Prof. Eric Jonasch (University of Texas MD Anderson Cancer Center) presented the results of a phase 2 trial of MK-6482, the small molecule inhibitor of hypoxia-inducible factor (HIF)-2a in von Hippel-Lindau disease (VHL)-associated renal cell carcinoma (RCC) .
The phase 2 trial enrolled 61 patients with VHL and renal masses. Patients received MK-6482 orally once daily until disease progression, unacceptable toxicity, or investigator's or patient's decision to withdraw. Tumour size was evaluated at screening and every 12 weeks thereafter. No patients had progressive disease on treatment and 58 patients (95.1%) remain on treatment.
The trial met its primary endpoint and showed an objective response rate in RCC tumors per RECIST by an independent review. The confirmed response rate was 27.9%. When also considering the 8 patients with unconfirmed response, the objective response rate was 41.0%. Additionally, 86.9% of patients had a decrease in the size of their target lesions. The median time to response was 5.5 months.
Most treatment-related adverse events (AEs) were grade 1 or 2 in severity. Grade 3 AEs occurred in 9.8% of patients. There were no grade 4 or 5 treatment-related AEs reported. The most common adverse events were anemia (86.9%), fatigue (57.4%), headache (36.1%), dizziness (31.1%), and nausea (24.6%). Anemia was safely managed with long-acting erythropoietin injections.
1. Jonasch E, et al. Phase II study of the oral HIF-2α inhibitor MK-6482 for Von Hippel-Lindau disease-associated renal cell carcinoma. ASCO Virtual Meeting, 29-31 May 2020, Abstract 5003.