Combination casdatifan plus cabozantinib expansion cohort of phase 1 ARC-20 study in previously treated patients with clear cell renal cell carcinoma.

作者：Toni K. Choueiri, Moshe Chaim Ornstein, Pedro C. Barata, Marc Matrana, Jaime R. Merchan, Craig Gedye, Clara Hwang, Rohit Kumar, Jae‐Lyun Lee, Yinghui Guan, Mohammad Ghasemi, Syed A. Quadri, Christopher Negro, Chen Jianfen, Paul Foster, Manish Monga, Bradley A. McGregor, Sun Young Rha, Alexandra Drakaki · 发表于：Journal of Clinical Oncology · 年份：2025 · DOI：10.1200/jco.2025.43.16_suppl.4506 · 被引用次数：6 · 研究领域：Renal cell carcinoma treatment、Renal and related cancers、Ferroptosis and cancer prognosis

4506 Background: Hypoxia-inducible factor 2-alpha (HIF-2α) is highly dysregulated in clear cell renal cell carcinoma (ccRCC), resulting in increased expression of proteins involved with angiogenesis, proliferation, and cancer cell survival. Casdatifan is an orally bioavailable small-molecule HIF-2α inhibitor. We investigated the safety and efficacy of casdatifan in combination with the anti–vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR-TKI) cabozantinib in previously treated patients with ccRCC in an expansion cohort (casdatifan + cabozantinib) of the phase 1, open-label ARC-20 (NCT05536141) trial. Methods: Patients enrolled in the casdatifan + cabozantinib expansion cohort were previously treated with immunotherapy (IO) alone or with anti-VEGF therapies. Casdatifan 100 mg and cabozantinib 60 mg were given orally once daily. Endpoints included the incidence of treatment-emergent adverse events (AEs) and objective response rate (ORR) by RECIST v1.1. This study is ongoing; data as of January 3, 2025, are reported. Results: Overall, 27 patients with a median (range) follow-up of 2.9 (0.1–6.8) months were enrolled. At data cut off, prior treatment settings included adjuvant only (n = 5/26) and metastatic (1L n = 17/26; 2L n = 4/26). Prior therapies included IO only (n = 15/26) or IO plus VEGFR-TKI (n = 11/26). All grade AEs occurred in 89% of patients with the most common being anemia (n = 16 [59%]) and fatigue (n = 15 [56%]). Most common ( > 10%...