Belzutifan for von Hippel-Lindau Disease: Pancreatic Lesion Population of the Phase 2 LITESPARK-004 Study

Abstract

Purpose: Primary analysis of the ongoing, single-arm, phase 2 LITESPARK-004 study (NCT03401788) showed clinically meaningful antitumor activity in von Hippel-Lindau (VHL) disease-associated renal cell carcinoma (RCC) and other neoplasms with belzutifan treatment. We describe results of belzutifan treatment for VHL disease-associated pancreatic lesions [pancreatic neuroendocrine tumors (pNET) and serous cystadenomas].

Patients and methods: Adults with VHL diagnosis based on germline VHL alteration, ≥1 measurable RCC tumor, no renal tumor >3 cm or other VHL neoplasm requiring immediate surgery, Eastern Cooperative Oncology Group performance status of 0 or 1, and no prior systemic anticancer treatment received belzutifan 120 mg once daily. End points included objective response rate (ORR), duration of response (DOR), progression-free survival (PFS), and linear growth rate (LGR) in all pancreatic lesions and pNETs per RECIST version 1.1 by independent review committee, and safety.

Results: All 61 enrolled patients (100%) had ≥1 pancreatic lesion and 22 (36%) had ≥1 pNET measurable at baseline. Median follow-up was 37.8 months (range, 36.1-46.1). ORR was 84% [51/61; 17 complete responses (CR)] in pancreatic lesions and 91% (20/22; 7 CRs) in pNETs. Median DOR and median PFS were not reached in pancreatic lesions or pNETs. After starting treatment, median LGR for pNETs was -4.2 mm per year (range, -7.9 to -0.8). Eleven patients (18%) had ≥1 grade 3 treatment-related adverse event (AE). No grade 4 or 5 treatment-related AEs occurred.

Conclusions: Belzutifan continued to show robust activity and manageable safety in VHL disease-associated pNETs.

Figure 1.

Best overall response of patients with pancreatic lesions. A, Swimmer plot showing duration of treatment and best response. Each line represents a patient. B, Waterfall plot showing the best percentage change from baseline in total sum of pancreatic lesions.

Figure 2.

Representative images from patients who achieved CRs. A, Scan of a patient with pNET who had a CR at week 202. B, Scan of a patient with non-pNET (serous cystadenoma) who had a CR at week 159.

Figure 3.

Best overall response of patients with pNETs. A, Swimmer plot showing duration of treatment and best response. Each line represents a patient. B, Waterfall plot showing the best percentage of change from baseline in total sum of pNET target lesions.