Patritumab Deruxtecan (HER3-DXd; MK-1022) in Non–Small Cell Lung Cancer After Platinum-Based Chemotherapy and Immunotherapy
Conor Steuer, Hidetoshi Hayashi, Wu‐Chou Su, Makoto Nishio, Melissa L. Johnson, Dong‐Wan Kim, Erminia Massarelli, Enriqueta Felip, Kathryn A. Gold, Haruyasu Murakami, Christina S. Baik, Sang‐We Kim, Egbert F. Smit, Masahiro Fujimura, Pang‐Dian Fan, K Landry Truchon, Xin Su, David Sternberg, Pasi A. Jänne
Abstract
PURPOSE Patritumab deruxtecan (HER3-DXd; MK-1022) is an investigational HER3-directed antibody-drug conjugate composed of a human immunoglobulin G1 monoclonal antibody to HER3 (patritumab) covalently linked via a stable tetrapeptide-based cleavable linker to a topoisomerase I inhibitor payload that has shown durable antitumor activity in previously treated patients with EGFR -mutated advanced non–small cell lung cancer (NSCLC). We extend these observations to patients with advanced NSCLC with other/no identified driver genomic alterations. METHODS Patients with advanced squamous or nonsquamous NSCLC without a common EGFR -activating mutation whose disease had progressed on previous therapies including platinum-based chemotherapy, immune checkpoint inhibitors, and targeted therapy (for patients with known actionable genomic alterations) received HER3-DXd 5.6 mg/kg intravenously once every 3 weeks. The primary end point was confirmed objective response rate (cORR). RESULTS Forty-seven patients were treated with HER3-DXd (median treatment duration, 4.2 [range, 0.7-19.8] months). The cORR was 27.7% (95% CI, 15.6% to 42.6%), and the median duration of response was 8.1 (95% CI, 4.2 to not evaluable) months. The median progression-free survival was 5.5 (95% CI, 4.0 to 11.2) months, and the median overall survival was 15.2 (95% CI, 10.8 to 17.7) months. Similar efficacy was observed in patients with NSCLC harboring identified driver genomic alterations and in those without such genomic features. The rate of study drug discontinuation associated with treatment-emergent adverse events (TEAEs) was 12.8%. Study drug–related grade ≥3 TEAEs occurred in 51.1% of patients and were serious in 12.8% (none were associated with death). Adjudicated treatment-related interstitial lung disease occurred in five patients (10.6%; all grade 1 or 2). CONCLUSION 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.