ASCO-GU 2020 — Clear cell RCC: novel drug holds promise for advanced cases


  • Pavankumar Kamat
  • Univadis
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Takeaway

  • 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".

Study design

  • 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.

Key results

  • 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.

Limitations

  • Small sample size.

Expert commentary

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."