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MSS (Immunotherapy Emerging)
Genes Involved
MMR proficient
Treatment Implications
EMERGING: Botensilimab + Balstilimab showing breakthrough activity (ORR 24%, DCR 73% in refractory MSS mCRC). FDA breakthrough therapy designation. Phase 3 trials ongoing. Standard options: Chemotherapy, TAS-102 + Bevacizumab (SUNLIGHT), Fruquintinib (FRESCO-2).
Recommended Treatments
Botensilimab + Balstilimab (clinical trials)
TAS-102 + Bevacizumab
Fruquintinib
Regorafenib
Standard chemotherapy
Treatments to Avoid
No specific contraindications noted
Study References
Botensilimab Phase 1/2, SUNLIGHT (PMID: 37133585), FRESCO-2 (PMID: 37331369)
Key Statistics
85.00%
Prevalence in CRC
Yes
Targetable
Clinical Notes
MSS/pMMR tumors are traditionally resistant to checkpoint inhibitors. Botensilimab is Fc-enhanced anti-CTLA-4 with improved T-reg depletion. First IO showing meaningful activity in MSS CRC. SUNLIGHT established TAS-102 + Bevacizumab as third-line standard (OS 10.8mo).
Information
Category: Immunotherapy
Evidence Level: Level 3
Last Updated: Dec 21, 2025
Medical Disclaimer: This information is for educational purposes only and should not replace professional medical advice. Always consult with your oncologist for personalized treatment decisions based on your specific situation.