Multinational phase 2 study of belzutifan for von Hippel-Lindau disease-associated pancreatic lesions

The multinational phase 2 LITESPARK-004 study evaluates the HIF-2α inhibitor belzutifan in patients with von Hippel-Lindau (VHL)-disease. The results of belzutifan treatment for VHLdisease-associated pancreatic lesions (pNETs and serous cystadenoma) have now been published. At baseline, all LITESPARK-004 patients had at least one pancreatic lesion, and 36% had at least one pNET. The objective response rate of the pancreatic lesions to belzutifan was 84% (51/61; 17 complete responses) en the ORR of the pNETs was 91% (20/22; 7 complete responses). During median 37.8 months of follow-up the median duration of response en median progression-free survival were not reached in pancreatic lesions or pNETs. After starting treatment, the median linear growth rate for pNETs was – 4.2 mm per year (range -7.9 to -0.8). Grade 3 treatment-related adverse events were seen in 18% of patients; there were no grade 4 or 5 TRAEs. The authors conclude that belzutifan showed robust actitity for VHL disease-associated pancreatic lesions, with manageable safety.