When Merck & Co. and Daiichi Sankyo last year received an FDA complete response letter for their HER3-directed antibody-drug conjugate (ADC) patritumab deruxtecan, the companies hoped to address manufacturing concerns flagged by the agency and quickly return to the regulator's desk. But now they're navigating another setback for the drug.
Thursday, the ADC partners disclosed that they have voluntarily withdrawn the Biologics License Application (BLA) for patritumab deruxtecan, also known as HER3-DXd, as a potential treatment for adults with locally advanced or metastatic EGFR-mutated non-small cell lung cancer (NSCLC) who've been previously treated with two or more systemic therapies.
The decision is based in part on topline overall survival (OS) results from the phase 3 HERTHENA-Lung02 trial, the results of which are being presented this coming Sunday at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting. In the study, overall survival (OS) didn't meet statistical significance, the partners said in the Thursday, May 29 release. They also cited discussions with the FDA in their decision to pull the filing.
The HERTHENA-Lung02 abstract went live on the ASCO website on Thursday, ApexOnco notes, showing a progression-free survival (PFS) improvement of just 0.4 months and two deaths due to interstitial lung disease in the HER3-DXd arm.
The HERTHENA-Lung02 confirmatory study is testing HER3-DXd as a monotherapy versus a doublet chemotherapy regimen in patients with EGFR-mutated, advanced NSCLC after disease progression with a third-generation EGFR tyrosine kinase inhibitor. In September, Daiichi and Merck said the trial yielded a statistically significant improvement in PFS.
Previously, the companies had filed for accelerated approval of HER3-DXd based on results from the phase 2 HERTHENA-Lung01 study, which showed that the drug triggered an objective response rate of 29.8% among 225 patients with EGFR-mutated locally advanced or metastatic NSCLC who'd progressed on certain other treatments.
But in the wake of that filing, the FDA rejected the drug last year based on "findings pertaining to an inspection of a third-party manufacturing facility," Daiichi Sankyo said in a June 2024 press release. The CRL did not flag any issues with the data the companies had submitted by that time, Daiichi noted.
HER3-DXd is one of three ADC assets that Merck paid Daiichi $4 billion upfront to co-develop and co-commercialize back in the fall of 2023. When the companies inked the deal, HER3-DXd was seen as the closest therapy involved in the pact to the market.
In Thursday's release, execs for Daiichi and Merck both expressed their interest in continuing to develop the drug.
"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," Ken Takeshita, M.D., Daiichi's global head of R&D, said in a statement.