LITESPARK-015 cohort B1 – A phase 2 open-label study of Belzutifan (a HIF-2α inhibitor) monotherapy in patients with von Hippel-Lindau (VHL) disease–associated tumors

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Introduction: Patients (pts) with von Hippel-Lindau (VHL) disease need novel targeted therapies. Hypoxia-inducible factor 2α (HIF-2α) is a key oncogenic driver in VHL disease. Belzutifan (MK-6482), a HIF-2α inhibitor, has shown antitumor activity in pts with advanced renal cell carcinoma (RCC) and pancreatic neuroendocrine tumors (pNETs); more data are needed in VHL disease–associated localized tumors.

Aim(s): Evaluate efficacy and safety of belzutifan in VHL disease–associated localized tumors.

Materials and methods: In this ongoing open-label, multicohort phase 2 study (NCT04924075), cohort B1 is enrolling pts aged ≥18 y with VHL disease diagnosed by local germline testing and/or clinically (per family history and ≥1 VHL-related tumor, ≥2 retinal/CNS hemangioblastomas [HBs], or 1 retinal/CNS HB and ≥1 VHL-related visceral tumor [except renal/epididymal cysts]) and with ≥1 measurable pheochromocytoma/paraganglioma (PPGL), pNET, or RCC (in pts from China/Japan) per RECIST v1.1 by blinded independent central review (BICR). Pts must have ECOG PS ≤1 and no metastatic disease. Pts with PPGL should have adequately controlled blood pressure (≤150/90 mm Hg and no change in antihypertensive therapy within 2 weeks before study treatment). PPGL, pNET, RCC, and other VHL-related tumors should not require immediate surgery. Approximately 92 pts will be enrolled in cohort B1 (30 PPGL, 30 pNET, 32 RCC) and receive belzutifan 120 mg QD until PD or unacceptable toxicity. Tumor imaging is done every 12 weeks. The primary endpoint is tumor-specific objective response rate per RECIST v1.1 by BICR. Secondary endpoints are duration of response, time to response, disease control rate, progression-free survival, overall survival, time to surgery, and safety. Enrolment is ongoing.

Conference:

Presenting Author:

Authors: Walter T, Gong K, Nakamura E, Iliopoulos O, Jimenez C,

Keywords: von Hippel-Lindau disease, belzutifan, MK-6482,