Ifinatamab Deruxtecan in Patients With Extensive-Stage Small Cell Lung Cancer: Primary Analysis of the Phase II IDeate-Lung01 Trial

作者：Charles M. Rudin, Melissa L. Johnson, Luis Paz‐Ares, Makoto Nishio, Christine L. Hann, Nicolas Girard, Pedro Rocha, Hidetoshi Hayashi, Tetsuya Sakai, Yu Jung Kim, Haichuan Hu, Meng Qian, Jasmeet Singh, J. Godard, Mei Tang, Myung‐Ju Ahn · 发表于：Journal of Clinical Oncology · 年份：2025 · DOI：10.1200/jco-25-02142 · 被引用次数：35 · 研究领域：Lung Cancer Research Studies、Lung Cancer Treatments and Mutations、Multiple Myeloma Research and Treatments

PURPOSE: Treatment options for patients with recurrent or progressive extensive-stage small cell lung cancer (ES-SCLC) are limited. This phase II trial evaluated the efficacy and safety of ifinatamab deruxtecan (I-DXd), a B7 homolog 3-directed antibody-drug conjugate, in patients with previously treated ES-SCLC. METHODS: Patients were randomly assigned to receive I-DXd 8 or 12 mg/kg intravenously once every 3 weeks in part 1 (dose optimization) and received I-DXd 12 mg/kg in part 2 (extension). The primary end point was objective response rate (ORR) by blinded independent central review per RECIST, version 1.1. RESULTS: Overall, 183 patients received I-DXd: 88 in part 1 (8 mg/kg, n = 46; 12 mg/kg, n = 42) and 95 in part 2. The median number of previous lines of treatment was two. In the total 12-mg/kg group from parts 1 and 2 (n = 137), the confirmed ORR was 48.2% (95% CI, 39.6 to 56.9), median duration of response was 5.3 (95% CI, 4.0 to 6.5) months, median time to response was 1.4 (range, 1.0-8.1) months, median progression-free survival was 4.9 (95% CI, 4.2 to 5.5) months, and the 9-month overall survival estimate was 59.1%. Any-grade treatment-related adverse events (TRAEs) occurred in 89.8% of patients (grade ≥3, 36.5%). The most common TRAEs were nausea (43.1%), anemia (34.3%), and neutropenia (34.3%). TRAEs associated with treatment discontinuation and death were reported in 9.5% and 4.4% of patients, respectively. Treatment-related interstitial lung disease (ILD) as d...