In this open-label, multicenter phase II trial, mCRPC patients in two cohorts (cohort 1: asymptomatic or minimally symptomatic, who had progressed after at least 1 second generation hormone therapy with no prior chemotherapy; cohort 2: progression after chemotherapy) were treated with Nivo 1mg/kg + IPI 3mg/kg Q 3 weeks for 4 doses, then Nivo 480mg Q 4 weeks. Treatment was continued until progression or unacceptable toxicity. Endpoints included objective response, overall survival, safety, PSA response, and biomarker analysis. Median follow up at this analysis for cohort 1 was 11.9 months and 13.5 months for cohort 2.
Patient in both cohorts had similar baseline characteristics, including previous treatment with abiraterone and/or enzalutamide. Cohort 2 patients had a greater number of bone metastases. Overall response rates were 26% and 10% in cohort 1 and 2, respectively, including 2 patients in each cohort who had a complete response. Median time to response was approximately 2 months. PSA response rate was 18% in cohort 1 and 10% in cohort 2.
In an exploratory biomarker subgroup analysis, overall response rates were higher in patients with greater PD-L1 mutational rate (>1%), DNA damage repair, homologous recombination deficiency or above mediation tumor mutation burden. Of the patients who had an objective response, these patients had tumors positive for BCRA2, FANCA, ERCC3, ATRX, XRCC2, and MLH1. In cohort 1, patients with higher PSA response was also correlated with greater PD-L1 mutational Rate (>1%), however, it was not associated with the response rate in cohort 2. Median overall survival was 19 months in cohort 1 and 15 months in cohort 2.
All grade treatment-related adverse effects were very common with rates >93% in both cohorts. Grade 3-5 adverse effects were present in 42% and 53% of patients in cohort 1 and 2, respectively. Most common high-grade AEs were primarily gastrointestinal.
In conclusion, this thought-provoking data may provide an impetus for more immunotherapy combination trials. Preliminary data suggest that biomarkers may have prognostic value, but further studies are necessary. We look forward to the final results of this trial being released in the years to come.
Presented by: Padmanee Sharma, MD Ph.D., Department of Genitourinary Oncology, MD Anderson Cancer Center, Houston, Texas
Written by: David B. Cahn, DO, MBS, @dbcahn, Fox Chase Cancer Center at the 2019 American Society of Clinical Oncology Genitourinary Cancers Symposium, (ASCO GU) #GU19, February 14-16, 2019 - San Francisco, CA