Colorectal Cancer Clinical Trials (April 2026): 1,153 Recruiting Interventional Studies

Last updated: April 29, 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
EGFR/MET bispecifics (132 trials) — amivantamab challenging cetuximab/panitumumab as first-line anti-EGFR
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.

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Recruiting Trials by Biomarker

MSI-H / dMMR (133 trials)

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:
- 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 or novel immunomodulators:

NCT07221357 - Pumitamig (bispecific) + Chemo vs Bevacizumab + Chemo in mCRC (Phase 3)
NCT07284849 - SOC Chemo + Bevacizumab ± INCA33890 first-line (Phase 3)
NCT06791512 - mFOLFOX6 + Bevacizumab + PD-1 vs mFOLFOX6 in locally advanced pMMR/MSS CRC (Phase 3)
NCT06280495 - Neoadjuvant Serplulimab + Bevacizumab + FOLFOX vs FOLFOX in RAS/BRAF WT, pMMR/MSS (Phase 3)
NCT06497985 - Tucidinostat (HDACi) + Sintilimab + Bevacizumab in MSS/pMMR mCRC (Phase 3)
NCT06957432 - Node-sparing short-course RT + sequential chemo + PD-1 for MSS rectal cancer (Phase 3)

KRAS-Mutated (71 trials)

KRAS G12C inhibitors are approved. New frontiers: first-line combos, G12D targeting, and pan-RAS:

KRAS G12C first-line:
- NCT06252649 - Sotorasib + Panitumumab + FOLFIRI vs FOLFIRI ± Bevacizumab, first-line mCRC (Phase 3)
- NCT06997497 - Calderasib (MK-1084) + targeted therapy + chemo in CRC (Phase 3, KANDEL)
RAS wild-type:
- NCT06662786 - Amivantamab (EGFR/MET bispecific) + FOLFOX/FOLFIRI vs Cetuximab + FOLFOX/FOLFIRI first-line (Phase 3)
- NCT06750094 - Amivantamab + FOLFIRI vs Cetuximab/Bevacizumab + FOLFIRI in KRAS/NRAS/BRAF WT (Phase 3)

BRAF V600E (59 trials)

Encorafenib + cetuximab is approved. Trials add chemotherapy and IO:

NCT05768178 - DETERMINE: Vemurafenib + Cobimetinib in BRAF+ cancers (Phase 3)

HER2-Amplified (38 trials)

NCT05253651 - Tucatinib + Trastuzumab + mFOLFOX6 vs SOC first-line HER2+ mCRC (Phase 3)

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)
NCT05954078 - ctDNA methylation-guided adjuvant chemo for high-risk stage II/III (Phase 3)
NCT05534087 - Platform study of ctDNA-directed adjuvant chemo in colon cancer (Phase 3)
NCT04089631 - ctDNA-based decision for adjuvant treatment in stage II (Phase 3)
NCT03803553 - Identification and treatment of micrometastatic disease in stage III colon cancer (Phase 3)

Metastatic — Liver-Directed

NCT06857773 - Hepatic arterial infusion pump + systemic therapy for initially unresectable CLM (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
Bispecific antibodies (30 trials): Amivantamab (EGFR/MET), pumitamig, botensilimab — novel approaches to overcome MSS resistance
EGFR/MET bispecifics: Amivantamab challenging cetuximab/panitumumab as first-line anti-EGFR in RAS WT mCRC
ctDNA-guided treatment: Multiple Phase 3 trials using liquid biopsy to personalize adjuvant chemotherapy decisions
Pan-RAS / KRAS G12D: Next-generation inhibitors expanding beyond G12C to cover the most common KRAS mutations in CRC

Showing selected notable trials. View all 1,153 recruiting interventional trials on ClinicalTrials.gov.

Frequently Asked Questions

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 1,153 recruiting interventional trials including immunotherapy for MSS tumors (234), MSI-H/dMMR-specific organ preservation and adjuvant trials (133), EGFR-targeted and EGFR/MET bispecifics (132), KRAS G12C and pan-RAS inhibitors (71), BRAF V600E-targeted (59), HER2-targeted (38), ADCs (40), 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.

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