Academic Journal
Phase I LITESPARK-001 study of belzutifan for advanced solid tumors: Extended 41-month follow-up in the clear cell renal cell carcinoma cohort.
| Title: | Phase I LITESPARK-001 study of belzutifan for advanced solid tumors: Extended 41-month follow-up in the clear cell renal cell carcinoma cohort. |
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| Authors: | Jonasch E; The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: ejonasch@mdanderson.org., Bauer TM; Tennessee Oncology, Nashville, TN, USA., Papadopoulos KP; South Texas Accelerated Research Therapeutics (START), San Antonio, TX, USA., Plimack ER; Fox Chase Cancer Center, Temple Health, Philadelphia, PA, USA., Merchan JR; University of Miami Health System, Miami, FL, USA., McDermott DF; Beth Israel Deaconess Medical Center, Boston, MA, USA., Dror Michaelson M; Massachusetts General Hospital, Boston, MA, USA., Appleman LJ; University of Pittsburgh Medical Center, Pittsburgh, PA, USA., Roy A; Merck & Co., Inc., Rahway, NJ, USA., Perini RF; Merck & Co., Inc., Rahway, NJ, USA., Liu Y; Merck & Co., Inc., Rahway, NJ, USA., Choueiri TK; Dana-Farber Cancer Institute, Boston, MA, USA. Electronic address: toni_choueiri@dfci.harvard.edu. |
| Source: | European journal of cancer (Oxford, England : 1990) [Eur J Cancer] 2024 Jan; Vol. 196, pp. 113434. Date of Electronic Publication: 2023 Nov 15. |
| Publication Type: | Clinical Trial, Phase I; Journal Article |
| Language: | English |
| Journal Info: | Publisher: Elsevier Science Ltd Country of Publication: England NLM ID: 9005373 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0852 (Electronic) Linking ISSN: 09598049 NLM ISO Abbreviation: Eur J Cancer Subsets: MEDLINE |
| Imprint Name(s): | Publication: Oxford : Elsevier Science Ltd Original Publication: Oxford ; New York : Pergamon Press, c1990- |
| MeSH Terms: | Carcinoma, Renal Cell*/drug therapy , Carcinoma, Renal Cell*/pathology , Kidney Neoplasms*/drug therapy , Kidney Neoplasms*/pathology, Basic Helix-Loop-Helix Proteins/therapeutic use ; Humans ; Follow-Up Studies ; Indenes |
| Abstract: | 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. NCT02974738. (Copyright © 2023. Published by Elsevier Ltd.) |
| Competing Interests: | Declaration of Competing Interest E. Jonasch has received research support from MSD, NiKang, Novartis, Arrowhead, Corvus, ProFoundBio, Telix, Aveo; consulting fees from Aveo, Esai, Exelixis, Ipsen, MSD, and NiKang; and honoraria from DAVA; has participated on advisory boards for Novartis; and has a leadership role with NCCN. T. M. Bauer has received research support from MSD, consulting fees from Pfizer, Bayer, Eli Lilly and Company, AstraZeneca, and BluePrint; and honoraria from Pfizer, Bayer, and Eli Lilly.K. P. Papadopoulos has received research support from 3D Medicines, Abbvie, ADC Therapeutics, Amgen, Anheart Therapeutics, Bayer, Daiichi Sankyo, F-Star, Incyte, Jounce, LillyLoxo, MSD, Mersana, Mirati, Pfizer, Regeneron, RevolutionMedicines, Syros Pharma, Tempest Therapeutics, Treadwell Therapeutics, CytomX, AstraZeneca, Kezar, Monte Rosa, and Storm; has received travel support from Jounce; and participated on advisory boards for Basilla, Bicycle, and Turning Point Therapuetics. E. R. Plimack has received research support from MSD, BMS, Seagen, and Genentech; has participated in advisory boards for Astellas, AstraZeneca, Aveo, BMS, Calithera, EMD Serono, Exelixis, IMV, Janssen, MEI, MSD, Pfizer, Regeneron, Seagen, Signatera; and was a member of an external data monitoring committee for AstraZeneca and Infinity Pharma. J. R. Merchan has received research grants from MSD, Sillagen, Seattle Genetics, Genentech, EISAI, Exelixis, Imugene, Rubius Therapeutics, Trishula Therapeutics, Corvus, Peloton Therapeutics, and Vyriad; receives royalties from UpToDate; and has participated on an advisory board for MSD. D. F. McDermott has received research support from BMS, MSD, Genentech, Pfizer, Exelixis, X4 Pharma, and Alkermes, Inc; and has honoraria from BMS, Pfizer, MSD, Eisai Inc., Xilio, Aveo, Genentech, Cullinan, and Exelixis. M. Dror Michaelson has participated on advisory boards for MSD, Eisai, Exelixis, and Janssen. L. J. Appleman has received research support from MSD. A. Roy, R. F. Perini, and Y. Liu are employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA and has stock ownership in Merck & Co., Inc., Rahway, NJ, USA. T. K. Choueiri reports institutional and personal support, paid and unpaid support for research, participating in advisory boards, consultancy, and honoraria from Alkermes, AstraZeneca, Aravive, Aveo, Bayer, Bristol Myers Squibb, Calithera, Circle Pharma, Eisai, EMD Serono, Exelixis, GlaxoSmithKline, Gilead, IQVIA, Infinity, Ipsen, Jansen, Kanaph, Lilly, MSD, Nikang, Nuscan, Novartis, Pfizer, Roche, Sanofi/Aventis, Scholar Rock, Surface Oncology, Takeda, Tempest, UpToDate, and CME events (Peerview, OncLive, MJH, and others), outside the submitted work; institutional patents filed on molecular mutations, immunotherapy response and toxicity, and circulating tumor DNA; equity in Tempest, Pionyr, Osel, Precede Bio, and CureResponse; being part of committees in the National Comprehensive Cancer Network, GU Steering Committee, American Society of Clinical Oncology, European Society for Medical Oncology, Academic and Community Cancer Research United, and KidneyCAN; having mentored several non-US citizens on research projects partly funded by non-US sources; additional independent funding from drug companies or royalties for having received research around the subject matter paid to institution; and is supported in part by the Dana-Farber/Harvard Cancer Center Kidney SPORE (2P50CA101942–16) and Program 5P30CA006516–56, the Kohlberg Chair at Harvard Medical School and the Trust Family, Michael Brigham, and Loker Pinard Funds for Kidney Cancer Research at DFCI. |
| Contributed Indexing: | Keywords: Belzutifan; Hypoxia-inducible factor 2; Kidney cancer; Renal cell carcinoma |
| Molecular Sequence: | ClinicalTrials.gov NCT02974738 |
| Substance Nomenclature: | 0 (Basic Helix-Loop-Helix Proteins) 7K28NB895L (belzutifan) 0 (Indenes) |
| Entry Date(s): | Date Created: 20231126 Date Completed: 20231218 Latest Revision: 20260607 |
| Update Code: | 20260608 |
| DOI: | 10.1016/j.ejca.2023.113434 |
| PMID: | 38008031 |
| Database: | MEDLINE |
| ISSN: | 1879-0852 |
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| DOI: | 10.1016/j.ejca.2023.113434 |