ArticleNature medicine2021
Inhibition of hypoxia-inducible factor-2α in renal cell carcinoma with belzutifan: a phase 1 trial and biomarker analysis.
Article in Nature medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to 2 registered trials, which are not on this map. Cited by 176 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase 1, Dose-Escalation and Expansion Trial of PT2977, a HIF-2α Inhibitor, in Patients With Advanced Solid Tumors
The BELIEVE-VHL Trial: A Real-world Longitudinal Study on Belzutifan's Effectiveness, Pharmacogenetics, and Pharmacoeconomics in Von Hippel-Lindau (VHL) Syndrome Using the HIF2α Inhibitor Belzutifan
Who cites it
176 citing papers in PubMed, 1 synthesis or guideline pooled it, 280 citations in OpenAlex.
- Efficacy and toxicity of immune checkpoint inhibitors combination therapy for advanced renal cell carcinoma: a systematic review and network meta-analysis.Frontiers in immunology · 2024Pooled it
- Pharmacokinetics, pharmacodynamics and safety of casdatifan, a novel hypoxia-inducible factor-2α inhibitor, in healthy participants.British journal of clinical pharmacology · 2025Trial
- Belzutifan for von Hippel-Lindau disease-associated renal cell carcinoma and other neoplasms (LITESPARK-004): 50 months follow-up from a single-arm, phase 2 study.The Lancet. Oncology · 2025Trial
- Randomized phase II dose comparison LITESPARK-013 study of belzutifan in patients with advanced clear cell renal cell carcinoma.Annals of oncology : official journal of the European Society for Medical Oncology · 2024Trial
- Phase II Study of ONC201 in Neuroendocrine Tumors including Pheochromocytoma-Paraganglioma and Desmoplastic Small Round Cell Tumor.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Trial
- Belzutifan for Renal Cell Carcinoma in von Hippel-Lindau Disease.The New England journal of medicine · 2021Trial
- Identification of novel HIF2α inhibitors: a structure-based virtual screening approach.Journal of enzyme inhibition and medicinal chemistry · 2026Article
- [Belzutifan in the treatment of renal cell carcinoma].Urologie (Heidelberg, Germany) · 2026Article
- Renal Cell Carcinoma in the Geriatric Population: Toward a Frailty-Adapted Therapeutic Paradigm.Journal of clinical medicine · 2026Review
- Article
- Efficacy and Safety of Lenvatinib Plus Everolimus in Metastatic Renal Cell Carcinoma after Immune Checkpoint and VEGFR Tyrosine Kinase Inhibitors Treatment.Cancer research and treatment · 2026Article
- HIF inhibition: Current strategies and clinical challenges.Redox biology · 2026Review
- The clinical landscape of HIF2α inhibitors in oncology.Nature reviews. Clinical oncology · 2026Review
- Rescuing the Function of Missense-Mutated Tumor SuppressorbioRxiv : the preprint server for biology · 2026Article
- Context-dependent variability of HIF heterodimers influences interactions with macromolecular and small molecule partners.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Review
- Glucocorticoids elevate clear cell renal cell carcinoma sensitivity to HIF-2α inhibitors by suppressing H4K12 lactylation.Signal transduction and targeted therapy · 2026Article
- Targeted therapies in pediatric oncology: A start.Molecular therapy. Oncology · 2026Review
- DNA methyltransferase inhibition is a therapeutic vulnerability in VHL-deficient renal cell carcinoma cells.Experimental & molecular medicine · 2026Article
- Belzutifan-induced tumor regression in sporadic hemangioblastoma: a case report and literature review.Journal of neuro-oncology · 2026Review
116 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Commented on by
- Erratum issued
Authors and funding
12 authors at 10 institutions in 1 country.
Funding
Abstract
Hypoxia-inducible factor-2α (HIF-2α) is a transcription factor that frequently accumulates in clear cell renal cell carcinoma (ccRCC), resulting in constitutive activation of genes involved in carcinogenesis. Belzutifan (MK-6482, previously known as PT2977) is a potent, selective small molecule inhibitor of HIF-2α. Maximum tolerated dose, safety, pharmacokinetics, pharmacodynamics and anti-tumor activity of belzutifan were evaluated in this first-in-human phase 1 study (NCT02974738). Patients had advanced solid tumors (dose-escalation cohort) or previously treated advanced ccRCC (dose-expansion cohort). Belzutifan was administered orally using a 3 + 3 dose-escalation design, followed by expansion at the recommended phase 2 dose (RP2D) in patients with ccRCC. In the dose-escalation cohort (n = 43), no dose-limiting toxicities occurred at doses up to 160 mg once daily, and the maximum tolerated dose was not reached; the RP2D was 120 mg once daily. Plasma erythropoietin reductions were observed at all doses; erythropoietin concentrations correlated with plasma concentrations of belzutifan. In patients with ccRCC who received 120 mg once daily (n = 55), the confirmed objective response rate was 25% (all partial responses), and the median progression-free survival was 14.5 months. The most common grade ≥3 adverse events were anemia (27%) and hypoxia (16%). Belzutifan was well tolerated and demonstrated preliminary anti-tumor activity in heavily pre-treated patients, suggesting that HIF-2α inhibition might offer an effective treatment for ccRCC.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.