Phase I LITESPARK-001 study of belzutifan for advanced solid tumors: Extended 41-month follow-up in the clear cell renal cell carcinoma cohort

Background: Accumulation of the HIF-2α transcription factor is an oncogenic event implicated in the tumorigenesis of clear cell renal cell carcinoma (ccRCC). In the phase I LITESPARK-001 study, the first-in-class HIF-2α inhibitor belzutifan demonstrated antitumor activity and an acceptable safety profile for pretreated patients with advanced ccRCC. Updated data with additional follow-up of > 40 months are presented. Methods: LITESPARK-001 is an ongoing open-label study with a 3 + 3 dose-escalation design followed by an expansion phase. Patients with ccRCC enrolled at 7 sites received belzutifan 120 mg orally once daily until disease progression, unacceptable toxicity, or patient withdrawal. The data cutoff date was July 15, 2021. The primary end point was identifying the maximum tolerated dose and/or the recommended phase II dose. Secondary end points included objective response rate (ORR) and duration of response (DOR) per RECIST v1.1 by investigator assessment and safety. Results: Median follow-up was 41.2 months (range, 38.2–47.7). Patients received a median of 3 (range, 1–9) prior systemic therapies. Of 55 patients, 14 (25 %) achieved an objective response. Median DOR was not reached (range, 3.1 + to 38.0 + months). Adverse events (AEs) attributed to study treatment by investigator assessment were reported in 53 patients (96 %). 22 patients (40 %) had grade 3 treatment-related AEs; the most common were anemia (n = 13; 24 %) and hypoxia (n = 7; 13 %). No grade 4 or 5 treatment-related AEs occurred. Conclusion: After a median follow-up of 41.2 months, belzutifan monotherapy demonstrated durable antitumor activity in patients with advanced ccRCC and acceptable safety. ClinicalTrials.gov.