As reported in the Journal of Clinical Oncology by Steuer et al, findings in a cohort of a phase I trial indicated activity of the HER3-directed antibody-drug conjugate patritumab deruxtecan (HER3-DXd) in patients with advanced squamous or nonsquamous non–small cell lung cancer (NSCLC) without a common EGFR-activating mutation and with disease progression on platinum-based chemotherapy, immune checkpoint inhibitors, and (if relevant) targeted therapy.
Findings in another cohort of the trial showed activity of HER3-DXd in heavily pretreated patients with EGFR-mutated NSCLC.
Study Details
In the international trial, 47 patients with genomic alterations other than an EGFR mutation or no identified driver mutations enrolled between August 2019 and December 2020 were treated with HER3-DXd at 5.6 mg/kg every 3 weeks. The primary outcome measure was confirmed objective response.
Key Findings
Median follow-up was 19.7 months (range = 13.8–29.2 months). Median HER3-DXd treatment duration was 4.2 months (range = 0.7–19.8 months).
Confirmed objective response was observed in 13 patients (27.7%, 95% confidence interval [CI] = 15.6%–42.6%), with complete response in 1. Median duration of response was 8.1 months (95% CI = 4.2 months to not evaluable). An additional 46.8% of patients had stable disease.
Median progression-free survival was 5.5 months (95% CI = 4.0–11.2 months) and median overall survival was 15.2 months (95% CI = 10.8–17.7 months).
Confirmed objective response rates were similar among 21 patients with identified non-EGFR driver mutations vs 26 with no identified driver mutations (28.6% vs 26.9%).
Grade ≥ 3 adverse events occurred in 72.3% of patients (treatment-related in 51.1%), most commonly neutropenia (25.5%), fatigue (17.0%), and thrombocytopenia (14.9%). Serious adverse events occurred in 40.4% of patients. Adverse events led to treatment discontinuation in 12.8% of patients. Treatment-related interstitial lung disease occurred in five patients (10.6%; all grade 1-2). No treatment-related deaths were observed.
The investigators concluded: “The previously reported efficacy and safety of HER3-DXd in heavily pretreated patients with EGFR-mutated NSCLC are also observed in those with other NSCLC subtypes and warrant further clinical evaluation.”
Conor E. Steuer, MD, of Winship Cancer Institute of Emory University, Atlanta, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Daiichi Sankyo Company, Limited, and Merck Sharp & Dohme, LLC, a subsidiary of Merck & Co, Inc. For full disclosures of all study authors, visit the Journal of Clinical Oncology.
