Daiichi Sankyo And Merck Withdraw BLA for Patritumab Deruxtecan In EGFR+ NSCLC After Overall Survival Miss

Daiichi Sankyo and Merck have voluntarily withdrawn the Biologics License Application (BLA) for patritumab deruxtecan (HER3-DXd) in the U.S. The BLA sought accelerated approval for the treatment of adult patients with EGFR-mutated advanced non-small cell lung cancer (NSCLC) who had previously undergone two or more systemic therapies. The decision was based on topline results from the HERTHENA-Lung02 Phase 3 trial, in which the overall survival (OS) endpoint did not meet statistical significance.

“EGFR-mutated non-small cell lung cancer has proven to be difficult to treat in the second-line metastatic setting and beyond,” said Ken Takeshita, MD, global head, R&D, Daiichi Sankyo. “While we are disappointed with the overall survival results of HERTHENA-Lung02, we are conducting further biomarker analyses to better identify patients who may benefit from patritumab deruxtecan to guide our continued development in lung cancer. We remain confident in the broad development program of this HER3-directed antibody drug conjugate, which currently includes multiple clinical trials across 15 types of cancer.”

Importantly, the decision is not linked to the Complete Response Letter issued in June 2024, which highlighted issues at a third-party manufacturing site. Patritumab deruxtecan, an investigational HER3-targeting antibody-drug conjugate (ADC), was discovered by Daiichi Sankyo and is being co-developed with Merck. Despite missing the OS endpoint, the progression-free survival (PFS) data was statistically significant, and detailed findings will be presented at the ASCO 2025 Annual Meeting on June 1.

“Lung cancer is one of the leading causes of cancer-related deaths worldwide, and these results are a reminder of how challenging it can be to treat these patients with EGFR-mutated non-small cell lung cancer in the second and later line settings. We would like to thank the patients, their families, and investigators for their participation in this study,” said Eliav Barr, MD, senior vice president, head of global clinical development and chief medical officer, Merck Research Laboratories. 

The Phase 3 HERTHENA-Lung02 trial evaluated patritumab deruxtecan as a monotherapy against standard doublet chemotherapy in patients with advanced EGFR-mutated NSCLC following progression on third-generation EGFR TKI therapy.