CaboPoint: A Phase 2 Study of Second-line Cabozantinib After Checkpoint Inhibitor-based Combination Therapy in Patients with Metastatic Renal Cell Carcinoma.

[BACKGROUND AND OBJECTIVE] Data are limited regarding pure second-line cabozantinib use after standard first-line checkpoint inhibitor (CPI)-based combination therapy for advanced renal cell carcinoma (aRCC). We report the final results from the prospective CaboPoint study.

[METHODS] The phase 2, multicentre, open-label CaboPoint study (NCT03945773) evaluated the efficacy and safety of second-line cabozantinib in adults with aRCC, after prior ipilimumab plus nivolumab (IpiNivo; cohort A) or CPI therapy plus vascular endothelial growth factor-targeted therapy (cohort B). The primary endpoint was objective response rate (ORR) as per Response Evaluation Criteria in Solid Tumors 1.1, evaluated by independent central review (ICR) in cohort A. The secondary endpoints included ORR by ICR in cohort B, ORR by investigator review, progression-free survival, overall survival, and safety.

[KEY FINDINGS AND LIMITATIONS] Overall, 127 patients were enrolled from 2020 to 2023 across 40 institutions. The median follow-up was 19.3 mo. ORRs (95% confidence interval [CI]) by ICR were 40.5% (29.6-52.1%) in cohort A (statistically significant and clinically meaningful) and 27.5% (14.6-43.9%) in cohort B; according to the investigator review, ORRs were 49.4% (38.4-60.5%) in cohort A and 33.3% (19.6-49.5%) in cohort B. The median (95% CI) progression-free survival was 10.9 (8.2-14.2) mo in cohort A and 8.3 (5.6-11.1) mo in cohort B. The median (95% CI) overall survival was similar between cohorts (24.3 [18.5-31.8] and 24.1 [17.1-not calculable] mo, respectively). There were no new safety concerns.

[CONCLUSIONS AND CLINICAL IMPLICATIONS] CaboPoint is the first study of pure second-line cabozantinib after first-line CPI-based combinations, providing a benchmark for future second-line aRCC studies.