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

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 determined by the ILD adjudication committee was reported in 12.4% of patients (grade ≥3, 4.4%). CONCLUSION I-DXd 12 mg/kg once every 3 weeks showed promising efficacy in patients with previously treated ES-SCLC. The observed safety profile was consistent with previous reports, with no new safety signals identified.