Merck’s Keytruda Nabs Another Approval, This One Under FDA’s Real-Time Program

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The U.S. Food and Drug Administration (FDA) granted Merck & Co.’s Keytruda another approval, this one in combination with Alimta (pemetrexed) and platinum chemotherapy for first-line treatment of metastatic non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.

The approval was based on data from the KEYNOTE-189 Phase III clinical trial. The trial evaluated patients regardless of PD-L1 tumor expression, and evaluated Keytruda and pemetrexed and platinum chemotherapy, finding a statistically significant and clinically meaningful improvement in overall survival, cutting the risk of death by half compared to just chemotherapy. It also showed a significant improvement in progression-free survival (PFS) compared to just chemotherapy.

“Keytruda is rapidly becoming a foundation for the treatment of appropriate patients with metastatic non-small cell lung cancer,” said Roger Perlmutter, president of Merck Research Laboratories, in a statement. “Today’s approval of the expanded label for Keytruda based on data from the KEYNOTE-189 trial is an important milestone, and reinforces our steadfast commitment to improving survival outcomes, and providing hope, for more patients with lung cancer.”

Although this was an expected approval, it is a landmark for a different reason. It was approved under the FDA’s new Real-Time Oncology Review (RTOR) Pilot Program. The first to be approved were two Novartis combinations for Kisqali against breast cancer.

The pilot program is part of the FDA’s efforts to streamline approvals. The purpose of the RTOR is “to explore a more efficient review process to ensure that safe and effective treatments are available to patients as early as possible, while maintaining and improving review quality and balancing the review team’s workload through data and analysis standardization, and early iterative engagement with the applicant.”

During the program, the agency chooses several supplemental New Drug Applications (sNDA) and supplemental Biologic License Applications (sBLA) from each clinical division to evaluate “the feasibility and optimize the process for RTOR. Acceptance into the RTOR pilot does not guarantee or influence approvability of the supplement, which is subject to the usual benefit-risk evaluation by FDA scientists.”

There is a variety of criteria that need to be met to in order to be entered in the program, but once in, it allows the FDA to review much of the data earlier before the company has formally submitted a complete application. Those criteria include drugs that are likely to show substantial improvements over currently available therapies, with an emphasis on drugs that had Breakthrough Therapy Designation, fast track or priority review, and straightforward study designs. Of particular import here is that clinical trials that were conducted exclusively outside the U.S., as well as adjuvant, neoadjuvant, and prevention studies are excluded from the program. The endpoints need to be easily interpreted, and exclusions also include supplements with CMC formulation changes and with pharmacology/toxicology data.

“Over the last few years, we’ve seen significant clinical advances and an incredible shift in the way we approach the treatment of people diagnosed with metastatic non-small cell lung cancer,” said Shirish Gadgeel, professor in thoracic oncology at the University of Michigan Rogel Cancer Center, in a statement. “As a practicing physician, I welcome today’s news, as Keytruda in combination with pemetrexed and platinum chemotherapy significantly prolonged overall survival and progression-free survival in the KEYNOTE-189 trial, compared with chemotherapy alone.”