Phase II study of the oral HIF-2α inhibitor MK-6482 for Von Hippel-Lindau disease-associated ccRCC

Abstract No : Abstract #LBA26

Indication : Renal cell carcinoma

Intervention : MK 6482 + cabozantinib

Company : Merck & Co.

Technology : PD-1/MultiTKI Inhibitor


As of June 1, 2020, 56 of 61 (92%) enrolled pts remain on treatment with a minimum of 60 wks follow-up. All pts had ccRCC, 100% had pancreatic lesions, 70% had CNS hemangioblastomas, and 26% had retinal lesions evaluable by IRC. For ccRCC, ORR was 36% (95% CI, 24-49%) and an additional 7 (11%) unconfirmed responses (documented at single time point and pending confirmation at data cutoff) were reported by IRC; all responses were PRs. DOR in confirmed responses was not reached (NR; range, 12-62 wks). The PFS rate at 52 wks was 98% (95% CI, 89-100%). For non-RCC tumors, per IRC, the ORR was 64% (4 CRs) in pancreatic lesions and 30% (5 CRs) in CNS hemangioblastomas; median DOR was NR (range, 11-71 wks) in pts with pancreatic lesions and NR (range, 12-72 wks) in pts with central nervous system hemangioblastomas. Of 16 pts with evaluable retinal lesions at baseline, 11 (69%) showed improvement per IRC. Treatment-related AEs were reported by 98% of pts; 13% had grade 3 TRAEs. There were no grade 4-5 TRAEs. Five pts discontinued treatment (patient decision [n=3], treatment-related adverse event [n=1; grade 1 dizziness], and death [n=1; acute fentanyl toxicity]).


MK-6482 continued to demonstrate promising antitumor activity against VHL-associated RCC and non-RCC tumors and was well tolerated