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A new bispecific immune checkpoint inhibitor, INCA33890, is showing real promise in microsatellite stable (MSS) colorectal cancer — a subtype that has historically resisted immunotherapy. Phase 1 data presented at the 2026 ESMO Congress showed a 71.4% objective response rate in first-line patients when combined with standard chemotherapy, with no dose-limiting toxicities across any cohort. A phase 3 trial (NEXERA-303) is now enrolling to confirm these results.
Microsatellite stable (MSS) colorectal cancer has long been considered immunotherapy-resistant, but a novel bispecific antibody called INCA33890 may be changing that narrative. Phase 1 data from the INCA33890-101 trial, presented at the 2026 ESMO Congress, showed that INCA33890 — which simultaneously blocks both PD-1 and TGF-β receptor 2 on immune cells — combined with standard-of-care (SOC) chemotherapy was well tolerated and produced meaningful responses across first- and third-line settings, with no dose-limiting toxicities in any cohort.
The drug's bispecific design is key: by targeting TGF-β signaling specifically in PD-1–positive T cells, it aims to reverse immune suppression in the tumor microenvironment without the broad toxicity seen with systemic TGF-β inhibitors. These early results have now paved the way for the randomized, double-blind phase 3 NEXERA-303 trial, which opened in March 2026 and is comparing INCA33890 plus FOLFOX and bevacizumab vs placebo plus FOLFOX and bevacizumab in 700 first-line MSS metastatic CRC patients.
By the Numbers:
Why it matters: If NEXERA-303 is positive, immunotherapy could enter first-line treatment for MSS mCRC for the first time — a potentially practice-changing shift for a patient population with historically limited options.
