P2/3, N=154, Not yet recruiting, Merck Sharp & Dohme LLC

Moreover, combining cc-885 with an EPAS1 inhibitor, belzutifan, significantly enhanced the anti-tumor efficacy. Our findings provide a novel and precise therapeutic strategy for VHL-deficient ccRCC by targeting ETS1 degradation and disrupting the ETS1-EPAS1 complex.

The glioblastoma cohort of the phase 1 LITESPARK-001 trial enrolled participants who had received radiotherapy and temozolomide. Although targeting HIF-2α may have a role in advancing treatment options for patients with glioblastoma, single-agent belzutifan did not have antitumor activity in this cohort.

P2/3, N=25, Not yet recruiting, Merck Sharp & Dohme LLC

These features translated into improved biochemical and cellular activity, including inhibition of hypoxia-regulated gene expression. Insights from this campaign ultimately informed the discovery of casdatifan, a clinical-stage HIF-2α inhibitor, underscoring the translational potential of this novel chemotype.

P=N/A, N=100, Not yet recruiting, Chinese University of Hong Kong

P1/2, N=90, Not yet recruiting, Vall D Hebron Institute Of Oncology

In the field of cancer therapeutics, targeting the HIF pathway has emerged as a promising strategy, and the Food and Drug Administration approval in 2021 of Welireg, a novel agent designed to target HIF-2α for the primary treatment of von Hippel-Lindau syndrome, has further validated its favorable prospects in tumor therapy...Currently, a range of therapeutic approaches are available for patients diagnosed with GC, yet the 5-year survival rate remains suboptimal for those with advanced-stage disease. The present review summarizes the regulatory and target roles of HIFs in GC, thus providing references for GC treatment and emphasizing the potential of HIF-targeted therapies to disrupt cancer-associated signaling pathways.

P3, N=758, Recruiting, Merck Sharp & Dohme LLC | Not yet recruiting --> Recruiting

P4, N=20, Xiangya Hospital of Central South University; Xiangya Hospital of Central South University

P2, N=322, Recruiting, Merck Sharp & Dohme LLC | N=170 --> 322

P2, N=50, Active, not recruiting, Peloton Therapeutics, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA) | Trial completion date: Mar 2026 --> Apr 2027 | Trial primary completion date: Mar 2026 --> Apr 2027