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. The FDA action date for their regulatory decision is June 26, 2024.
Patritumab deruxtecan is a 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 2 trial, 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 (≥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), with one grade 5 ILD event observed.
HERTHENA-Lung01 is a global, multicenter, open-label, two-arm phase 2 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. The primary endpoint 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.
Lung cancer is the second most common cancer and the leading cause of cancer-related deaths worldwide, with NSCLC accounting for approximately 85% of all lung cancers. EGFR mutations occur in 14% to 38% of all NSCLC tumors worldwide. HER3, a member of the EGFR family of receptor tyrosine kinases, is expressed in about 83% of primary NSCLC tumors and 90% of advanced EGFR-mutated tumors after prior EGFR TKI treatment. Currently, there is no HER3 directed therapy approved for the treatment of any cancer.
