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

Last updated: April 2, 2026

Current Clinical Trial Landscape

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

Trial listings from ClinicalTrials.gov. Page summaries generated by AI and may contain errors. Always verify with your healthcare provider.

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