Merck’s vaunted PD-1 inhibitor Keytruda took a stumble in a late-stage trial as a treatment of patients with advanced hepatocellular carcinoma (HCC) who were previously treated with systemic therapy.
In the pivotal Phase III KEYNOTE-240 trial, Keytruda plus best supportive care failed to hit endpoints in both overall survival and progression-free survival in comparison to placebo and best supportive care. Merck said in the final analysis of the KEYNOTE-240 data there was some improvement in overall survival, however, that did not meet statistical significance according to trial design. Also, the company said that when it came to progression-free survival, there were favorable results in the Keytruda arm, but again, it did not meet statistical significance.
The key secondary endpoint of objective response rate (ORR) was not formally tested since superiority was not reached for overall survival or progression-free survival. Keytruda continues to show a consistent safety profile.
The failure of KEYNOTE-240 was a blow for Merck in this indication, particularly after Keytruda was approved by the U.S. Food and Drug Administration (FDA) in November 2018 for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with the chemotherapy drug sorafenib.
Roy Baynes, head of global clinical development and chief medical officer of Merck Research Laboratories, said he was disappointed the trial failed to hit its co-primary endpoints. He said the results for overall survival, progression-free survival and objective response rate were “generally consistent” with findings from the trial that secured approval in November.
Merck said the results of this trial have been shared with the FDA and will also be shared at a future medical conference.
Hepatocellular carcinoma is the most common type of liver cancer in adults, which is the sixth most frequently diagnosed cancer worldwide. Hepatocellular carcinoma, which is frequently diagnosed at an advanced stage, has one of the highest mortality rates of solid cancers, with a five-year survival rate of less than 15 percent. Keytruda, which has been one of Merck’s strongest performing drugs over the past few years, is being studied across multiple settings and lines of therapy for HCC through our broad clinical program that includes 10 clinical trials sponsored by Merck or in collaborations. In addition to the KEYNOTE-240 trial and the KEYNOTE-224 trial that was instrumental in the November approval, Keytruda is being investigated in the ongoing Phase III KEYNOTE-394 trial, a randomized, double-blind trial evaluating KEYTRUDA in combination with best supportive care, compared to placebo in combination with best supportive care, in Asian patients with advanced HCC who were previously treated with systemic therapy. In addition, there are several ongoing trials investigating Keytruda in combination with other treatments, including therapies through our collaborations.
Merck announced the failure in the HCC trial shortly after the FDA gave Keytruda its fourth approval as a treatment for skin cancer. On Tuesday, Merck announced the FDA approved Keytruda for the adjuvant treatment of patients with melanoma with the involvement of lymph node(s) following complete resection.