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.
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.
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.
After a median follow-up of 41.2 months, belzutifan monotherapy demonstrated durable antitumor activity in patients with advanced ccRCC and acceptable safety.
gov. NCT02974738.
European journal of cancer (Oxford, England : 1990). 2023 Nov 15 [Epub ahead of print]
Eric Jonasch, Todd M Bauer, Kyriakos P Papadopoulos, Elizabeth R Plimack, Jaime R Merchan, David F McDermott, M Dror Michaelson, Leonard J Appleman, Ananya Roy, Rodolfo F Perini, Yanfang Liu, Toni K Choueiri
The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: ., Tennessee Oncology, Nashville, TN, USA., South Texas Accelerated Research Therapeutics (START), San Antonio, TX, USA., Fox Chase Cancer Center, Temple Health, Philadelphia, PA, USA., University of Miami Health System, Miami, FL, USA., Beth Israel Deaconess Medical Center, Boston, MA, USA., Massachusetts General Hospital, Boston, MA, USA., University of Pittsburgh Medical Center, Pittsburgh, PA, USA., Merck & Co., Inc., Rahway, NJ, USA., Dana-Farber Cancer Institute, Boston, MA, USA. Electronic address: .