Curated by Fight CRC’s Medical Advisory Board & Research Advocacy Training and Support (aka RATS) 

Each month, we share a curated list of clinical trials and research findings that may help as you explore treatment options. This month’s focus is on BRAF, KRAS, and MSS (microsatellite stable) biomarkers, which can influence treatment or trial eligibility. While these trials may not be right for everyone or open to new participants, any that seem relevant to your diagnosis could be worth discussing with your care team. 

• Biomarker Focus: BRAF V600E–mutant metastatic CRC
• Recruitment Status: Not recruiting (NCT04607421)
• What It’s Studying: A targeted therapy and chemotherapy combination for newly diagnosed metastatic CRC with BRAF V600E
  Patient Tip: If you have the BRAF V600E mutation, ask your oncologist whether recent results from this trial might apply to your treatment options.
• ClinicalTrials.gov: NCT04607421
• Study Overview (ASCO): Kopetz, S. et al. (2025). Encorafenib, cetuximab and chemotherapy in BRAF-mutant colorectal cancer: a randomized phase 3 trial. Nature Medicine.
  Read The Full Article Here

• Biomarker Focus: Microsatellite Stable (MSS) metastatic CRC
• Recruitment Status: Some studies still recruiting (Search ClinicalTrials.gov by drug names)
• Study Overview: A novel combination of two immune checkpoint inhibitors, sometimes with chemotherapy, for patients with MSS CRC. This includes the first-line BBOPCO trial at Duke and smaller studies combining Botensilimab + Balstilimab with other treatments.
  Patient Tip: If you’ve been told you have MSS CRC and immunotherapy hasn’t been part of your care, this combination might offer a new approach. Ask if you’re eligible for one of the enrolment trials.
• ClinicalTrials.gov: Search Botensilimab OR Balstilimab
• Notable trial: BBOPCO trial (first-line, MSS CRC, at Duke). No centralized link exists—must be searched by drug/trial name.

• Biomarker Focus: KRAS or BRAF mutations (G12C excluded)
• Recruitment Status: Recruiting (NCT06445062)
• What It’s Studying: A multi-target drug that blocks multiple cancer-driving proteins, including KRAS and BRAF
  Patient Tip: If your cancer has a KRAS or BRAF mutation and you’ve already gone through standard therapies, this may be an option to explore—especially if you’re open to early-phase trials.
• ClinicalTrials.gov: NCT06445062
• Study Overview: Jiang, J. et al. (2024). Translational and therapeutic evaluation of RAS-GTP inhibition by RMC-6236 in RAS-driven cancers. Cancer Discovery, 14(6), 994–1010.
  Read the Full Article Here

Advocate Note: KRAS G12D mutations are now a major research focus, with over 16 active U.S. trials as of July 31, 2025. KRAS mutations are found in ~40% of mCRC cases, and KRAS G12D accounts for ~15% of all mCRC. View trials here.

• Biomarker Focus: BRAF Class II/III and other RAF/RAS alterations
• Recruitment Status: Recruiting (NCT06270082)
• What It’s Studying: A targeted therapy that acts as a “molecular glue” to disrupt abnormal signaling in tumors with non-V600E BRAF or RAS mutations
  Patient Tip: If you’ve been told your mutation is “non-V600E” BRAF or a RAS alteration, this might be one of the few trials focused specifically on your tumor type.
• ClinicalTrials.gov: NCT06270082
• Study Overview: Li, J. et al. (2024). Kinase inhibitors and kinase-targeted cancer therapies: recent advances and future perspectives. Int J Mol Sci, 25(10), 5489. Read the Full Article Here

• Biomarker Focus: BRAF V600E–mutant CRC
• Recruitment Status: Recruiting (NCT06102902)
• What It’s Studying: Combines a new epigenetic drug with a known targeted therapy pair to see if it can further improve tumor response
  Patient Tip: If you’ve already tried a targeted BRAF therapy and are looking for next steps, this trial may offer a new approach. It’s early-phase, so ask about safety and eligibility.
• ClinicalTrials.gov: NCT06102902
• Study Overview: Gu, R. et al. (2024). A comprehensive overview of the molecular features and therapeutic targets in BRAFV600E-mutant colorectal cancer. Clin Transl Med.
  Read the Full Article Here

• Biomarker Focus: MSS CRC, possibly BRAF mutation
• Recruitment Status: Not recruiting (NCT03388190)
• What It’s Studying: Combines a short chemotherapy regimen with immunotherapy to see if it improves immune response in MSS patients
  Patient Tip: This trial has completed enrollment, but if you’re MSS and exploring immunotherapy, your oncologist might consider similar strategies based on this trial’s findings.
• ClinicalTrials.gov: NCT03388190
• Study Overview: Ree, A.H. et al. (2024). First-line oxaliplatin-based chemotherapy and nivolumab for metastatic microsatellite-stable colorectal cancer—the randomized METIMMOX trial. Br J Cancer.
  Read the Full Article Here

Disclaimer: Inclusion in this list does not imply endorsement or guaranteed benefit. Always consult your healthcare provider to determine if a clinical trial is appropriate for you.

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