|The following article features coverage from the American Society of Clinical Oncology 2020 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.|
Treatment of von Hippel-Lindau (VHL) disease–associated clear cell renal cell carcinoma (ccRCC) with a HIF-2α inhibitor demonstrated antitumor activity and was tolerable, according to interim results from a phase 2 study. These findings were presented at the ASCO20 Virtual Scientific Program.
Germline mutations in VHL results in constitutive activation of the HIF-2α transcription factor, and is associated with an increased risk for several cancer types. “Multifocal bilateral renal cell carcinomas occur in 25% to 60% of persons, and is a key cause of morbidity and mortality,” explained Eric Jonasch, MD, of the University of Texas MD Anderson Cancer Center in Houston, and lead author and presenter.
MK-6482 is a small molecule HIF-2α inhibitor that showed promising efficacy and safety in a previous phase 1/2 trial.
In this open-label, phase 2 trial, 61 patients with confirmed pathologic germline VHL alterations and localized or nonmetastatic ccRCC were treated with MK-6482. The primary endpoint was objective response rate (ORR) of the VHL-associated ccRCC tumor. Secondary endpoints included ORR in nonrenal lesions, duration of response (DOR), time to response (TTR), progression-free survival (PFS), and safety.
At baseline, the median age of patients was 41 and 52.5% were male. Nonrenal tumors were present; the most common were central nervous system hemangioblastomas (80.3%), pancreatic tumors (50.8%), and retinal lesions (27.9%). Prior surgery had been performed in 90.2% of patients, including 52.5% who had undergone partial nephrectomy.
The confirmed ORR was 27.9% (95% CI, 17.1%-40.8%) and an additional 13.1% were not yet confirmed; all were PRs. Most patients (86.9%) experienced a reduction in ccRCC tumor size, with extra-renal responses also observed. The DOR was not yet reached and the median TTR was 23.7 weeks.
The 1-year PFS was 98.3%. Median PFS was not yet reached.
Most treatment-related adverse events (TRAEs) were grade 1 or 2, with 9.8% of patients experiencing grade 3 TRAEs. The most common grade 3 TRAEs were fatigue and anemia. No grade 4 or 5 TRAEs were reported. No patients discontinued treatment due to a TRAE.
“In conclusion, promising clinical activity was observed with MK-6482 in treatment-naive patients with VHL-associated renal cell carcinoma,” Dr Jonasch said. “Clinical activity was also observed in nonrenal cell carcinomas, including hemangioblastomas.”
Disclosure: Research funding for this study was provided by Merck Sharp & Dohme Corp. For a complete list of author disclosures, please refer to the reference.
Read more of Cancer Therapy Advisor‘s coverage of the ASCO 2021 meeting by visiting the conference page.
Jonasch E, Donskov F, Iliopoulos O, et al. Phase II study of the oral HIF-2α inhibitor MK-6482 for Von Hippel-Lindau disease–associated renal cell carcinoma. Presented at: ASCO20 Virtual Scientific Program. J Clin Oncol. 2020;38(suppl):abstr 5003.