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.

Abstract

508 Background: 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 . Clinical outcomes by DepOR subgroup in pts treated with C+N. DepOR Median DOR a (95% CI), months PFS DepOR pop n=234n (%) 48-month b PFS (95% CI), % Median PFS b (95% CI), months OS DepOR popn=293n (%) 48-month b OS (95% CI), % Median OS b (95% CI), months CR NR(30.5, NE) 45 (19) 54(38, 68) NR(30.4, NE) 45 (15) 84(70, 92) NR(NE, NE) PR1 22.1(15.1, 26.0) 25 (11) 12(3, 28) 18.8(13.3, 32.7) 27 (9) 56(35, 72) 51.6(32.2, NE) PR2 21.7(14.1, 30.4) 36 (15) 24(11, 39) 18.9(13.3, 27.4) 38 (13) 67(50, 80) 63.2(47.0, NE) PR3 10.8(7.0, 17.3) 63 (27) 3(0, 13) 9.4(5.5, 17.0) 70 (24) 42(30, 53) 41.9(33.8, 49.5) SD NA 65 (28) 4(1, 11) 5.9(3.9, 10.0) 98 (33) 29(20, 39) 28.7(17.5, 35.0) PD NA NA NA NA 15 (5) 20(5, 42) 11.0(4.8, 25.1) a Calculated in the OS DepOR response (CR or any PR) pop. b From the 6-month landmark.DOR, duration of response; NA, not applicable; NE, not estimable; NR, not reached; pop, population.