Patritumab Deruxtecan (HER3-DXd; MK-1022) in Non–Small Cell Lung Cancer After Platinum-Based Chemotherapy and Immunotherapy

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.