Bristol Myers Squibb’s (BMS) blockbuster cancer therapies Opdivo (nivolumab) and Yervoy (ipilimumab) failed to meet the primary endpoint as a combination therapy in a Phase III trial in patients with unresectable, locally advanced stage III non-small cell lung cancer (NSCLC).
The 925 participants in the open-label Phase III study (NCT04026412) were administered either Opdivo and concurrent chemoradiotherapy, followed by Opdivo and Yervoy combination therapy (arm A), Opdivo monotherapy (arm B) or concurrent chemoradiotherapy followed by AstraZeneca’s Imfinzi (durvalumab) (arm C).
The combination therapy failed to improve progression-free survival (PFS), the trial’s primary endpoint. BMS did not disclose much detail about the secondary endpoints, such as overall survival (OS), objective response rate (ORR), duration of response (DOR), or the future of the trial.
“Unfortunately, adding immunotherapy concurrently with definitive chemoradiation did not improve PFS outcomes in this setting,” said Joseph Fiore, vice president, global programme lead, thoracic cancers, BMS.
Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor, which has been approved to treat a variety of cancers, including renal cell carcinoma, gastric cancer, B-cell Hodgkin lymphoma and urothelial carcinoma. Yervoy is a cytotoxic T-lymphocyte associated protein 4 (CTLA-4) inhibiting monoclonal antibody. It has been approved as a monotherapy for late-stage melanoma and in combination with Opdivo in multiple oncology indications such as renal cell carcinoma, metastatic colorectal cancer, and malignant mesothelioma.
Cancer immunotherapeutics are high-grossing therapies for BMS, with Opdivo and Yervoy generating $9bn and $2.2bn, respectively, in sales last year, as per the company’s financials.
BMS is looking to expand the approval indications for the checkpoint inhibitor and is evaluating the therapy in multiple indications.
In December 2023, the company announced that Opdivo and Yervoy combination therapy met the co-primary endpoints at a scheduled interim analysis of the Phase III CheckMate-8HW trial. The study evaluated the combination therapy in conjunction with chemotherapy in patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer.
The company has also developed a subcutaneous version of Opdivo, which was found to be non-inferior to the intravenous version in a Phase III CheckMate -67T in patients with advanced or metastatic clear cell renal cell carcinoma (ccRCC).
