At a Glance
- South Korea’s MFDS approved Opdivo® + Yervoy® on Feb 23, 2026, for unresectable/metastatic MSI-H/dMMR CRC in adults.
- CheckMate-8HW Phase 3 trial showed superior PFS vs. chemotherapy (first-line) and vs. Opdivo alone (all lines).
- Dual PD-1/CTLA-4 blockade synergistically enhances anti-tumor T-cell response in immunogenic tumors.
- Addresses unmet need in 4% of unresectable CRC cases where chemo shows limited efficacy.
Written By: Nikita Jha, BPharm
Reviewed By: Pharmacally Editorial Team
Ono Pharmaceutical Co., Ltd., through its Korean subsidiary Ono Pharma Korea Co., Ltd., secured additional approval for Opdivo® (nivolumab) Intravenous Infusion combined with Yervoy® (ipilimumab) from South Korea’s Ministry of Food and Drug Safety on February 23.
This approval targets adult patients with unresectable or metastatic microsatellite instability-high (MSI-High) or mismatch repair deficient (dMMR) colorectal cancer (CRC), addressing a critical need in a cancer subtype where conventional treatments often fall short.
Study Basis and Key Findings
The approval is based on the CheckMate-8HW study, (NCT04008030) also known as CA209-8HW or ONO-4538-87. This was a global Phase 3 clinical trial. It randomized around 830 patients with unresectable or metastatic MSI-High/dMMR colorectal cancer (CRC). The treatment tested was Opdivo plus Yervoy, given as 240 mg Opdivo combined with 1 mg/kg Yervoy every 3 weeks for four doses.
After that, patients received 480 mg Opdivo every 4 weeks. This combination outperformed the investigator’s choice of chemotherapy in delaying disease progression. Chemotherapy options included mFOLFOX6 (5-fluorouracil, folinic acid, and oxaliplatin) or FOLFIRI (5-fluorouracil, folinic acid, and irinotecan), sometimes with added bevacizumab or cetuximab.
The improvement was measured as progression-free survival (PFS) by Blinded Independent Central Review (BICR). This benefit was seen specifically in first-line patients. It also showed superior PFS versus Opdivo monotherapy across all treatment lines at interim analysis. The combination’s safety profile aligned with prior data, showing no new signals.
Disease Burden
Colorectal cancer ranks as the third most common cancer globally, with around 1.93 million new cases and 904,000 deaths yearly. In South Korea, it leads as the top cancer, affecting roughly 29,000 people annually and causing 11,000 deaths. About 4% of unresectable CRC cases involve MSI-High/dMMR tumors, which respond poorly to standard chemotherapy, heightening demand for immunotherapies like this PD-1/CTLA-4 inhibitor duo that harness the immune system against these immunogenic tumors.
About Opdivo-Yervoy and Rationale
Opdivo (nivolumab) is a PD‑1 immune checkpoint inhibitor that blocks the interaction between PD‑1 and its ligands, helping T cells recognize and attack cancer cells. Opdivo’s label has progressively expanded from unresectable melanoma to a wide range of solid tumors and hematologic malignancies, such as NSCLC, renal cell carcinoma, gastric and esophageal cancers, mesothelioma, urothelial carcinoma, hepatocellular carcinoma and others.
Yervoy (ipilimumab) is a human monoclonal antibody that targets CTLA‑4, a negative regulator of T‑cell activation. By blocking CTLA‑4 from binding to CD80/CD86, Yervoy enhances T‑cell activation and proliferation and can reduce regulatory T‑cell function, thereby boosting anti‑tumor immune responses.
Opdivo and Yervoy target complementary immune checkpoints PD‑1 and CTLA‑4 that regulate different stages of the T‑cell response. Blocking both pathways can produce a stronger and more durable anti‑tumor immune effect than inhibiting either alone, which is particularly relevant in immunogenic tumors such as MSI‑High/dMMR CRC.
Ono–Bristol Myers Squibb partnership
Ono and Bristol Myers Squibb have a longstanding collaboration in immuno‑oncology centered on Opdivo and Yervoy. In 2011, Ono granted BMS rights to develop and commercialize Opdivo globally, excluding Japan, South Korea and Taiwan, where Ono retained rights. In 2014, the partners expanded their agreement to co‑develop and co‑commercialize multiple immunotherapies, including combination regimens, in Japan, South Korea and Taiwan, enabling coordinated development and rollout of the Opdivo–Yervoy combination across these key Asian markets.
Reference
Opdivo® (nivolumab) Intravenous Infusion Approved in South Korea in Combination with Yervoy® (ipilimumab) for the Treatment of Adult Patients with Unresectable or Metastatic Microsatellite Instability-High or Mismatch Repair Deficient Colorectal Cancer, 24 February 2026, Opdivo® (nivolumab) Intravenous Infusion Approved in South Korea in Combination with Yervoy® (ipilimumab) for the Treatment of Adult Patients with Unresectable or Metastatic Microsatellite Instability-High or Mismatch Repair Deficient Colorectal Cancer | ONO CORPORATE
A Study of Nivolumab, Nivolumab Plus Ipilimumab, or Investigator’s Choice Chemotherapy for the Treatment of Participants With Deficient Mismatch Repair (dMMR)/Microsatellite Instability High (MSI-H) Metastatic Colorectal Cancer (mCRC) (CheckMate 8HW), ClinicalTrials.gov ID NCT04008030, https://clinicaltrials.gov/study/NCT04008030
Thierry André et al, Nivolumab plus Ipilimumab in Microsatellite-Instability–High Metastatic Colorectal Cancer, N Engl J Med 2024;391:2014-2026, https://www.nejm.org/doi/full/10.1056/NEJMoa2402141
André T et al, Nivolumab plus ipilimumab versus nivolumab in microsatellite instability-high metastatic colorectal cancer (CheckMate 8HW): a randomised, open-label, phase 3 trial. Lancet. 2025 Feb 1;405(10476):383-395. Epub 2025 Jan 25. Erratum in: Lancet. 2025 Mar 1;405(10480):700. PMID: 39874977. https://doi.org/10.1016/s0140-6736(24)02848-4
About Writer
Nikita Jha
She is a pharmacy graduate with expertise in clinical research, pharmacovigilance, and medical writing. In her words, she is passionate about translating complex scientific data into clear, accurate healthcare communications that advance drug safety and patient care.