Opdivo/Yervoy Combo Fails to Meet Endpoints in Head and Neck Cancer
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Bristol Myers Squibb, the global biopharmaceutical firm, has shared new details on its ongoing Phase III research on a potential first-line treatment for people who have been diagnosed with recurrent or metastatic squamous cell carcinoma of the head and neck.
The randomized, multi-center study called CheckMate -651 evaluates Opdivo 3 mg/kg every two weeks in combination with Yervoy 1mg/kg every six weeks. It compares these with the extreme regimen of cetuximab, cisplatin/carboplatin, and fluorouracil to treat patients with recurrent or metastatic SCCHN. The dual primary endpoints of the trial are overall survival in the all-randomized population and in patients whose tumors expressed PD-L1 with a combined positive score of ≥ 20.
Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor designed to harness the body's immune system to restore the anti-tumor immune response. Yervoy is a recombinant, human monoclonal antibody that binds to cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and blocks the interaction of CTLA-4 with its ligands CD80/CD86. In 2011, the US FDA approved the use of Yervoy on patients with unresectable or metastatic melanoma, and it is also approved in more than 50 countries.
The results show that although Opdivo plus Yervoy exhibited a clear, positive trend towards overall survival in such patients, the study was not able to meet its primary endpoints. In addition, the safety profile of the said combination remained consistent with the result of previous studies involving solid tumors.
The secondary endpoints include overall survival in patients with PD-L1-expressing tumors at different cut-off values, objective response rate, duration of response, and progression-free survival in all participants and those with PD-L1.
In the past, specifically the CheckMate -141 trial, Opdivo monotherapy showed a survival benefit in adults with recurrent or metastatic SCCHN after platinum-based therapy. This is why the U.S. Food and Drug Administration and the European Medicines Agency gave Opdivo the green light for this purpose in 2016.
To provide further context, significant improvements to overall survival were observed with the Opdivo plus Yervoy combination in six Phase 3 clinical trials on five different tumors. These are metastatic melanoma, non-small cell lung cancer, malignant pleural mesothelioma, advanced renal cell carcinoma, and esophageal squamous cell carcinoma.
Despite the recent results on CheckMate -651, Bristol Myers Squibb researchers remain optimistic.
"In the CheckMate -651 trial, Opdivo plus Yervoy showed a positive overall survival trend relative to EXTREME in patients with squamous cell carcinoma of the head and neck whose tumors express PD-L1, despite the control arm performing better than expected based on historical data," said Abderrahim Oukessou, M.D., vice president for thoracic cancers and development lead at Bristol Myers Squibb.
"We are disappointed that these results did not reach statistical significance, and we remain committed to advancing research and supporting patients with this difficult-to-treat cancer," he continued.
Head and neck cancer, the sixth most common cancer globally, usually starts in the squamous cells that line the moist mucosal surfaces in these areas. It logs around 930,000 new cases diagnosed and over 467,000 related deaths every year. Risk factors for SCCHN can be viral (associated with the human papillomavirus) or behavioral, including alcohol consumption and smoking.