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

Bristol Myers Squibb’s immuno-oncology agents Opdivo and Yervoy missed the mark in a late-stage trial in newly diagnosed bladder cancer, following in the paths of rivals from Roche and Merck that have also struggled in the cancer type.

In the phase 3 CheckMate-901 study, the Opdivo-Yervoy combo failed to trump standard-of-care chemotherapy at extending the lives of patients with untreated unresectable or metastatic urothelial carcinoma whose tumor cells expressed at least 1% of the PD-L1 biomarker, the company said Monday.

“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,” Dana Walker, M.D., vice president and development program lead for genitourinary cancers at BMS, said in a statement.

The data remain blinded, BMS noted. An independent data monitoring committee has suggested the trial remain ongoing to weigh other primary and secondary endpoints. 

Aside from the overall survival primary endpoint, CheckMate-901 is studying whether the combo can benefit patients with unresectable or metastatic urothelial carcinoma who aren’t a good fit for cisplatin-based chemotherapy.

Further, a sub-study of the trial is looking at Opdivo plus chemotherapy versus chemotherapy alone in patients who are eligible for cisplatin-based chemotherapy.

BMS said it will report on those additional legs of the trial when results are available. It didn't give a timeline on when those data are expected.

Bladder cancer is the 10th most common cancer in the world, BMS said, with more than 573,000 cases diagnosed each year. Most urothelial carcinomas are diagnosed early on, but recurrence rates and disease progression are high.

Roughly half of patients who receive surgery for their cancer will have their disease return; moreover, some 20% to 25% of patients with urothelial carcinoma develop metastatic disease, where the prognosis is poor.

Median overall survival for patients with metastatic disease on systemic therapy stands at about 12 to 14 months, BMS said.

The BMS combo isn't alone in facing a trial setback in newly diagnosed bladder cancer.

In 2017, Merck's Keytruda won an accelerated approval for newly diagnosed bladder cancer patients who aren’t suitable for cisplatin-based chemotherapy. The FDA later restricted its approval to patients who aren't eligible for any platinum-containing chemotherapy after an independent data monitoring committee for the med's confirmatory trial flagged that patients who had low PD-L1 expression levels performed even worse on Keytruda than those who were on platinum chemotherapy.

Roche's PD-L1 inhibitor Tecentriq also struggled in a confirmatory trial in front-line bladder cancer. That led the FDA to limit its conditional nod to cisplatin-eligible patients with PD-L1 expression covering at least 5% of tumor-infiltrating immune cells and patients who aren’t suitable for any platinum chemo.


As for BMS' meds, the bladder cancer miss follows several regulatory wins for Opdivo plus a new combo that opened the door to a third immune checkpoint drug class.

First up, Opdivo together with platinum-doublet chemotherapy in March won an FDA nod to treat resectable non-small cell lung cancer before surgery in the neoadjuvant arena.

Notably, the regulator handed down its OK more than four months ahead of its July 13 decision date and just five days after accepting BMS’ application with a priority-review tag.

Meanwhile, the company recently snagged an approval for its third checkpoint inhibitor, the LAG-3 antibody relatlimab, which was cleared in a fixed-dose combination with Opdivo to treat unresectable or metastatic melanoma.

Still, it hasn’t all been smooth sailing for Opdivo-Yervoy in recent months. Back in September, the combo charted two separate flops in front-line patients with recurrent or metastatic head and neck cancer, plus patients with newly diagnosed advanced gastric cancer, gastroesophageal junction cancer or esophageal adenocarcinoma, where the duo failed to significantly extend the lives of patients.

Through the middle of the decade, BMS expects Opdivo and Yervoy, plus its blood thinner Eliquis, to contribute a combined $8 billion to $10 billion in annual growth. That would build on 2020 sales of $8.7 billion for Opdivo-Yervoy and $9.2 billion for Eliquis.

Opvido generated $1.92 billion in the first three months of 2022, climbing 12% over the sum it earned for that period last year. Yervoy, for its part, pulled down $515 million for 2022’s first quarter, growing 13% over the same quarter in 2021.