Characterization of depth and durability of response in patients (pts) with previously untreated advanced renal cell carcinoma (aRCC) who received cabozantinib plus nivolumab (C+N): Long-term follow-up and exploratory analysis of CheckMate 9ER.

C+N is approved as first-line treatment in aRCC based on the CheckMate 9ER trial, which demonstrated superior progression-free survival (PFS) and overall survival (OS) versus sunitinib in this pt population. In this exploratory, post hoc analysis, we characterized the depth and durability of response with long-term follow-up (based on the final analysis of CheckMate 9ER) in pts receiving C+N. Methods: Pts received C (40 mg) once daily plus N (240 mg) every 2 weeks. Depth of response (DepOR) subgroups were based on best overall response (blinded independent central review [BICR] per RECIST v1.1) and best tumor reduction threshold, as follows: complete response (CR); partial response subdivided by a tumor reduction of ≥80% (PR1), ≥60%–<80% (PR2), or ≥30%–<60% (PR3); stable disease (SD); and progressive disease (PD). PFS (per BICR) and OS were analyzed by DepOR subgroups after a 6-month post-randomization landmark. Results: Of 323 pts randomized to C+N, 293 pts were alive, and 234 pts were alive and progression-free at the 6-month landmark and were categorized by DepOR subgroup. With a median follow-up of 67.6 months (range: 60.2–80.2), pts with a CR exhibited a durable response and prolonged benefit in DOR, PFS, and OS (Table). Pts who experienced a response (CR or any PR) included those with liver metastases (16%– 29%), sarcomatoid features (6%–15%), ≥2 metastatic sites (60%–78%), and poor IMDC risk (7%–17%). Median duration of therapy was 30.4 (CR), 29.9 (PR1), 35.6 (PR2), 23.0 (PR3), 15.3 (SD), and 9.0 (PD) months. Any-grade treatment-related adverse events were generally consistent across DepOR subgroups. Conclusions: This exploratory analysis of CheckMate 9ER revealed durable responses in pts who experienced a CR. Pts who responded to treatment (CR or any PR) included those with poor prognostic characteristics. Clinical trial information: NCT03141177.[Table