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NewsImmunotherapy may finally be cracking MSS colorectal cancer. Early-phase data for INCA33890, a bispecific antibody targeting both PD-1 and TGF-β receptor 2, showed a 15.2% objective response rate in heavily pretreated patients — including those with liver metastases. These results are now fueling the phase 3 NEXERA-303 trial, which will test the drug alongside standard chemotherapy in the first-line metastatic setting.
Immunotherapy has long struggled in microsatellite stable (MSS) colorectal cancer — a subtype that makes up the vast majority of metastatic CRC cases and has historically resisted checkpoint inhibition. But early data from INCA33890, a novel bispecific antibody, are offering a reason for cautious optimism.
In the phase 1 INCA33890-101 trial, INCA33890 monotherapy achieved a 15.2% objective response rate (ORR) among 105 heavily pretreated MSS CRC patients at recommended expansion doses. Notably, responses were seen even in patients with liver metastases — a group where immunotherapy has been particularly challenging — with an ORR of 12.0% in that subgroup and 23.3% in those without. The drug was generally well tolerated at doses of 900 mg or less every two weeks, with the most common treatment-related adverse effects (fatigue, pruritus, and infusion reactions) occurring at rates below 15%.
These findings are now powering the phase 3 NEXERA-303 trial, which is randomizing patients 1:1 to INCA33890 plus FOLFOX and bevacizumab vs. chemotherapy plus placebo in the first-line metastatic setting, with progression-free survival as the primary endpoint.
By the Numbers:
Why it matters: If NEXERA-303 is positive, it could mark the first time immunotherapy meaningfully moves into first-line treatment for MSS metastatic CRC — a major shift for a population with very limited options.
