(UroToday.com) The CheckMate 9KD trial is a multi-arm open label phase 2 study evaluating the efficacy of the anti-PD-1 antibody nivolumab in combination with other therapies such as docetaxel, rucaparib or enzalutamide in metastatic castration-resistant prostate cancer (mCRPC). The rationale for the combination of nivolumab with docetaxel is that docetaxel is a standard of care therapy for mCRPC that may potentiate anti-tumor immune responses. Prior analysis of this combination at ESMO 2019 demonstrated a 37% overall response rate with one complete response and six partial responses. The study schema is shown below. The co-primary endpoints are overall response rate (investigator reports) and PSA response rate (>= 50% decrease).
In total, 84 patients were treated in this cohort, and results are presented at a median follow-up of 15.2 months. A median of 11 nivolumab doses and 8 docetaxel doses were given to the study participants. By July 2020, 90% of patients had discontinued treatment, mainly because of disease progression or drug toxicity, with 8 patients remaining on study at the time of data lock. Patient characteristics are summarized below. 
The overall response rate was 40%, which was similar regardless of prior novel androgen therapy. PSA response rate was 46.9% overall and was higher (60.7%) in patients without prior novel hormonal therapy relative to 39.6% who had received prior hormonal therapy. In total, 80% of patients had some reduction in tumor size, and 84% of patients experienced a drop in their PSA. The median rPFS was 9 months, and the median overall survival was 18.2 months. Both rPFS and OS were numerically higher in patients who had not received prior novel anti-androgen therapy.
Almost 30% of patients discontinued one or both study drugs, most commonly due to pneumonitis, peripheral neuropathy, or fatigue. There were three treatment-related deaths, one from nivolumab associated pneumonitis and two from docetaxel associated pneumonia. A table of all treatment-related adverse events is shown below. 
Dr. Fizazi ended by concluding that the combination of nivolumab and docetaxel showed encouraging clinical activity in patients with mCRPC. Biomarker analyses are ongoing to investigate potential markers of response. The CheckMate 7DX trial is currently ongoing as a randomized phase 3 study of docetaxel and prednisone with or without nivolumab therapy in mCRPC.
Presented by: Karim Fizazi, MD, Ph.D., Head of the Department of Cancer Medicine at the Institut Gustave Roussy, Villejuif, France and Professor of Oncology at the University of Paris
Written by: Alok Tewari, MD, PhD, Medical Oncologist at the Dana-Farber Cancer Institute, during the 2021 American Society of Clinical Oncology Genitourinary Cancers Symposium (#GU21), February 11th-February 13th, 2021
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Nivolumab Plus Docetaxel for Chemotherapy-Naïve Metastatic Castration-Resistant Prostate Cancer from Checkmate 9KD Arm B, - Karim Fizazi