FDA Action Alert: Spotlight on Merck’s Keytruda

The FDA calendar has only one PDUFA data scheduled for the next couple of weeks. On Thursday, April 11, the U.S. Food and Drug Administration (FDA) and Merck & Company have a target action date for their supplemental Biologics License Application (sBLA) for Keytruda (pembrolizumab), its anti-PD-1 checkpoint inhibitor, as a monotherapy for the first-line treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) in patients whose tumors expressed PD-L1 without EGFR or ALK genomic tumor aberrations.

The sBLA was built on data from the Phase III KEYNOTE-042 clinical trial. In that trial, Keytruda alone showed a significant improvement in overall survival compared with chemotherapy in this patient population. There was originally an earlier date, but Merck submitted additional data late in 2018, and on December 20, the company indicated the agency found it made up a major amendment and extended the target action date three months to April 11, 2019.

Keytruda is such a successful drug, and Merck has so many ongoing clinical trials, it can be difficult to actually track what’s going on with it. On March 14, 2019, the company announcedthat the European Commission had approved Keytruda in combination with carboplatin and either paclitaxel or nab-paclitaxel, for first-line treatment of adults with metastatic squamous non-small cell lung cancer (NSCLC). That approval was based on data from the Phase III KEYNOTE-407 clinical trial, showing the drug in combination with chemotherapy significantly improved overall survival (OS) in that patient population, reducing the risk of death by 36% compared to chemotherapy alone.

The company also indicated in that announcement that in NSCLC, Keytruda had been approved in Europe for first-line treatment of metastatic nonsquamous NSCLC with pemetrexed and platinum chemotherapy in adults whose tumors have no EGFR or ALK-positive mutations (KEYNOTE-189); first-line treatment of metastatic squamous or nonsquamous NSCLC as monotherapy in adults whose tumors have high PD-L1 expression with no EGFR or ALK-positive tumor mutations (KEYNOTE-024); and locally advanced or metastatic NSCLC in adults whose tumors express PD-L1 and who have received at least one previous chemotherapy treatment (KEYNOTE-010).

And on April 1, Merck announced that Keytruda had been approved by China’s National Medical Products Administration (NMPA) in combination with pemetrexed and platinum chemotherapy for first-line treatment of metastatic nonsquamous NSCLC, with no EGFR or ALK genomic tumor mutations. This was approved conditionally based on overall survival and progression-free survival (PFS) data from Phase III KEYNOTE-189 in patients regardless of PD-L1 tumor expression. Continued approval is based on verification and clinical benefit in Chinese patients in a confirmatory trial. This is the same approval as the first EC approval mentioned above.

“This approval represents a key advance in a country with a high incidence of lung cancer, and where significant progress for the first-line treatment of this devastating disease has been very limited over a number of years,” stated Roy Baynes, Senior Vice President and Head of Global Clinical Development, Chief Medical Officer, Merck Research Laboratories. “This also means that, based on the results of KEYNOTE-189, Keytruda in combination with chemotherapy has now been approved in the U.S., Europe, Japan and China, among other countries, for the first-line treatment of appropriate patients with metastatic nonsquamous non-small cell lung cancer.”

Merck indicates that Keytruda is currently in more than 900 clinical trials in a broad range of cancers and treatment settings.

At the recent American Association for Cancer Research (AACR) meeting, Merck presented results from a post-hoc analysis of patients with liver or brain cancers from the Phase III KEYNOTE-189 trial. The point of the post-hoc analysis was to evaluate outcomes of Keytruda in combination with chemotherapy in liver and brain cancers.

The company also presented pooled data from KEYNOTE-158 and Phase Ib KEYNOTE-028 evaluating Keytruda in patients with previously treated advanced small cell lung cancer (SCLC). Data from these trials supported the company’s first application in SCLC for Keytruda. The sBLA was accepted by the FDA for priority review and has a target action date of June 17, 2019.

https://www.biospace.com/article/fda-action-alert-spotlight-on-merck-s-keytruda/