Keytruda, Opdivo suffer setbacks as three-day AdCom wraps ups

The FDA's Oncologic Drugs Advisory Committee (ODAC) has wrapped its three-day review of so-called "dangling" accelerated approvals given to three immunotherapies across six indications, and voted Thursday that in two of those cases, the approvals in question should be rescinded. The AdCom meeting was convened as part of an industry-wide reevaluation of accelerated approvals with confirmatory trials that have not met their primary endpoints.

Keytruda loses gastric cancer vote...

On Thursday, the FDA panel voted 6 to 2 against maintaining the accelerated approval granted to Merck & Co.'s Keytruda (pembrolizumab) for use as a single agent to treat gastric or gastroesophageal junction adenocarcinoma, pending the conduct or completion of additional trials. The indication was for monotherapy use in third-line or later settings in patients whose tumours express PD-L1. Keytruda's accelerated approval was based on objective response data from a mid-stage study, but later results from the Phase III KEYNOTE-061 and KEYNOTE-062 trials did not confirm its benefit.

...but gets backing in HCC

However, Merck's drug did win backing from ODAC members in regards to a particular liver cancer indication. By a vote of 8 to 0, the panel recommended that Keytruda keep its accelerated approval for now as monotherapy in patients with hepatocellular carcinoma (HCC) previously treated with Bayer's Nexavar (sorafenib), even though it missed both the overall survival (OS) and progression-free survival endpoints in the Phase III KEYNOTE-240 trial.

Narrow miss for Opdivo in liver cancer

Meanwhile, ODAC members voted 5 to 4 against maintaining the accelerated approval for Bristol Myers Squibb's Opdivo (nivolumab) as monotherapy in HCC patients previously treated with Nexavar, pending additional trial data. That FDA approval decision was based on tumour response rate and durability of response data in an early study. However, Opdivo failed to significantly prolong OS when used as a first-line treatment for patients in the Phase III CheckMate -459 study against Nexavar.

In response to the vote, Ian Waxman, development lead of gastrointestinal cancers at Bristol Myers Squibb, said "we are disappointed with today's outcome for patients, and we will work closely with the FDA as it completes its review."

Earlier in the week, the ODAC panel voted in favour of Keytruda and Roche's Tecentriq (atezolizumab) keeping their respective accelerated approvals in bladder cancer, while Tecentriq received panel backing for its accelerated approval in triple-negative breast cancer.

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