A recent press release by Bristol Myers Squibb on Phase III of the CheckMate-901 trial shows that Opdivo (nivolumab) plus Yervoy (ipilimumab) does not offer improvement in overall survival (OS) rates in urothelial carcinoma patients.
Opdivo is an anti-PD-1 drug that inhibits the tumor-killing effects of T-cells; in 2014 it was the first drug of its kind to receive regulatory approval. Yervoy, an anti-CTLA-4 drug that helps support the growth of T-cells, was first approved for use by the FDA in 2011 for patients with melanoma.
Opdivo and Yervoy combination treatments have previously been beneficial in other Phase III clinical trials for non-small cell lung cancer, metastatic melanoma, malignant pleural mesothelioma, advanced renal cell carcinoma, and esophageal squamous cell carcinoma.
The CheckMate-901 trial is a Phase III study that began in 2017 to determine whether Opdivo in combination with Yervoy, or in combination with standard-of-care chemotherapy, is more effective than standard-of-care chemotherapy on its own to successfully treat patients with previously untreated unresectable or metastatic urothelial cancer.
The trial was comprised of 707 patients with untreated unresectable or metastatic urothelial carcinoma. Patients were given 1 mg/kg of Opdivo in combination with 3 mg/kg of Yervoy every three weeks for four cycles. They were then given 480 mg of Opdivo every four weeks for a maximum of two years. The primary endpoint of the study was OS in patients who were ineligible for cisplatin-based chemotherapy, or patients with tumor cell PD-L1 expression ≥1%.
When compared to standard-of-care chemotherapy treatment for untreated unresectable or metastatic urothelial carcinoma, however, Opdivo and Yervoy did not meet the primary endpoint of OS in patients whose tumor cells express PD-L1 ≥1% at final analysis.
“Despite some progress in recent years, metastatic urothelial carcinoma remains a difficult disease to address, with a limited number of treatment options that can extend patients’ lives,” said Dana Walker, M.D., M.S.C.E., vice president, development program lead, genitourinary cancers, Bristol Myers Squibb. “Opdivo plus Yervoy has demonstrated durable, long-term survival improvements in several challenging-to-treat advanced cancers, and we are disappointed that the final analysis of CheckMate-901 did not show this same benefit in urothelial carcinoma patients whose tumor cells express PD-L1 ≥1%.”
Urothelial carcinoma is the fourth most common form of cancer among men, and the tenth most common cancer worldwide. About 550,000 new urothelial carcinoma cases are reported annually. “We remain committed to advancing research in urothelial carcinoma, we look forward to seeing data from other parts of the CheckMate-901 trial, and we thank all of the patients, investigators and site personnel involved,” said Walker.
An independent Data Monitoring Committee has recommended that the CheckMate-901 trial continues so that the other primary and secondary endpoints can still be assessed. Secondary endpoints of the trial include OS in all randomized patients, safety outcomes, and progression-free survival. A sub-study of CheckMate-901 is still in progress that will assess Opdivo and chemotherapy combined against chemotherapy alone in cisplatin-ineligible patients. Opdivo and Yervoy is also currently being tested in patients with cisplatin-ineligible unresectable or metastatic urothelial carcinoma.
Bristol Myers Squibb Provides Update on CheckMate -901 Trial Evaluating Opdivo (nivolumab) Plus Yervoy (ipilimumab) as First-Line Treatment for Patients with Unresectable or Metastatic Urothelial Carcinoma