Keytruda’s use in previously treated liver cancer was one of several accelerated approvals the FDA recently targeted for failure to confirm clinical benefit. But a new trial win looks like a lifeline for the Merck immunotherapy.
Keytruda helped liver cancer patients previously treated with Bayer’s Nexavar live significantly longer than placebo did, Merck said Monday. The PD-1 inhibitor, used with best supportive care, also worked better at slowing tumor progression or shrinking tumors.
The new win came from the Keynote-394 study in Asian patients. It’s a much-needed win for Keytruda after the drug failed in a similar, global phase 3 trial, which put its conditional nod in post-Nexavar liver cancer in jeopardy.
Merck’s Keytruda originally scored its second-line go-ahead in late 2018 based on tumor response data from a smaller Keynote-224 study. Under the FDA’s accelerated approval requirements, Merck conducted Keynote-240 in post-Nexavar patients as the confirmatory trial.
Results from that confirmatory phase 3 trial showed Keytruda reduced the risk of death by 22% over placebo, narrowly missing the statistical significance bar. Patients who got Keytruda lived a median 13.9 months, versus 10.6 months for the placebo group.
After that result, the FDA put Keytruda’s second-line liver cancer indication under the microscope during a recent advisory committee meeting. At the conference in April, external experts voted unanimously to keep the use in place, arguing that the FDA could wait for readout from Keynote-394 to make a decision. Now with a positive outcome, the trial could help turn Keytruda’s conditional nod into a full approval.
At the same meeting, Bristol Myers Squibb’s rival PD-1 Opdivo failed to win backing for its own post-Nexavar treatment partly because it lacked an alternative confirmatory trial that could report data soon. The New York pharma in July unveiled that it was voluntarily pulling that use off Opdivo’s U.S. label.
The regulatory scrutiny Merck and BMS felt for their second-line liver cancer indications came in part thanks to a new green light for Roche’s Tecentriq in newly diagnosed patients. Last May, Tecentriq’s cocktail with fellow Roche med Avastin became the first PD-1/L1 regimen to reach previously untreated liver cancer. With that approval in place, regulators felt more comfortable taking a closer look at the BMS and Merck drugs.
For its part, as the undisputed leader across the PD-1/L1 class, Keytruda is also gunning for the front-line liver cancer setting. But after Roche’s historic go-ahead—which came off gold-standard life extension data—the FDA last July rejected Merck and partner Eisai’s application for the Keytruda-Lenvima combo because the pair only had early-stage tumor response data from a single-arm study.
Keytruda’s second-line liver cancer use fell under FDA’s scrutiny amid an FDA campaign targeting past accelerated approvals that have failed to meet confirmatory trial requirements. The agency is convening another advisory committee meeting this December to discuss two more problematic indications by Secura Bio’s Farydak and Aurobindo Pharma’s Marqibo.