CheckMate 9KD Arm B final analysis: Efficacy and safety of nivolumab plus docetaxel for chemotherapy-naïve metastatic castration-resistant prostate cancer.

Abstract

12 Background: CheckMate 9KD (NCT03338790) is a phase 2 trial of nivolumab (NIVO; anti-PD-1) in combination with rucaparib, docetaxel (DOCE), or enzalutamide for patients with metastatic castration-resistant prostate cancer (mCRPC). DOCE is a standard-of-care chemotherapy for mCRPC that may potentiate antitumor immune responses, thus supporting its use in combination with NIVO, which has shown limited antitumor activity in mCRPC as monotherapy. We report final analysis results for Arm B (NIVO + DOCE) of CheckMate 9KD. Methods: Arm B enrolled patients with chemotherapy-naive mCRPC with ongoing androgen deprivation therapy and ≤ 2 prior novel antiandrogen therapies (NATs; i.e., abiraterone, enzalutamide, etc.). Patients received NIVO 360 mg + DOCE 75 mg/m2 Q3W + prednisone 5 mg BID for ≤ 10 cycles, followed by NIVO 480 mg Q4W until disease progression/unacceptable toxicity (up to 2 years). Coprimary endpoints were objective response rate (ORR) and prostate-specific antigen response rate (PSA-RR; defined as a ≥ 50% PSA reduction). Secondary endpoints included radiographic progression-free survival (rPFS), overall survival (OS), and safety. Results: Of 84 treated patients with a median age of 71 years (range: 53-88), 27% had visceral disease and 54% had measurable disease. The median number of docetaxel cycles was 8; the median number of nivolumab doses was 11. Median follow up was 15.2 months. The table displays the efficacy outcomes, which appear to show comparable ORR in patients receiving versus not receiving prior NAT. There was 1 (2.2%) complete objective response and 17 (37.8%) partial responses in 45 patients with measurable disease. Any-grade treatment-related AEs (TRAEs) occurred in 95.2% of patients, most commonly fatigue (39.3%), diarrhea (35.7%), and alopecia (34.5%). Grade 3-4 TRAEs occurred in 47.6% of patients, most commonly neutropenia (16.7%). TRAEs led to discontinuation in 29.8% of patients. The most common immune-related AEs were GI (35.7%) or skin-related (26.2%). There were 3 treatment-related deaths (1 pneumonitis related to NIVO; 2 pneumonias related to DOCE). Conclusions: NIVO + DOCE has encouraging clinical activity in patients with chemotherapy-naïve mCRPC, regardless of prior NAT, with a safety profile consistent with those of the individual agents. These outcomes support the ongoing phase 3 CheckMate 7DX trial of NIVO + DOCE vs placebo + DOCE for mCRPC (NCT04100018). Clinical trial information: NCT03338790. [Table: see text]