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Third-Party Manufacturing Issues Prompt FDA Complete Response Letter for Merck and Daiichi Sankyo's Patritumab Deruxtecan | iPharmaCenter

No efficacy or safety concerns identified in the submitted application data

Merck and Daiichi Sankyo have received a Complete Response Letter (CRL) from the U.S. Food and Drug Administration (FDA) regarding their Biologics License Application (BLA) for patritumab deruxtecan (HER3-DXd). The application sought accelerated approval for the treatment of adult patients with locally advanced or metastatic EGFR-mutated non-small cell lung cancer (NSCLC) who have been previously treated with two or more systemic therapies.

The CRL was issued due to findings from an inspection at a third-party manufacturing facility. Importantly, the letter did not highlight any issues with the efficacy or safety data included in the application.

Patritumab deruxtecan is a novel HER3 directed DXd antibody-drug conjugate (ADC) developed by Daiichi Sankyo and co-developed with Merck.

The BLA submission was supported by primary results from the HERTHENA-Lung01 pivotal phase 2 trial, presented at the IASLC 2023 World Conference on Lung Cancer and published in the Journal of Clinical Oncology.

In the HERTHENA-Lung01 trial, patritumab deruxtecan was evaluated in 225 patients with EGFR-mutated locally advanced or metastatic NSCLC who had disease progression following an EGFR TKI and platinum-based chemotherapy. The trial demonstrated an objective response rate (ORR) of 29.8%, including one complete response and 66 partial responses. The median duration of response (DoR) was 6.4 months.

The safety profile observed in HERTHENA-Lung01 was consistent with previous phase 1 trials in NSCLC, showing 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, with the most common (≥5%) being thrombocytopenia (21%), neutropenia (19%), anemia (14%), leukopenia (10%), fatigue (6%), hypokalemia (5%), and asthenia (5%). Additionally, 12 patients (5.3%) experienced confirmed treatment-related interstitial lung disease (ILD), with one grade 5 ILD event reported.

About HERTHENA-Lung01

HERTHENA-Lung01 is a global, multicenter, open-label, two-arm phase 2 trial designed to evaluate the safety and efficacy of patritumab deruxtecan in patients with EGFR-mutated locally advanced or metastatic NSCLC following disease progression on an EGFR TKI and platinum-based chemotherapy. Patients were randomized 1:1 to receive either 5.6 mg/kg (n=225) or an uptitration regimen (n=50). The uptitration arm was discontinued after a risk-benefit analysis from the phase 1 trial recommended the 5.6 mg/kg dose.

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.


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