The U.S. Food and Drug Administration (FDA) has accepted and granted Priority Review to the Biologics License Application (BLA) for patritumab deruxtecan (HER3-DXd) for the treatment of adult patients with locally advanced or metastatic EGFR-mutated non-small cell lung cancer (NSCLC) previously treated with two or more systemic therapies. This decision, announced by Daiichi Sankyo and Merck, aims to address the unmet need for effective treatments in this patient population.
The Prescription Drug User Fee Act (PDUFA) date, which is the FDA action date for their regulatory decision, is June 26, 2024. The Priority Review follows the Breakthrough Therapy Designation granted by the FDA in December 2021.
Clinical Efficacy and Safety
The BLA is based on primary results from the HERTHENA-Lung01 pivotal phase 2 trial, with data presented at the IASLC 2023 World Conference on Lung Cancer and published in the Journal of Clinical Oncology. The trial involved 225 patients with EGFR-mutated locally advanced or metastatic NSCLC who had progressed after treatment with an EGFR TKI and platinum-based chemotherapy.
The HERTHENA-Lung01 trial demonstrated an objective response rate (ORR) of 29.8% (95% CI: 23.9-36.2), including one complete response and 66 partial responses. The median duration of response was 6.4 months (95% CI: 4.9-7.8). The safety profile of patritumab deruxtecan was consistent with previous phase 1 clinical trials in NSCLC. Treatment discontinuation rate due to treatment-emergent adverse events (TEAEs) was 7.1%. Grade 3 or higher TEAEs occurred in 64.9% of patients, with the most common being thrombocytopenia (21%), neutropenia (19%), anemia (14%), and leukopenia (10%). Confirmed treatment-related interstitial lung disease (ILD) was observed in 5.3% of patients, with one grade 5 ILD event.
Mechanism of Action and Potential Impact
Patritumab deruxtecan is a specifically engineered potential first-in-class HER3 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed and commercialized by Daiichi Sankyo and Merck. Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo, stated that the FDA’s prioritization reflects the strength of the HERTHENA-Lung01 data and the need for new options for patients with advanced EGFR-mutated NSCLC. If approved, it could be the first HER3-directed medicine approved in the US and the second DXd antibody drug conjugate from Daiichi Sankyo’s oncology pipeline.
Addressing Unmet Needs in NSCLC
Lung cancer is the second most common cancer and the leading cause of cancer-related deaths worldwide. NSCLC accounts for approximately 85% of all lung cancers, with EGFR mutations occurring in 14% to 38% of all NSCLC tumors worldwide. Marjorie Green, MD, Senior Vice President and Head of Late-Stage Oncology, Global Clinical Development, Merck Research Laboratories, noted that the BLA acceptance is a significant step in potentially bringing a new medicine to previously treated patients with EGFR-mutated NSCLC who often experience recurrence and have few remaining treatment options.
Ongoing Development
Patritumab deruxtecan is also being evaluated in combination with other therapies, including in the HERTHENA-Lung02 phase 3 trial versus platinum-based chemotherapy and a phase 1 trial in combination with osimertinib in EGFR-mutated NSCLC.
