Merck’s Keytruda flunks liver cancer confirmatory trial 3 months after accelerated approval

The company said it had shared data from the Phase III study with the FDA. However, per FDA regulations, there is a risk that the accelerated approval for hepatocellular carcinoma could be withdrawn.

One of the indications for Merck & Co.’s cancer immunotherapy drug could be under threat following the announcement Tuesday of negative results from a clinical trial.

The Kenilworth, New Jersey-based company said the Phase III KEYNOTE-240 study of the PD-1 checkpoint inhibitor Keytruda (pembrolizumab) in hepatocellular carcinoma, or HCC, failed to meet its primary endpoint of extending the length of time patients stayed alive, known as overall survival. It likewise did not extend progression-free survival, meaning the amount of time patients live without their disease worsening.

Merck’s shares on the New York Stock Exchange did not fluctuate significantly following the news.

The Food and Drug Administration granted Keytruda the liver cancer indication in November under an accelerated approval based on data from the KEYNOTE-224, a single-arm Phase II study among HCC patients who had been previously treated with Bayer’s drug Nexavar (sorafenib).

Under FDA regulations, a condition for an accelerated approval to be converted into a full approval is that a drug must pass a confirmatory study to further demonstrate its efficacy. Keytruda demonstrated efficacy on the surrogate endpoint of overall response rate – meaning the percentage of patients whose tumors shrank after treatment – with 17 percent of 104 patients responding. However, it failed to confirm efficacy in comparison with placebo plus physician’s choice of best supportive care in the Phase III trial. Because KEYNOTE-240 was negative, it opens the possibility that Keytruda could have its HCC indication withdrawn, though neither Merck nor the FDA has said what will happen.

The company said that results of KEYNOTE-240 will be presented at an upcoming medical meeting and have been shared with the FDA for discussion.

The trial results mark the second time in less than a month that a confirmatory study for a cancer drug has failed. In late January, the FDA and European Medicines Agency said said they had recommended that no new patients be started on Eli Lilly & Co.’s soft-tissue sarcoma drug Lartruvo (olaratumab) following the announcement of negative results from that drug’s Phase III trial. The outcome of the study was announced on Jan. 18 and, as with Keytruda in HCC, means Lartruvo’s soft-tissue sarcoma approval could be withdrawn.

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