Patritumab Deruxtecan BLA Receives CRL from FDA Due to Manufacturing Inspection
核心洞察
The FDA issued a Complete Response Letter (CRL) for patritumab deruxtecan, intended for EGFR (搜索)-mutated non-small cell lung cancer, due to findings at a third-party manufacturing facility.
The CRL did not raise concerns regarding the efficacy or safety data submitted in the Biologics License Application (BLA) for the drug.
Patritumab deruxtecan is a HER3 (搜索)-directed antibody-drug conjugate being developed by Daiichi Sankyo and Merck (搜索) for previously treated NSCLC (搜索).
The FDA has issued a Complete Response Letter (CRL) regarding the Biologics License Application (BLA) for patritumab deruxtecan, a HER3 (搜索)-directed antibody-drug conjugate (ADC) developed by Daiichi Sankyo and Merck (搜索), intended for the treatment of adult patients with locally advanced or metastatic EGFR (搜索)-mutated non-small cell lung cancer (NSCLC (搜索)) who have previously undergone two or more systemic therapies. The CRL was a consequence of findings from an inspection of a third-party manufacturing site.
No Efficacy or Safety Concerns Raised
Importantly, the FDA's Complete Response Letter did not cite any issues related to the efficacy or safety data that were submitted as part of the BLA. This suggests that the concerns are solely focused on manufacturing processes and quality control at the third-party facility.
Ken Takeshita, MD, Global Head of R&D at Daiichi Sankyo, stated, "We will work closely with the FDA and the third-party manufacturer to address the feedback as quickly as possible in order to bring the first HER3 (搜索) directed medicine to patients with previously-treated EGFR (搜索)-mutated non-small cell lung cancer. We remain confident in the ability to develop this medicine to its full potential."
HERTHENA-Lung01 Trial Results
The BLA submission was based on primary results from the HERTHENA-Lung01 pivotal phase 2 trial. In this trial, patritumab deruxtecan demonstrated an objective response rate (ORR) of 29.8% (95% CI: 23.9-36.2) in 225 patients with EGFR (搜索)-mutated locally advanced or metastatic NSCLC (搜索) following disease progression with an EGFR TKI and platinum-based chemotherapy. The median duration of response (DoR) was 6.4 months (95% CI: 4.9-7.8).
The safety profile observed in HERTHENA-Lung01 was consistent with previous phase 1 clinical trials. Treatment discontinuation due to treatment-emergent adverse events (TEAEs) occurred in 7.1% of patients, with grade 3 or higher TEAEs observed in 64.9% of patients. Common grade 3 or higher TEAEs included thrombocytopenia (21%), neutropenia (19%), and anemia (14%).
Unmet Need in EGFR-Mutated NSCLC
Marjorie Green, MD, Senior Vice President and Head of Oncology, Global Clinical Development, Merck (搜索) Research Laboratories, emphasized the need for new treatment options, stating, "Patients with previously treated EGFR (搜索)-mutated non-small cell lung cancer often experience recurrence and have limited treatment options. We are committed to working with Daiichi Sankyo and the FDA to prioritize making patritumab deruxtecan available to these patients in need."
About Patritumab Deruxtecan
Patritumab deruxtecan (HER3 (搜索)-DXd) is an investigational HER3-directed ADC. It is composed of a fully human anti-HER3 IgG1 monoclonal antibody attached to a topoisomerase I inhibitor payload (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. HER3 is a member of the EGFR (搜索) family of receptor tyrosine kinases, and its expression is associated with poor treatment outcomes in NSCLC (搜索).
Ongoing Development Program
Patritumab deruxtecan is currently being evaluated in several clinical trials, including the phase 3 HERTHENA-Lung02 trial comparing it to platinum-based chemotherapy in EGFR (搜索)-mutated NSCLC (搜索), and the phase 2 HERTHENA-PanTumor01 trial in various advanced solid tumors.