Fellow Huntsman Cancer Institute, University of Utah, United States
Background: Immune therapy combinations are now standard first-line therapy for pts with mccRCC. We hypothesize that Ave + Cabo will be safe and show clinical activity in mccRCC.
Methods: Phase I 3+3, clinical trial with three dose levels: Cabo 20mg, 40mg and 60mg + Ave (10mg/kg q2weeks) in each arm. Primary endpoints are safety and identification of the recommended phase II dose (RP2D). Key secondary endpoints include objective response rate (ORR) and radiographic progression free survival (PFS). There is a pre-planned dose expansion cohort of 3 patients of the maximum tolerated dose as confirmation of the RP2D.
Results: Twelve patients with newly diagnosed mccRCC were enrolled: Three patients in the 20 and 40 mg cohorts each, and six patients in the 60 mg cohort. IMDC risk were: four (favorable), six (intermediate), and two patients (poor). No dose-limiting toxicities (DLTs) were observed in any cohort (Table 1). Dose reductions were required in 5 of 6 pts in the Cabo 60 mg cohort after the DLT period. . ORR was 50% with one CR and, five PR. The overall clinical benefit (CR+PR+SD) was noted in 92% of the patients. Progress-free survival rate (PFS) was noted in 67.7%, and 33.5% of patients respectively at 6 and 12 months. Additional details will be presented at the meeting.
Conclusions: Cabo/Ave in mccRCC is safe and preliminarily efficacious. The recommended RP2D dose for the combination is Cabo 40mg/day and Ave 10mg/kg q2 weeks due to a high incidence of intolerable grade 2 toxicity for Cabo 60mg/day. To our knowledge, this is the first study to provide the safety data for this novel combination and warrants further validation in larger studies.
