Merck, Daiichi Cancel ADC Lung Cancer Bid Over Survival Data

Highlights

• Merck and Daiichi Sankyo have withdrawn their FDA application for patritumab deruxtecan following underwhelming Phase III survival results.
• The HERTHENA-Lung02 trial showed no significant overall survival benefit in EGFR-mutated NSCLC patients.
• The withdrawal is unrelated to a previous FDA rejection tied to manufacturing issues.
• This marks the second ADC withdrawal by Daiichi Sankyo in less than a year, following a similar move for datopotamab deruxtecan.
• The companies have not indicated if or when a new application will be submitted.

Regulatory Withdrawal Linked to Phase III Shortcomings

Merck and Daiichi Sankyo have voluntarily withdrawn their regulatory submission for the investigational antibody-drug conjugate (ADC) patritumab deruxtecan, also known as HER3-DXd. This decision follows the compound’s failure to demonstrate a significant improvement in overall survival in a key Phase III trial. According to the companies, the topline results from the HERTHENA-Lung02 study did not meet expectations, which led to the unusual step of halting the approval process.

“Patritumab deruxtecan was unable to significantly improve overall survival in patients with locally advanced or metastatic non-small cell lung cancer with EGFR mutations.”

While specific details of discussions with the U.S. Food and Drug Administration (FDA) were not disclosed, both companies acknowledged that feedback from the agency influenced their decision to withdraw. No timeline was provided regarding a potential resubmission.

Background on Patritumab Deruxtecan

Patritumab deruxtecan is designed to target the HER3 protein, which is commonly overexpressed in multiple solid tumors. It includes an exatecan derivative as a cytotoxic payload, intended to kill cancer cells upon internalization. The therapeutic had previously encountered regulatory hurdles when the FDA issued a Complete Response Letter (CRL) in June 2024, citing manufacturing issues rather than concerns over efficacy or safety.

“The companies on Thursday emphasized that the voluntary withdrawal of patritumab deruxtecan’s application is unrelated to this prior rejection.”

HERTHENA-Lung02 Study Outcomes

The application for patritumab deruxtecan was supported by data from the HERTHENA-Lung02 trial, which enrolled nearly 280 patients with advanced non-small cell lung cancer (NSCLC) harboring EGFR mutations. The ADC was tested against standard doublet chemotherapy. In earlier disclosures, the drug met the trial's primary endpoint of improving progression-free survival, though overall survival results were still considered immature at the time.

“Ken Takeshita, global head of R&D at Daiichi Sankyo, said at the time that the companies were planning to share the findings with health authorities ‘to discuss next steps.’”

Broader Implications for Daiichi Sankyo’s ADC Portfolio

This development mirrors a similar event involving another Daiichi Sankyo ADC—datopotamab deruxtecan, co-developed with AstraZeneca. That program saw its lung cancer application pulled in November 2024 following unfavorable FDA feedback on the Phase III trial. AstraZeneca and Daiichi Sankyo later resubmitted an application focusing on a narrower subset of NSCLC patients with EGFR mutations, which has since been granted priority review with a decision expected in the third quarter of 2025.

“Speaking to investors last December, Dale Shuster, head of global precision medicine at Daiichi Sankyo, said datopotamab deruxtecan’s Phase III lung cancer trial ‘was not reviewed favorably by the FDA,’ pushing the companies to pull their filing.”