- MK-6482, a novel hypoxia-inducible factor 2-alpha (HIF-2α) inhibitor demonstrated a favorable safety profile and promising activity in heavily pretreated patients with advanced clear cell renal cell carcinoma (RCC).
Why this matters
- The drug targets HIF-2α, a protein that promotes angiogenesis that fuels kidney tumors. The target was previously believed to be "undruggable".
- In this phase I/II study, 55 patients with previously treated advanced clear cell RCC received MK-6482 orally once daily.
- Primary outcome was safety and secondary outcomes included multiple efficacy measures.
- Funding: MSD.
- 4 patients died from disease-related events and none from a treatment-related event.
- 65% of patients had grade 3-5 adverse events and 5 patients had a toxicity-related dose reduction.
- Partial responses were observed in 2 out of 5 favorable-risk patients, 10 out of 40 intermediate-risk patients and 1 out of 10 poor-risk patients.
- The overall response rate was 24% and the clinical benefit rate (stable disease plus responsive disease) was 80%.
- The median duration of response had not been achieved; 81% of patients had an estimated response of >6 months, and 29% continued treatment beyond 12 months.
- Median progression-free survival was 11 months.
- Small sample size.
Dr Monty Pal, MD, RCC specialist at the City of Hope Comprehensive Cancer Center, Duarte, CA, said: "The response rate is incredible, given the previous lines of therapy."