Patritumab deruxtecan was unable to significantly improve overall survival in patients with locally advanced or metastatic non-small cell lung cancer with EGFR mutations.
Merck and Daiichi Sankyo withdrew their regulatory application Thursday for the investigational antibody-drug conjugate patritumab deruxtecan, which the partners were proposing as a treatment for locally advanced or metastatic non-small cell lung cancer.
In explaining the unusual move, the partners said patritumab deruxtecan, also called HER3-DXd, failed to significantly improve overall survival in the Phase III HERTHENA-Lung02 trial, as per a topline readout. Discussions with the FDA also played a role in Merck and Daiichi Sankyo’s decision to pull their application, according to Thursday’s release, though the companies did not reveal what exactly the regulator told them.
They also did not say when or if they plan to refile the application.
Patritumab deruxtecan is an antibody-drug conjugate (ADC) designed to target the HER3 protein, which is highly expressed in many different types of solid tumors. It also carries an exatecan derivative payload, which when released inside a cancer cell can trigger its death.
Merck and Daiichi Sankyo had previously sought a non-small cell lung cancer (NSCLC) approval for patritumab deruxtecan, which the FDA met with a Complete Response Letter in June 2024. At the time, the regulator cited issues with a third-party manufacturer, but did not flag problems with the ADC’s efficacy and safety package. The companies on Thursday emphasized that the voluntary withdrawal of patritumab deruxtecan’s application is unrelated to this prior rejection.
The study used to back patritumab deruxtecan’s application, HERTHENA-Lung02, compared the ADC against doublet chemotherapy and enrolled nearly 280 patients with locally advanced or metastatic NSCLC carrying mutations in the EGFR gene.
In September last year, just a few months after the regulatory rejection, Merck and Daiichi Sankyo announced that patritsumab deruxtecan hit the trial’s primary efficacy endpoint, eliciting a significant improvement in progression-free survival. Overall survival data were immature then, but the companies nevertheless signaled their regulatory intent. 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.”
With Thursday’s news, patritumab deruxtecan follows in the footsteps of datopotamab deruxtecan—likewise a Daiichi Sankyo-partnered ADC, this time with AstraZeneca—for which the regulatory application was withdrawn in November 2024. 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.
The day of the withdrawal, AstraZeneca and Daiichi Sankyo also resubmitted an application targeting a subpopulation of NSCLC patients with EGFR mutations—just as patritumab deruxtecan was attempting to do. The FDA granted this application priority review in January and a decision is expected in the third quarter.
