According to results from the CheckMate 8HW, nivolumab plus ipilimumab demonstrated a superior progression-free survival (PFS) across all lines of therapy when compared to nivolumab alone, among patients with microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer.

This phase 3, open-label trial enrolled patients with unresectable or metastatic colorectal cancer and MSI-H/dMMR status who had received ≤1 line of therapy without any prior immunotherapy. Patients were randomized 2-to-2-to-1 to receive nivolumab plus ipilimumab (dual therapy arm), nivolumab alone (monotherapy arm), or chemotherapy with or without targeted therapies. Patients who had received ≥2 prior lines of therapy were randomized on a 1-to-1 basis to either the dual therapy or monotherapy arm.

It has previously been reported that CheckMate 8HW met its dual primary end point of PFS by blinded independent central review between the dual therapy and chemotherapy arms in the first-line setting. These are the first results from the other dual primary end points comparing the PFS between the dual therapy and monotherapy arms across all lines of therapy.

Overall, there were 354 patients randomized to dual therapy and 353 to monotherapy, with 55% and 52% respectively who received the study treatment in the first line. Of the patients randomized, there were 296 in the dual therapy and 286 in the monotherapy arm who had their MSI-H/dMMR status centrally confirmed. With a median follow-up duration of 47 months, the median PFS in the dual therapy group was not reached (95% confidence interval [CI, 53.8 to not estimable) vs 39.3 months in the monotherapy arm (95%CI, 22.1 to not estimable), representing a statistically significant and clinically meaningful improvement (hazard ratio [HR], 0.62; 95% CI, 0.48 to 0.81; P = .0003). Additionally, the dual therapy arm had higher 12-, 24-, and 36-month PFS rates when compared to the monotherapy arm. The objective response rate was significantly higher in the dual therapy arm (71%) vs the monotherapy arm (19%; P = .0011). There were no new safety signals identified.

Dr Andre et al concluded, “These results establish [nivolumab plus ipilimumab] as the potential new standard-of-care treatment for MSI-IH/dMMR [metastatic colorectal cancer].”

Source:

Andre T, Elez E, Lenz, H-J, et al. First results of nivolumab (NIVO) plus ipilimumab (IPI) vs NIVO monotherapy for microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC) from CheckMate 8HW. Presented at the 2025 ASCO Gastrointestinal Cancers Symposium. January 23-25, 2025; San Francisco, CA. Abstract LBA143