Patritumab deruxtecan granted priority review in the U.S. for certain patients with previously treated locally advanced or metastatic EGFR-mutated non-small cell lung cancer.- Daiichi Sankyo + Merck Inc.
Daiichi Sankyo and Merck Inc., known as MSD outside of the United States and Canada, announced today that the 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.
The Prescription Drug User Fee Act (PDUFA) date, the FDA action date for their regulatory decision, is June 26, 2024 . The Priority Review follows receipt of Breakthrough Therapy Designation granted by the FDA in December 2021.
The FDA grants Priority Review to applications for medicines that, if approved, would offer significant improvements over available options by demonstrating safety or efficacy improvements, preventing serious conditions or enhancing patient compliance. The BLA is being reviewed under the Real-Time Oncology Review (RTOR) program, an initiative of the FDA which is designed to bring safe and effective cancer treatments to patients as early as possible. RTOR allows the FDA to review components of an application before submission of the complete application.
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.
The BLA is based on the primary results from the HERTHENA-Lung01 pivotal phase II trial and data results presented at the IASLC 2023 World Conference on Lung Cancer (#WCLC23), which were simultaneously published in the Journal of Clinical Oncology.
In HERTHENA-Lung01, patritumab deruxtecan was studied in 225 patients with EGFR-mutated locally advanced or metastatic NSCLC following disease progression with an EGFR TKI and platinum-based chemotherapy, which 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 observed in HERTHENA-Lung01 was consistent with previous phase 1 clinical trials in NSCLC with a treatment discontinuation rate of 7.1% due to treatment-emergent adverse events (TEAEs). Grade 3 or higher TEAEs occurred in 64.9% of patients. The most common (greater than 5 %) grade 3 or higher TEAEs were thrombocytopenia (21%), neutropenia (19%), anemia (14%), leukopenia (10%), fatigue (6%), hypokalemia (5%) and asthenia (5%). Twelve patients (5.3%) had confirmed treatment-related interstitial lung disease (ILD) as determined by an independent adjudication committee. One grade 5 ILD event was observed.
About HERTHENA-Lung01: HERTHENA-Lung01 is a global, multicenter, open-label, two-arm phase II trial evaluating the safety and efficacy of patritumab deruxtecan in patients with EGFR-mutated locally advanced or metastatic NSCLC following disease progression with an EGFR TKI and platinum-based chemotherapy. Patients were randomized 1:1 to receive 5.6 mg/kg (n=225) or an uptitration regimen (n=50). The uptitration arm was discontinued as the dose of 5.6 mg/kg of patritumab deruxtecan was selected following a risk-benefit analysis conducted from the phase 1 trial assessing the doses in a similar patient population. The primary endpoint of HERTHENA-Lung01 was ORR as assessed by blinded independent central review (BICR). Secondary endpoints included duration of response, progression-free survival (PFS), disease control rate, and time to response – all assessed by both BICR and investigator assessment – as well as investigator-assessed ORR, overall survival (OS), safety and tolerability. HERTHENA-Lung01 enrolled patients in Asia, Europe, North America and Oceania. For more information about the trial, visit ClinicalTrials.gov.
Daiichi Sankyo and Merck entered into a global collaboration in October 2023 to jointly develop and commercialize patritumab deruxtecan (HER3-DXd) , ifinatamab deruxtecan (I-DXd) and raludotatug deruxtecan (R-DXd), except in Japan where Daiichi Sankyo will maintain exclusive rights. Daiichi Sankyo will be solely responsible for manufacturing and supply.
See- "HERTHENA-Lung01, a Phase II Trial of Patritumab Deruxtecan (HER3-DXd) in Epidermal Growth Factor Receptor–Mutated Non–Small-Cell Lung Cancer After Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy and Platinum-Based Chemotherapy". Helena A. Yu , MD; Yasushi Goto , MD; Hidetoshi Hayashi , MD, PhD3; Enriqueta Felip , MD, PhD; James Chih-Hsin Yang , MD, PhD; et al.,. DOI: 10.1200/JCO.23.01476 Journal of Clinical Onclogy 41, No. 35 (December 10, 2023) 5363-5375. Published online September 10, 2023.
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