Chemoimmunotherapy for Aggressive Variant Prostate Cancers (AVPC)
Abstract
Men with androgen indifferent prostate cancers have a dismal prognosis and limited treatment options. To provide a framework for their study and therapy development, we defined the aggressive variant prostate cancers (AVPC) and in previous studies obtained evidence that men with AVPC benefit from the addition of carboplatin to cabazitaxel chemotherapy, and likely from PARP inhibitor maintenance following chemotherapy induction. Building on this work and based on the evidence of immune-modulation by chemotherapy and PARP inhibitors in preclinical studies, as well as the clinical benefit observed with the addition of immune-checkpoint therapy to chemotherapy in patients with aggressive malignancies that share similarities with the AVPC, we hypothesized that PD-1 inhibition will enhance the anti-tumor response of platinum-based chemotherapy induction and PARP inhibitor maintenance in men with AVPC. To test this hypothesis, we proposed this phase II randomized trial in which men with AVPC are treated with up to 6 cycles of cabazitaxel-carboplatin induction, with the anti-PD1 inhibitor cetrelimab added on Cycle no. 2 of treatment, and then randomized to the PARP inhibitor niraparib vs niraparib plus cetrelimab maintenance. Tumor biopsies are mandated at 3 timepoints. Our primary objectives are to estimate the progression free survival of men with AVPC in each arm and evaluate the changes in the density and localization of immune markers and cell subsets in tumor biopsies. The study was activated on 12/29/2020. As of 09/16/2021,23 patients have been registered and 28 tissue samples have been assembled.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2021
- Accession Number
- AD1154970
Entities
People
- Ana Aparicio
Organizations
- The University of Texas MD Anderson Cancer Center