Optimal Ifinatamab Deruxtecan Dose for Patients With Heavily Pretreated Extensive-Stage Small Cell Lung Cancer

According to interim analysis results from the ongoing phase 2 IDeate-Lung01 trial, 12 mg/kg of ifinatamab deruxtecan is preferable to 8 mg/kg among patients with heavily pretreated extensive-stage small cell lung cancer (SCLC). 

These results were first presented by Charles Rudin, MD, PhD, Memorial Sloan Kettering Cancer Center, New York, New York, at the 2024 World Conference on Lung Cancer in San Diego, California. 

In this dose-optimization cohort, 88 patients who received 1 to 3 prior lines of treatment (including platinum-based chemotherapy) were randomized on a 1-to-1 basis to receive either 8 mg/kg (n = 46) or 12 mg/kg (n = 42) of intravenous ifinatamab deruxtecan every 3 weeks. The primary end point was objective response rate (ORR), by blinded independent central review. Key secondary end points included disease control rate and safety. 

At a median follow-up of 5.3 months in the 8 mg/kg arm, the confirmed ORR was 26.1% with 1 complete response, 11 partial responses, 25 patients with stable disease, and 5 patients with progressive disease. At a median follow-up of 5.8 months in the 12 mg/kg arm, the confirmed ORR was 52.4% with 0 complete responses, 22 partial responses, 15 patients with stable disease, and 2 patients with progressive disease. The disease control rates were 80.4% and 90.5%, respectively. 

Grade ≥3 treatment-emergent adverse events were experienced by 39.1% of patients in the 8 mg/kg arm and 45.2% of patients in the 12 mg/kg arm. Grade ≥ 3 drug-related treatment-emergent adverse events were experienced by 13% and 31% of patients, respectively. One death occurred in the 12 mg/kg arm due to a drug-related treatment-emergent adverse event. Patients most frequently experienced fatigue or events that were gastrointestinal or hematologic in nature. Adjudicated interstitial lung disease occurred in 8.7% of patients and 7.1% of patients, respectively. 

As Dr Rudin concluded, “Both [ifinatamab deruxtecan] doses showed clinically meaningful responses in heavily pretreated patients with ES-SCLC [however the] ORR with [ifinatamab deruxtecan] 12 mg/kg was approximately twice that with [ifinatamab deruxtecan] 8 mg/kg.” 

Source: 

Rudin CM, Ahn MJ, Johnson M, et al. Ifinatamab deruxtecan (I-DXd) in extensive-stage small cell lung cancer (ES-SCLC): Interim analysis of Ideate-lung01. Presented at the 2024 World Conference on Lung Cancer. September 7-10, 2024. Abstract OA04.03