The U.S. Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) for the Biologics License Application (BLA) seeking accelerated approval of Daiichi Sankyo and Merck?s 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. 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 by Daiichi Sankyo and Merck. The BLA is based on the primary results from the HERTHENA-Lung01 pivotal phase 2 trial that were presented at the IASLC 2023 World Conference on Lung Cancer (#WCLC23) and simultaneously published in theJournal 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 (DoR) was 6.4 months (95% CI: 4.9-7.8). 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.

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 DoR, progression-free survival, disease control rate, and time to response ? all assessed by both BICR and investigator assessment ? as well as investigator-assessed ORR, overall survival, safety and tolerability.

Approximately 226,000 lung cancer cases were diagnosed in the U.S. in 2022.1 Lung cancer is the third most common cancer and the leading cause of cancer-related deaths in the U.S.1 NSCLC accounts for approximately 81% of all lung cancers in the U.S., with 52% having distant spread at diagnosis.2,3 EGFR mutations occur in approximately one in five patients with NSCLC in Western populations. HER3 is a member of the EGFR family of receptor tyrosine kinases.5 It is estimated that about 83% of primary NSCLC tumors and 90% of advanced EGFR-mutated tumors express HER3 after prior EGFR TKI treatment.6,7 HER3 is associated with poor treatment outcomes, including shorter relapse-free survival and significantly reduced survival. There is currently no HER3 directed therapy approved for the treatment of any cancer.