Bristol-Myers Squibb's Opdivo misses its shot at earlier use in liver cancer

Bristol-Myers Squibb’s Opdivo already boasts an FDA approval in liver cancer patients who have been treated with Bayer’s Nexavar. But its quest to jump into the front line just hit a snag.

The BMS PD-1 drug failed to beat Nexavar at extending patients’ lives in a phase 3 study, the company acknowledged Monday. The Bayer drug has long been as the standard of care for patients with newly diagnosed hepatocellular carcinoma (HCC), competition-free in that indication until Eisai and Merck & Co.’s Lenvima just recently joined it.

While Bristol’s survival data didn’t meet the statistical significance bar in the trial, dubbed CheckMate-459, BMS said there was “a clear trend” toward improvement with Opdivo.

RELATED: Merck's Keytruda hits the skids in pivotal trial, putting its liver cancer nod at risk

With an accelerated second-line nod the FDA granted in 2017, “Bristol seemed to be well positioned from a timing perspective,” in the liver cancer market, which numbers about 11,000 patients in the U.S., Credit Suisse analyst Vamil Divan said in a Monday note to clients. Opdivo has been grabbing share in that indication, and Merck’s rival immunotherapy Ketyruda, which bears its own green light in the setting, just failed to confirm its own approval by showing it couldn't fend off tumor progression or prolong patients’ lives.

BMS hasn’t revealed its own overall survival data for second-line use of Opdivo. But the tumor response rate it induced in the CheckMate-040 trial, 14.3%, isn’t that much different from the 17% Keytruda posted in its phase 2 Keynote-224 study.

Divan also cautioned that the trial failure at hand could leave room for Merck, Roche or AstraZeneca, “with the various combination trials they are currently running,” to step in as the leader of the liver cancer pack. And aside from Keytruda, Opdivo is also battling targeted therapies such as Bayer’s Stivarga and Eli Lilly’s Cyramza in the second line.

RELATED: Roche's Tecentriq extends its hot streak with liver cancer combo breakthrough

Meanwhile, Roche’s Tecentriq-Avastin combo might have a chance at the first-line HCC market. In a phase 1b study, the Roche pair showed it could provoke a response in 65% of patients at a median 10.3 months of follow-up. Thanks to that data, presented at last year’s American Society of Clinical Oncology annual meeting, the FDA granted the regimen a breakthrough therapy designation.

BMS’ current trial failure marks another setback in the company's attempts to add new indications for Opdivo. A combination of Opdivo and radiation therapy recently flopped in a phase 3 brain tumor trial.

But the U.S. pharma isn’t giving up in HCC. It plans to evaluate insights garnered from the trial, Ian Waxman, BMS’ development lead in gastrointestinal cancers, said in a statement, stressing that the company remains confident in Opdivo’s role in this tumor type.

Also in the second line, the company is testing the anti-PD-1 in tandem with CTLA-4 inhibitor Yervoy. The combo provoked an objective response rate of 31% with a median duration of 17.5 months, according to data also from the CheckMate-040 trial, presented at this year’s ASCO annual meeting. But the combo has its own history of trial failures. Recently, it couldn't prove better than Opdivo alone in previously treated head and neck cancer.