Taiwan FDA Approves Nivolumab/Ipilimumab for MSI-H/dMMR Metastatic CRC

The Taiwan Food and Drug Administration has approved the combination of nivolumab (Opdivo) and ipilimumab (Yervoy) for the treatment of adult patients with unresectable or metastatic colorectal cancer (CRC) that is microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR), according to a press release from ONO Pharma.¹

This regulatory decision expands the use of the dual immunotherapy regimen into the first-line setting for this patient population and converts a previous accelerated approval for second-line use into a full approval for nivolumab monotherapy.

The approval was supported by results from the phase 3 CheckMate 8HW trial (NCT04008030), which were most recently presented at the European Society for Medical Oncology 2025 Congress.² The trial evaluated the efficacy of the combination across multiple treatment lines. The combination of nivolumab and ipilimumab demonstrated a clinically meaningful improvement in progression-free survival (PFS) compared with the investigator’s choice of chemotherapy in patients who had not received prior systemic treatment for metastatic disease.

The median PFS was not reached (NR; 95% CI, 55.2-not estimable [NE]) in the combination arm vs 60.8 months (95% CI, 32.8-NE) in the nivolumab monotherapy arm (HR, 0.69; 95% CI, 0.48-0.99; P = .0413). The prespecified threshold for statistical significance was not met (P <.0383).

The objective response rate was 73% (95% CI, 65%-79%) in the combination arm vs 61% (95% CI, 53%-79%) in the monotherapy arm. Complete responses were noted in 35% vs 31%, partial responses in 37% vs 31%, stable disease in 12% vs 19%, and progressive disease in 11% vs 16%. A descriptive analysis showed that overall survival favored the combination regimen (HR, 0.61; 95% CI, 0.45-0.83).

In previously reported results, the HR for PFS in the first-line setting was 0.21 (95% CI, 0.13-0.35; P <.0001) in favor of the combination over chemotherapy. Furthermore, the trial met its other dual primary end point by demonstrating superior PFS for the combination compared with nivolumab monotherapy across all lines of therapy. In patients with centrally confirmed MSI-H/dMMR status, the HR for PFS was 0.62 (95% CI, 0.48-0.81; P = .0003).

CheckMate 8HW is a global, multi-center, open-label phase 3 study that randomly assigned approximately 830 patients with MSI-H or dMMR metastatic CRC. Patients were assigned to 1 of 3 arms: nivolumab at 240 mg every 3 weeks for 4 doses, then 480 mg every 4 weeks plus ipilimumab at 1 mg/kg every 3 weeks for 4 doses; nivolumab monotherapy at 240 mg every 2 weeks for 6 doses, then 480 mg every 4 weeks; or investigator’s choice of chemotherapy.

The chemotherapy arm consisted of 5-fluorouracil, folinic acid, and oxaliplatin (mFOLFOX6) or 5-fluorouracil, folinic acid, and irinotecan (FOLFIRI), either alone or in combination with bevacizumab (Avastin) or cetuximab (Erbitux). The dual primary end points were PFS per blinded independent central review (BICR) for the combination vs chemotherapy in the first-line setting and PFS per BICR for the combination vs nivolumab monotherapy across all lines of therapy. Patients continued treatment until disease progression or the occurrence of unacceptable toxicity.

The safety profile of the nivolumab and ipilimumab combination in CheckMate 8HW was consistent with previously reported data for these agents, and no new safety signals were identified. Any-grade TRAEs in the combination and monotherapy arms included pruritus (24% vs 19%, respectively), diarrhea (21% vs 19%), hypothyroidism (16% vs 11%), asthenia (14% vs 12%), fatigue (13% vs 9%), rash (12% vs 10%), adrenal insufficiency (10% vs 5%), increased alanine aminotransferase levels (10% vs 8%), arthralgia (9% vs 6%), and hyperthyroidism (9% vs 6%).

In April 2025, the FDA approved nivolumab/ipilimumab in the aforementioned population.³

References

1. Opdivo® intravenous infusion approved in Taiwan in combination with Yervoy® for the treatment of adult patients with unresectable or metastatic microsatellite instability-high or mismatch repair deficient colorectal cancer. News release. Ono Pharma. January 14, 2026. Accessed January 14, 2026. https://tinyurl.com/5dpwnfkh
2. Lonardi S, Lenz HJ, Elez Fernandez E, et al. Nivolumab plus ipilimumab vs nivolumab monotherapy for microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC): New results from CheckMate 8HW. Presented at: 2025 ESMO Congress; October 17-21, 2025; Berlin, Germany. Abstract LBA29.
3. FDA approves nivolumab with ipilimumab for unresectable or metastatic MSI-H or dMMR colorectal cancer. News release. FDA. April 8, 2025. Accessed January 14, 2026. https://tinyurl.com/3vj77rfh