Clinical Trials Roundup
Curated by Fight CRC’s Medical Advisory Board & Research Advocacy Training and Support (RATS) team.
This month, we’re spotlighting trials that reflect a growing national investment in colorectal cancer research, and what that means for you. From precision medicine to next-generation trial platforms, these studies are designed to expand options, personalize care, and improve how research works for patients.
Clinical trials don’t just test treatments; they shape the future of care. And staying informed gives you more power in your treatment journey.
Need help understanding clinical trials or biomarker testing? See our biomarker resources here.
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
https://clinicaltrials.gov/study/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
https://clinicaltrials.gov/study/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
https://clinicaltrials.gov/study/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
https://clinicaltrials.gov/study/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
https://clinicaltrials.gov/study/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
