Bristol Myers Squibb's Opdivo-Yervoy Combination Fails to Meet Primary Endpoint in Phase 3 CheckMate-901 Trial for First-Line Bladder Cancer

Compiled by Fan Dongdong

Recently, Bristol-Myers Squibb announced that the efficacy of the immunotherapy drug Opdivo-Yervoy combination in the Phase 3 CheckMate-901 study failed to surpass standard chemotherapy, and could not extend the lives of untreated patients with unresectable or metastatic urothelial carcinoma.

Patients participating in the trial had tumor cells that expressed at least 1% of the PD-L1 biomarker. Bristol-Myers Squibb did not directly admit the trial's failure, arguing that it would be盲目 to judge the efficacy of the Opdivo-Yervoy combination based solely on the trial data. The company stated that the independent data monitoring committee recommended continuing the trial to further evaluate other primary and secondary endpoints.

In addition to the primary endpoint of overall survival, the CheckMate-901 trial is also investigating whether the Opdivo-Yervoy combination can benefit patients with unresectable or metastatic urothelial carcinoma who are ineligible for cisplatin-based chemotherapy. Furthermore, a sub-study within this trial is examining whether patients treated with Opdivo plus chemotherapy versus chemotherapy alone qualify for cisplatin-based chemotherapy. Bristol-Myers Squibb also stated that additional details of the trial will be reported when the trial results become available, but the company did not provide an estimated timeline for when the data will be released.

Bristol-Myers Squibb emphasized that bladder cancer is one of the top 10 most common cancers worldwide, with more than 573,000 new cases diagnosed each year. Although most urothelial cancers are diagnosed in the early stages of the disease, the actual recurrence rate and disease progression among patients remain high. Approximately half of the patients who undergo cancer surgery experience recurrence. Additionally, about 20% to 25% of patients with urothelial carcinoma develop metastatic tumors and have a poor prognosis. The median overall survival for patients with metastatic tumors receiving systemic treatment is only 12 to 14 months.

Notably, the Opdivo-Yervoy combination is not the only therapy to face setbacks in bladder cancer trials. In 2017, Merck's Keytruda received accelerated approval for newly diagnosed bladder cancer patients unsuitable for cisplatin-based chemotherapy. However, the U.S. FDA later restricted its approval to patients ineligible for any platinum-based chemotherapy after an independent data monitoring committee indicated that Keytruda showed less efficacy than platinum chemotherapy in the confirmatory trial among patients with low PD-L1 expression levels.

Besides, Roche's PD-L1 inhibitor Tecentriq is also struggling in the confirmatory trial for first-line bladder cancer. Eventually, the U.S. FDA restricted its approval to patients who are eligible for cisplatin chemotherapy with PD-L1 expression covering at least 5% of tumor-infiltrating immune cells, as well as patients unsuitable for any platinum-based chemotherapy.

Bristol-Myers Squibb had previously estimated that Opdivo, Yervoy, and its blood thinner Eliquis would contribute a combined annual revenue growth of $8 billion to $10 billion by the middle of this century. In the first three months of 2022, Opdivo generated $1.92 billion in revenue, representing a 12% increase from the same period last year. Meanwhile, Yervoy’s performance declined to $515 million in the first quarter of 2022 but still showed a 13% increase compared to the same period in 2021.

Reference Source:

Bristol Myers' Opdivo-Yervoy combo misses mark in newly diagnosed bladder cancer