Background: First line CPI-based therapy is the standard of care for advanced RCC. There is a lack of prospective data for cabozantinib after 1L CPI regimens, which is addressed in this study. Methods: CaboPoint (ClinicalTrials.gov identifier: NCT03945773) is an ongoing Phase 2, multicenter, open-label study of cabozantinib in adults with unresectable, locally advanced, or metastatic clear cell RCC who have progressed after 1L CPI-based therapy. Prior treatment with cabozantinib was not permitted. Patients received cabozantinib in two independent cohorts (cohort A [post nivolumab + ipilimumab] and cohort B [post CPI + vascular endothelial growth factor targeted therapy]). Both cohorts received cabozantinib (60 mg/day as starting dose) until study end (18 months after last patient’s enrollment). The primary endpoint was objective response rate (ORR) in Cohort A per RECIST 1.1 evaluated by independent central review; ORR by investigator review has been included as a secondary endpoint for both cohorts. Here we report results from the pre-planned interim analysis of ORR based on investigator assessment in both cohorts that occurred when 80% of patients in cohort A reached at least 3 months of treatment. Results: At the time of this interim analysis, 88 patients had 3 months of follow up (60 in cohort A and 28 in cohort B). Baseline characteristics were similar across cohorts. Patients had an Eastern Cooperative Oncology Group status of 0 (55.0% / 60.7%) and an intermediate or poor International Metastatic RCC Database Consortium risk (46.3% and 13.0% / 40.7% and 11.1%). The most common prior treatment in cohort B was pembrolizumab + axitinib (71.4%), followed by avelumab + axitinib (28.6%). ORR and best overall response at three months of follow-up as assessed by the Investigator are shown in the table. Conclusions: In this interim analysis, cabozantinib demonstrated preliminary efficacy in patients with advanced RCC after progression on CPI-based combination therapy, irrespective of 1L regimen. The CaboPoint trial is ongoing, with the final analysis anticipated in September 2023. Clinical trial information: NCT03945773.

^aInvestigator-assessed ORR was calculated based on the number of patients in each analysis population (cohort A, n = 60; cohort B, n = 28).