LBA52Efficacy and safety of nivolumab in combination with docetaxel in men with metastatic castration-resistant prostate cancer in CheckMate 9KD

Abstract Background The antitumor activity of programmed death-1 (PD-1)/PD-1 ligand 1 (PD-L1) inhibition alone is limited in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC). Combining immunotherapy with standard-of-care chemotherapy could improve outcomes in mCRPC. We report interim analysis results for the nivolumab + docetaxel (NIVO+DOCE) treatment arm from CheckMate 9KD. Methods CheckMate 9KD is a phase II study of NIVO in combination with DOCE, rucaparib, or enzalutamide. Eligible pts had confirmed metastatic adenocarcinoma of the prostate, ongoing androgen deprivation therapy, and evaluable tumor biopsy. Pts assigned to NIVO+DOCE (chemotherapy-naïve and received ≤2 prior second-generation hormonal therapies) received NIVO 360 mg every 3 weeks + DOCE 75 mg/m2 every 3 weeks + prednisone 5 mg twice daily for ≤10 cycles followed by NIVO 480 mg every 4 weeks alone until disease progression or unacceptable toxicity (up to 2 years). Coprimary endpoints were objective response rate (ORR) and prostate-specific antigen response rate (PSA-RR; defined as ≥ 50% PSA reduction from baseline). Secondary endpoints included radiographic progression-free survival (rPFS), and safety/tolerability in all treated pts. Association of biomarkers with efficacy was an exploratory endpoint. Results This interim analysis included 41 pts in the NIVO+DOCE arm with a minimum follow-up of 28 weeks, of whom 19 (46.3%) had measurable disease. At the time of the analysis, 24 (58.5%) had discontinued study treatment. ORR in pts with measurable disease was 36.8% (95% confidence interval [CI], 16.3–61.6) with 1 complete response and 6 partial responses. Confirmed PSA-RR was 46.3% (95% CI, 30.7–62.6). Median rPFS was 8.2 months (95% CI, 6.6–not estimable). The 6-month rPFS rate was 71.5%. Any-grade and grade 3/4 treatment-related adverse events occurred in 92.7% and 48.8% of pts, respectively. Associations of biomarkers are also evaluated. Conclusions The combination of NIVO+DOCE showed encouraging clinical activity in pts with mCRPC, with a safety profile consistent with those of the individual agents. A phase III trial is warranted to further evaluate NIVO+DOCE in mCRPC. Clinical trial identification NCT03338790. Editorial acknowledgement Professional medical writing assistance was provided by Nicolette Belletier, PhD, of Parexel, and funded by Bristol-Myers Squibb. Legal entity responsible for the study Bristol-Myers Squibb. Funding Bristol-Myers Squibb and On