Bristol Myers Squibb snags new liver cancer nod for Opdivo-Yervoy combo

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Tumor response data from a phase 1/2 trial formed the basis for Bristol Myers Squibb's accelerated FDA nod for Opdivo and Yervoy in second-line liver cancer. (Bristol Myers Squibb)

Bristol Myers Squibb’s Opdivo-Yervoy immuno-oncology combo has had some ups and downs lately. But it can now claim a new FDA nod in pretreated liver cancer.

The Opdivo-Yervoy regimen is now FDA-approved to treat hepatocellular carcinoma patients who have previously received Bayer’s standard-of-care Nexavar, Bristol said Wednesday. Because the FDA doled out the indication under an accelerated approval based on tumor response numbers, the company is required to run confirmatory trials.

Bristol was quick to highlight that its pairing is the first dual immunotherapy to win approval in the setting. But if the second-line performance of Opdivo’s PD-1 archrival Keytruda from Merck is any indication, successful tumor suppression in early trials doesn’t necessarily translate into lengthened lives.

Data from the phase 1/2 CheckMate-040 trial formed the basis for Opdivo-Yervoy's new green light. After a minimum follow-up of 28 months, the combo elicited a response in 16 of 49 patients (33%), clearing tumors completely in four of those patients. Responses lasted at last six months in 88% of patients, and 56% felt the tumor-suppressing benefits for at least a year.

The overall response rate was better than the 17% that solo Keytruda posted in the phase 2 Keynote-224 study, which helped the Merck drug land the same second-line liver cancer nod in November 2018. However, just three months after that accelerated approval, Keytruda failed in the confirmatory phase 3 trial dubbed Keynote-240. It didn’t beat placebo at stalling cancer progression or prolonging patients’ lives.

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

Of course BMS—which also boasts an approval for solo Opdivo in the setting—is hoping that that's where the power of two I-O agents can propel it ahead of the competition. In the monotherapy department, Opdivo-Yervoy will also be facing down Bayer's own small-molecule Stivarga. Right now, Stivarga can tout a life extension advantage, which the checkpoint inhibitors still can’t. Clinical data showed patients taking Stivarga lived a median 10.6 months, compared with 7.8 months for those on a placebo.

Because of Stivarga’s proven benefits, several trials are now pairing the targeted drug with immunotherapy in liver cancer. For example, Bayer and Merck are collaborating on a Keytruda-Stivarga combo trial in new liver cancer patients.

Meanwhile, Opdivo-Yervoy has seen its fair share of both wins and misses recently. A few days ago, the pairing showed it could help 56% of previously untreated kidney cancer patients live beyond 42 months, better than the 47% figure Pfizer’s Sutent posted.

But Bristol was recently forced to withdraw an application for the regimen in the all-important first-line non-small cell lung cancer setting in Europe. Regulators there found it impossible to evaluate the data thanks to multiple changes to the design of the key clinical trial, they said. Now, the company’s hopes in that indication are mainly resting on the CheckMate-9LA study, in which Opdivo and Yervoy, when used with two cycles of chemo, significantly extended patients’ lives.

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