1,077 Colorectal Cancer Clinical Trials Recruiting Now (May 2026): KRAS, MSI, BRAF, HER2, CEACAM5 ADC, Ivonescimab, Cadonilimab, Immunotherapy
Last updated: May 25, 2026
Current Clinical Trial Landscape
Active research areas in 2026:
Immunotherapy for MSS/pMMR tumors (234 trials) — the biggest challenge in CRC: making "cold" tumors respond to immunotherapy via bispecifics, HDACi combos, and novel IO agents
MSI-H/dMMR organ preservation (133 trials) — checkpoint immunotherapy alone achieving complete responses, enabling surgery avoidance for rectal cancer
KRAS-targeted therapy (71 trials) — G12C inhibitors moving to first-line, pan-RAS and G12D inhibitors expanding to the most common CRC mutations
ctDNA-guided adjuvant therapy — multiple Phase 3 trials using liquid biopsy to decide who needs chemo after surgery
ADCs (40 trials) and T-cell engagers entering CRC for the first time
Standard of care:MSI-H/dMMR metastatic: Pembrolizumab or nivolumab+ipilimumab first-line. MSS/pMMR metastatic (RAS/BRAF wild-type, left-sided): FOLFOX or FOLFIRI + cetuximab. MSS/pMMR (right-sided or RAS-mutant): FOLFOX or FOLFIRI + bevacizumab. BRAF V600E: Encorafenib + cetuximab (± binimetinib). KRAS G12C: Sotorasib + panitumumab. HER2+: Tucatinib + trastuzumab. Stage III adjuvant: CAPOX (3 or 6 months) or FOLFOX. Locally advanced rectal: Neoadjuvant chemoradiation → surgery (dMMR: immunotherapy may replace chemoradiation).
Key Biomarkers for Trial Eligibility
Colorectal cancer treatment is highly biomarker-driven. These determine your trial options:
Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR) — present in ~15% of early-stage and ~5% of metastatic CRC. Responds dramatically to checkpoint immunotherapy. dMMR rectal cancer patients may achieve complete response with immunotherapy alone, avoiding surgery entirely.
RAS status (KRAS/NRAS) — mutated in ~50% of CRC. KRAS G12C (~3-4%) has FDA-approved targeted therapy (sotorasib + panitumumab). G12D (~12%) and G12V (~8%) have emerging inhibitors. RAS wild-type patients benefit from anti-EGFR therapy.
BRAF V600E — present in ~8-10%. Aggressive biology, poor prognosis with standard chemo. Encorafenib + cetuximab is FDA-approved. Multiple combination trials recruiting.
HER2 amplification — present in ~3-5% (higher in RAS wild-type). Tucatinib + trastuzumab approved. T-DXd and new ADC trials recruiting.
Tumor sidedness — left-sided (splenic flexure to rectum) vs right-sided (cecum to transverse). Left-sided tumors respond better to anti-EGFR therapy. Right-sided tumors are more often MSI-H and BRAF-mutant.
ctDNA (circulating tumor DNA) — increasingly used post-surgery to detect minimal residual disease. ctDNA-positive patients benefit from adjuvant chemo; ctDNA-negative may safely skip it. Multiple Phase 3 trials are testing this approach.
Know your MSI/MMR status and mutations? Get matched to colorectal cancer trials in minutes.
Checkpoint immunotherapy is transforming treatment for this subset. Trials push IO earlier and explore organ preservation:
Neoadjuvant / organ preservation (rectal):
NCT03051464 - No Surgery Trial: dose-escalation strategies for dMMR rectal cancer (Phase 2/3)
NCT06229041 - TNTi: Total neoadjuvant treatment ± immunotherapy for high-risk locally advanced rectal cancer (Phase 3)
Adjuvant / Neoadjuvant (MSI-H/dMMR specific):
NCT07412613 - Neoadjuvant/adjuvant cadonilimab (AK104) in MSI-H/dMMR resectable colorectal cancer (Phase 3, PD-1 × CTLA-4 bispecific peri-operative)
NCT05236972 - PACE: PD-1 antibody for dMMR/MSI-H stage III colon cancer (Phase 3)
NCT06520683 - Adjuvant PD-1 blockade for high-risk stage II dMMR/MSI-H CRC (Phase 3)
MSS / pMMR — Immunotherapy Combinations (the "cold tumor" challenge)
Most CRCs are MSS and don't respond to IO alone. Trials combine IO with targeted agents, bispecifics, or novel immunomodulators:
NCT07228832 - Ivonescimab or Bevacizumab + FOLFOX in first-line metastatic CRC (Phase 3, head-to-head PD-1/VEGF bispecific vs anti-VEGF backbone)
NCT07152821 - Botensilimab + Balstilimab vs best supportive care in chemo-refractory unresectable CRC (Phase 3, the next-gen Fc-enhanced CTLA-4 + PD-1 combo testing the highest-unmet-need post-chemo MSS setting)
NCT07221357 - Pumitamig (bispecific) + Chemo vs Bevacizumab + Chemo in mCRC (Phase 3)
CRC has been a late ADC entrant relative to breast/lung — 2026 brings the first Phase 3 of a CEACAM5-directed ADC in metastatic CRC:
NCT07549412 - Precemtabart Tocentecan (M9140, CEACAM5 ADC) ± Bevacizumab vs Trifluridine/Tipiracil + Bevacizumab in previously-treated metastatic CRC (Phase 3, the first CEACAM5 ADC to enter Phase 3 in CRC; CEACAM5 is expressed in ~85% of CRC)
Trials by Treatment Setting
Neoadjuvant / Perioperative
NCT06017583 - Neoadjuvant chemo + PD-1 + SIB-IMRT for locally advanced rectal cancer (Phase 3)
NCT05194878 - Neoadjuvant FOLFOXIRI vs immediate surgery for stage II-III colon cancer (Phase 3)
NCT07070622 - OPLAR: Organ preservation for low rectal cancer after neoadjuvant chemo (Phase 3)
Adjuvant (ctDNA-Guided)
Circulating tumor DNA is reshaping adjuvant treatment decisions:
NCT05174169 - Adjuvant chemo based on residual disease evaluation (Phase 3)
NCT06185556 - COLDFIRE-III: IRE and SBRT for perivascular/peribiliary colorectal liver metastases (Phase 3)
NCT05673148 - Total ablative therapy + systemic therapy for limited metastatic CRC (Phase 3)
Novel Approaches
ADCs (~40 trials): Sacituzumab govitecan, new TROP2 and CEACAM5-targeted ADCs entering CRC for the first time (precemtabart tocentecan / M9140 Phase 3, NCT07549412)
How do I find colorectal cancer clinical trials for my biomarkers?
Enter your colorectal cancer details into ClinTrialFinder — including MSI/MMR status, KRAS/NRAS/BRAF mutations, HER2 amplification, tumor sidedness, and prior treatments. The AI matches you with trials based on your specific profile in minutes. No login required.
What colorectal cancer trials are currently recruiting?
There are 1,077 recruiting interventional trials including immunotherapy for MSS tumors (~234, including new Phase 3s: ivonescimab vs bevacizumab + FOLFOX NCT07228832, botensilimab + balstilimab vs BSC in chemo-refractory NCT07152821), MSI-H/dMMR-specific organ preservation and adjuvant trials (~133, including neoadjuvant cadonilimab NCT07412613), EGFR-targeted and EGFR/MET bispecifics (~132), KRAS G12C and pan-RAS inhibitors (~71), BRAF V600E-targeted (~59), HER2-targeted (~38), ADCs (~40, including first-Phase-3-CEACAM5-ADC precemtabart tocentecan NCT07549412), and ctDNA-guided adjuvant trials.
What is the difference between MSI-H and MSS colorectal cancer for clinical trials?
MSI-H/dMMR tumors (~15% of early-stage, ~5% of metastatic CRC) respond dramatically to checkpoint immunotherapy — pembrolizumab alone can be first-line treatment. MSS/pMMR tumors (~85-95%) don't respond to standard immunotherapy, which is why the biggest area of research is finding ways to make MSS tumors respond. Knowing your MSI/MMR status is the most important biomarker for determining your trial options.
What is ctDNA-guided adjuvant therapy?
After surgery for stage II-III colorectal cancer, a blood test (liquid biopsy) can detect tiny amounts of circulating tumor DNA (ctDNA). If ctDNA is positive, it means microscopic cancer remains and adjuvant chemotherapy is likely beneficial. If ctDNA is negative, you may safely skip chemotherapy and its side effects. Multiple Phase 3 trials are testing this approach — it could spare thousands of patients from unnecessary chemo.
Find Colorectal Cancer Trials Matched to Your Situation
Enter your MSI/MMR status, RAS/BRAF mutations, and treatment history to get AI-matched results in minutes.
This page is for information only and is not medical advice. ClinTrialFinder helps you find clinical trials that may match your situation, but enrollment decisions and treatment choices should always be made with your oncologist or healthcare team. Trial eligibility, recruitment status, and treatment details can change — verify directly with the trial sponsor or on ClinicalTrials.gov before acting on any information here.
