
Patient Tip: If your tumor has a KRAS mutation, ask whether the specific KRAS variant and prior treatments affect trial eligibility. 
ClinicalTrials.gov: NCT06106308 
 

4. P-MUC1C-ALLO1 — Allogeneic CAR-T Cell Therapy Targeting MUC1-C 

Biomarker Focus: MUC1-C expression 
Phase / Sites: Phase I / Includes U.S. sites 
Stage: Advanced or metastatic solid tumors, including colorectal cancer 
Recruitment Status: Active, Not Recruiting 
What it’s studying: This study evaluates an allogeneic CAR-T cell therapy targeting MUC1-C, a tumor-associated marker expressed in several epithelial cancers. 
Why it matters: Cell therapy research in CRC is expanding, and biomarker testing may help identify patients whose tumors express targets like MUC1-C. 
Patient Tip: Ask whether your tumor testing includes protein-expression markers, not just DNA mutations. 
ClinicalTrials.gov: NCT05239143 

5. GCC19CART — CAR-T Therapy Targeting GCC in Advanced Gastrointestinal Cancers 

Biomarker Focus: GCC / guanylyl cyclase C expression 
Phase / Sites: Phase I / U.S. sites 
Stage: Metastatic colorectal cancer 
Recruitment Status: Recruiting 
What it’s studying: This trial evaluates CAR-T cells targeting GCC, a marker commonly associated with colorectal cancer cells. 
Why it matters: GCC-targeted cell therapy is a CRC-relevant biomarker strategy and represents a newer research direction for patients with advanced disease. 
Patient Tip: If you are exploring cell therapy options, ask whether your tumor expresses GCC or whether a GCC-targeted study is available. 
ClinicalTrials.gov: NCT05319314 

April 2026

1. JANUS Rectal Cancer Trial — Total Neoadjuvant Therapy in Locally Advanced Rectal Cancer 
Biomarker Focus: Response-adapted treatment and organ preservation strategy 
Phase / Sites: Phase II / U.S. cooperative group, multicenter 
Stage: Stage II-III / locally advanced rectal cancer 
Recruitment Status: Active, not recruiting 
What it’s studying: JANUS is comparing long-course chemoradiation followed by mFOLFIRINOX versus mFOLFOX6 to improve clinical complete response and organ preservation in locally advanced rectal cancer. 
Why it matters: This study is relevant right now because it focuses on treatment intensification and organ-preservation goals in rectal cancer—an area of strong interest for patients and clinicians alike. 
Patient Tip: If you are discussing treatment before rectal cancer surgery, ask whether total neoadjuvant therapy or organ-preservation strategies may be appropriate for you. 
ClinicalTrials.gov: NCT05610163 

2. EA2201 — Immunotherapy in dMMR Stage II/III Rectal Cancer 
Biomarker Focus: Deficient mismatch repair (dMMR) / MSI-H 
Phase / Sites: Phase II / Multicenter U.S. trial 
Stage: Stage II–III locally advanced rectal adenocarcinoma 
Recruitment Status: Active, not recruiting 
What it’s studying: EA2201 is evaluating nivolumab + ipilimumab with short-course radiation in patients with MSI-H/dMMR rectal cancer, with the goal of improving response while potentially reducing the need for more intensive conventional treatment. 
Why it matters: dMMR rectal cancer is one of the clearest examples of biomarker-driven care in CRC. This trial reflects the shift toward tailoring treatment based on tumor biology. 
Patient Tip: If your tumor is dMMR or MSI-H, ask whether immunotherapy-based trials may be available before surgery. 
ClinicalTrials.gov: NCT04751370 

3. COMMIT Study — First-Line Immunotherapy Strategy in Metastatic dMMR/MSI-H Colorectal Cancer 
Biomarker Focus: dMMR / MSI-H 
Phase / Sites: Phase III / national multicenter trial 
Stage: Metastatic colorectal cancer 
Recruitment Status: Active, not recruiting 
What it’s studying: COMMIT is testing atezolizumab-based first-line treatment strategies, including chemotherapy/bevacizumab-containing approaches, in metastatic dMMR CRC. 
Why it matters: Although immunotherapy is already important in dMMR/MSI-H CRC, not all patients have durable benefit. COMMIT is trying to refine the best first-line approach for this population. 
Patient Tip: If you have metastatic dMMR/MSI-H CRC and are starting treatment, ask whether a first-line immunotherapy trial is an option. 
ClinicalTrials.gov: NCT02997228 

4. ERAS-007 Combination Trial in Advanced Gastrointestinal Malignancies, Including Colorectal Cancer 
Biomarker Focus: MAPK pathway / BRAF and RAS pathway signaling 
Phase / Sites: Phase Ib/II / Multicenter, including U.S. sites 
Stage: Advanced gastrointestinal malignancies, including metastatic CRC 
Recruitment Status: Completed 
What it’s studying: This study is evaluating ERAS-007, an ERK inhibitor, in combination regimens designed to interrupt downstream MAPK signaling in GI cancers, including CRC. 
Why it matters: Many CRC tumors are driven by pathway alterations that remain difficult to target directly. ERAS-007 reflects a newer strategy aimed at blocking downstream signaling to improve outcomes. 
Patient Tip: If your cancer has a BRAF or RAS-pathway alteration, ask whether downstream pathway-targeting trials may be appropriate. 
ClinicalTrials.gov: NCT05039177 

5. Nous-209 Vaccine Prevention Study in Lynch Syndrome 
Biomarker Focus: Lynch syndrome / mismatch repair deficiency risk 
Phase / Sites: Phase Ib/II / U.S.-based prevention study 
Stage: High-risk individuals with Lynch syndrome 
Recruitment Status: Active, not recruiting 
What it’s studying: This study is evaluating the Nous-209 vaccine strategy for cancer prevention in Lynch syndrome carriers at elevated risk for colon and other Lynch-associated cancers. 
Why it matters: This is a prevention-focused trial rather than a treatment trial, but it is highly relevant to colorectal cancer because it aims to reduce future cancer risk in a well-defined high-risk population. 
Patient Tip: If you or your family members have Lynch syndrome, ask whether prevention studies or surveillance-focused research may be appropriate. 
ClinicalTrials.gov: NCT05078866 

March 2026

1. ARPA-H ADAPT Oncology Platform – Colorectal Cohort 

Biomarker Focus: Real-time biomarker integration and adaptive trial infrastructure 
Phase / Sites: Early research initiative / United States 
Stage: Colorectal cancer (see eligibility criteria in protocol) 
Recruitment Status: Not yet recruiting 
What it’s studying: This ARPA-H supported initiative is part of the ADAPT oncology platform, designed to modernize how cancer clinical trials are conducted. The platform integrates advanced biomarker monitoring, coordinated data systems, and adaptive treatment strategies to accelerate therapeutic development in CRC and other cancers. 
Why it matters: Rather than testing a single drug, this national investment focuses on transforming the clinical trial system itself — potentially speeding up how promising treatments move from concept to clinic. 
Patient Tip: Even if enrollment hasn’t begun, ask your care team about upcoming federally funded research programs that may open new opportunities. 
ClinicalTrials.gov: NCT07318389

2. Molecularly Guided Therapy Based on Tumor Genetics: NCI-MATCH 

Biomarker Focus: Actionable genetic mutations 
Phase / Sites: Phase 2 / Nationwide (NCI-sponsored) 
Stage: Advanced solid tumors, including colorectal cancer 
Recruitment Status: Active, not recruiting 
What it’s studying: NCI-MATCH assigns treatment based on specific genetic mutations found in a tumor rather than the cancer’s location in the body. Patients with colorectal cancer whose tumors harbor actionable mutations may be matched to targeted therapies designed for those alterations. 
Why it matters: This national precision-medicine trial helped redefine how we think about treatment selection. Instead of a one-size-fits-all approach, MATCH reflects a shift toward therapy guided by tumor biology. 
Patient Tip: If you’ve had comprehensive genomic testing, ask whether your tumor’s mutations may qualify you for a MATCH sub-study. 
ClinicalTrials.gov: NCT02465060

3. COBRA Trial: ctDNA-Guided Predictor in Stage IIA 

Biomarker Focus: Circulating tumor DNA (ctDNA) 
Phase / Sites: Phase 2/3 / U.S. cooperative groups 
Stage: Stage II colon cancer 
Recruitment Status: Active 
What it’s studying: The COBRA study evaluates whether ctDNA testing after surgery can identify patients who truly need chemotherapy and who may safely avoid it. 
Why it matters: This study reflects the growing role of blood-based biomarkers in guiding adjuvant therapy, with the goal of reducing overtreatment while maintaining excellent outcomes. 
Patient Tip: If you have stage II colon cancer, ask whether ctDNA testing is appropriate for you and whether participation in a biomarker-guided trial is an option. 
ClinicalTrials.gov: NCT04068103

4. SWOG S2107: Immunotherapy Strategies in MSS Metastatic CRC 

Biomarker Focus: Microsatellite stable (MSS) and BRAF V600E mutation 
Phase / Sites: Phase 2 / National cooperative group (SWOG) 
Stage: Previously treated metastatic colorectal cancer 
Recruitment Status: Recruiting 
What it’s studying: This study is testing whether adding nivolumab (immunotherapy) to encorafenib + cetuximab improves outcomes in BRAF V600E/MSS metastatic CRC. 
Why it matters: Approximately 85–90% of colorectal cancers are MSS. Expanding immunotherapy strategies for this population remains one of the most urgent research priorities in CRC, and to a population that historically does not benefit from single-agent checkpoint inhibitors. 
Patient Tip: If you’ve been told your tumor is MSS and that immunotherapy alone is unlikely to work, ask whether combination immunotherapy trials are available at your treatment center. 
ClinicalTrials.gov: NCT04963283 

5. CIRCULATE-US (NRG-GI008) — ctDNA-Guided Adjuvant Strategy in Stage II/III 

Biomarker Focus: Circulating tumor DNA (ctDNA) 
Phase / Sites: Phase II/III / North America (NRG Oncology) 
Stage: Stage II and III (resected) colon cancer 
Recruitment Status: Recruiting 
What it’s studying: This randomized study evaluates whether post-surgical ctDNA testing can guide escalation or de-escalation of chemotherapy in patients with stage II or III colon cancer. Patients who test ctDNA-positive may receive intensified therapy, while those who test ctDNA-negative may receive less intensive treatment. 
Why it matters: ctDNA is emerging as a precision tool to detect minimal residual disease and personalize adjuvant therapy decisions. 
Patient Tip: If you’ve had surgery for stage II or III colon cancer, ask whether ctDNA testing or enrollment in a ctDNA-guided trial is appropriate for you. 
ClinicalTrials.gov: NCT05174169 

February 2026

1. BRAFTOVI® + Cetuximab + FOLFIRI — New Triplet Regimen for BRAF V600E mCRC

Biomarker Focus: BRAF V600E mutation
Phase / Sites: Phase 2 / Multinational (Pfizer-sponsored)
Stage: Metastatic (mCRC)
Recruitment Status: Active, not recruiting
What it’s studying: This study evaluates the combination of encorafenib + cetuximab + FOLFIRI in patients with previously treated, BRAF V600E-mutated metastatic CRC.
Findings: Results from ASCO GI 2026 show a significant increase in overall response rates (ORR) and progression-free survival compared to historical controls.
Why it matters: Offers a promising targeted therapy option earlier in the treatment journey for patients with BRAF-mutant CRC.
Patient Tip: If your tumor is BRAF V600E-positive and you’ve been previously treated, ask your care team about this combination.
ClinicalTrials.gov: NCT04607421

2. CIRCULATE-North America (NRG-GI008) — ctDNA-Guided Adjuvant Therapy in Stage II/III CRC

Biomarker Focus: Circulating tumor DNA (ctDNA)
Phase / Sites: Phase II/III / North America (NRG Oncology)
Stage: Stage II and III (resected)
Recruitment Status: Recruiting
What it’s studying: This randomized trial evaluates whether ctDNA testing after surgery can guide the need for adjuvant chemotherapy in patients with stage II or III colon cancer. Patients with detectable ctDNA may receive intensified treatment, while ctDNA-negative patients may avoid unnecessary chemotherapy.
Presented: ASCO GI 2026
Why it matters: ctDNA is emerging as a precision tool for assessing minimal residual disease (MRD). This trial could help patients avoid overtreatment—or identify recurrence risk earlier.
Patient Tip: If you’ve had surgery for stage II or III colon cancer, ask if ctDNA testing might inform your follow-up care plan.
ClinicalTrials.gov: ASCO Abstract: NRG-GI008

3. KEYNOTE-975 Subanalysis — Pembrolizumab in dMMR/MSI-H mCRC

Biomarker Focus: dMMR / MSI-H
Phase / Sites: Phase 3 / Global
Stage: Metastatic
Recruitment Status: Ongoing
What it’s studying: Examining the efficacy of pembrolizumab as a first-line treatment for dMMR/MSI-H metastatic CRC.
Findings: Durable responses reported in previously untreated patients, including those with comorbidities and older age groups.
Why it matters: Validates immunotherapy as a frontline option in dMMR CRC—not just for ideal candidates.
Patient Tip: If your tumor is MSI-H or dMMR, ask if you qualify for first-line immunotherapy.
ClinicalTrials.gov: NCT04003636

4. BEACON-Lite Cohort A — Real-World Evaluation of Triplet Therapy in BRAF CRC

Biomarker Focus: BRAF V600E mutation
Phase / Sites: Phase 2 / Expanded access
Stage: Metastatic
Recruitment Status: Closed to new participants
What it’s studying: A cohort evaluating encorafenib + cetuximab + chemotherapy in patients not eligible for the original BEACON trial.
Findings: Preliminary real-world data shows efficacy in older patients and those with comorbidities.
Why it matters: Supports more inclusive criteria for accessing promising triplet regimens.
Patient Tip: If you were previously excluded from BRAF-targeted trials, ask if real-world data may now support this approach.
ClinicalTrials.gov: NCT02928224

January 2026

1. BREAKWATER Trial — Triplet Therapy Sets New Standard for BRAF V600E mCRC

Biomarker Focus: BRAF V600E mutation
Phase / Sites: Phase 3 / Multi-national
Stage: Stage IV (metastatic)
Recruitment Status: Completed (Phase 3)
What it’s studying: Encorafenib + cetuximab + FOLFIRI vs chemotherapy in first-line mCRC
Findings: PFS nearly doubled (12.8 vs 7.1 months); OS improved to 30.3 vs 15.1 months
Why it matters: A new triplet could replace chemo as the standard for BRAF-mutated mCRC
Patient Tip: If you have BRAF V600E-mutant CRC and are starting first-line treatment, ask whether this triplet regimen is being considered.
ClinicalTrials.gov: N/A

2. ATOMIC Trial — Atezolizumab + Chemo in Stage III dMMR CRC

Biomarker Focus: Mismatch repair deficiency (dMMR / MSI-H)
Phase / Sites: Phase 3 / Multi-center
Stage: Stage III (resected)
Recruitment Status: Completed
What it’s studying: mFOLFOX6 with or without atezolizumab after surgery in stage III colon cancer
Findings: 3-year disease-free survival improved to 86.4% vs 76.6%
Why it matters: May change adjuvant therapy for early-stage dMMR CRC
Patient Tip: If your tumor is MSI-H/dMMR and you’re receiving adjuvant chemo, ask whether immunotherapy was considered or studied in your care setting.
ClinicalTrials.gov: NCT02912559

3. IVX037 + Sintilimab in MSS CRC — RNA Virus Therapy for IO-Resistant Tumors

Biomarker Focus: Microsatellite stable (MSS), KRAS mutations
Phase / Sites: Phase 1 / Single site (expansion)
Stage: Stage IV (refractory)
Recruitment Status: Expansion underway (Phase 1a complete)
What it’s studying: A bio-selected, receptor-targeted oncolytic RNA virus (IVX037) injected into tumors, combined with anti-PD-1 sintilimab
Findings: Disease control in patients with MSS and KRAS G12D CRC; early immune activation observed
Why it matters: One of the first intratumoral viral therapies showing benefit in MSS CRC: a population typically unresponsive to immunotherapy
Patient Tip: If your tumor is MSS and you’ve exhausted chemo options, ask your care team about clinical trials exploring novel immunotherapy combinations or virus-based therapies.
ClinicalTrials.gov: N/A

4. DYNAMIC-III Trial — ctDNA-Guided Escalation in Stage III CRC

Biomarker Focus: Circulating tumor DNA (ctDNA)
Phase / Sites: Phase 2 / Australia
Stage: Stage III (resected)
Recruitment Status: Completed
What it’s studying: Use of post-surgical ctDNA to guide chemotherapy intensity
Findings: Escalation based on ctDNA positivity improved outcomes; negative ctDNA patients avoided unnecessary chemo
Why it matters: Further validates ctDNA as a tool for adjuvant therapy decisions
Patient Tip: If you’ve had surgery for stage III CRC, ask if ctDNA testing could help tailor your chemotherapy plan.
ClinicalTrials.gov: NCT03803553

5. Tumor-Agnostic ADC Use in CRC – Real-World Data on KRAS G12C and HER2+ Subtypes
Biomarker Focus: KRAS G12C, HER2, and ADC-responsive profiles
Phase / Sites: Retrospective / Multiple centers
Stage: Stage IV (refractory)
Recruitment Status: Retrospective analysis of real-world patients (not an interventional trial)
What it’s studying: Outcomes among CRC patients treated with tumor-agnostic antibody-drug conjugates (ADCs) in third-line or later settings
Findings: HER2+ and KRAS G12C patients experienced stable disease or prolonged progression-free survival with investigational ADCs
Why it matters: Highlights the transition of novel ADCs from trials to practice and underscores the importance of biomarker matching in refractory mCRC
Patient Tip: If you’ve already tried standard treatments, ask your provider about biomarker testing for targets like HER2 or KRAS G12C, which may open access to novel ADC-based strategies through expanded access or real-world use.
ClinicalTrials.gov: N/A

The post On Our Radar: October 2026 Clinical Trials Roundup appeared first on Fight Colorectal Cancer.

BMC Gastroenterol. 2026 Oct 12;26(1):641. doi: 10.1186/s12876-026-05422-z.

ABSTRACT

BACKGROUND: Low-dose aspirin use is associated with reduced CRC incidence and CRC-related mortality. A similar association with P2Y12 inhibitor use remains uncertain. We investigated whether the use of P2Y12 inhibitors was associated with CRC incidence and CRC-related mortality among individuals diagnosed with atherosclerotic cardiovascular disease (ASCVD).

METHODS: From the ESPRESSO cohort, we identified 334,882 patients diagnosed with ASCVD between 2006 and 2021. We identified patients who initiated P2Y12 inhibitors ≥ 84 consecutive Defined Daily Doses (cDDDs). We estimated the risk of incident CRC and CRC mortality according to P2Y12 inhibitor use using Cox proportional-hazards regression models adjusting for potential confounders including comorbidities and regular aspirin use.

RESULTS: We documented 4,015 incident CRC cases and 2,610 CRC-related deaths during a median follow-up of 5.1 years (IRQ, 2.1-9.0 years). We did not observe an association between P2Y12 inhibitor use and CRC incidence. In contrast, a longer duration of P2Y12 inhibitor use was associated with lower CRC-related mortality. Compared to non-users, multivariable-adjusted hazard ratio (HR) for CRC mortality were 0.73 (95% CI, 0.60-0.89) in patients with 336-671 cDDDs of P2Y12 inhibitor and 0.81 (95% CI, 0.68-0.97) in those with ≥672 cDDDs. Among patients with incident CRC diagnosis, subsequent initiation of P2Y12 inhibitor after CRC diagnosis was associated with significantly lower CRC mortality (HR 0.42; 95% CI, 0.29-0.60).

CONCLUSIONS: P2Y12 inhibitor use was not associated with risk of incident CRC but was significantly inversely associated with CRC mortality, which appeared to be due to improved survival among individuals who initiate P2Y12 inhibitors after CRC diagnosis. These findings merit further study given the observational nature of the analysis and potential for residual confounding.

PMID:42870228 | PMC:PMC13660269 | DOI:10.1186/s12876-026-05422-z

The post Platelet P2Y12 inhibitor use and risk of colorectal cancer incidence and colorectal cancer-related mortality: a Swedish registry-based cohort study appeared first on Fight Colorectal Cancer.