Phase Ib Study Of Avelumab Plus Carboplatin In Patients With Metastatic Castration Resistant Prostate Cancer Progressing After One Line Of Chemotherapy And One Novel Androgen Receptor Axis Inhibitor.

TPS5089 Background: The management of metastatic castration resistant prostate cancer (mCRPC) has been revolutionized with the approval of several agents improving overall survival. However, despite an initial response, most patients will experience disease progression. New studies assessing new agents are still needed. Recently, several immune check-point inhibitors targeting the PD-1 pathway have been approved for the treatment of several solid tumors. However, their use in mCRPC is still at a very early phase of development. The purpose of this study is to test the safety and efficacy of combining carboplatin with avelumab in pretreated mCRPC patients. Genomic aberrations are frequent in CRPC, especially in advanced cases. By selecting pre-treated patients, we will enrich the amount of genetic aberrations (like high mutational burden or DDR mutations) potentially increasing the likelihood of response to avelumab. Cytotoxic chemotherapy like carboplatin has been shown to induce immunogenic tumor cell death, tumor-antigens release and stimulation of the immune system. It has been hypothesized that this “autovaccination” could be enhanced with the addition of immunotherapy such as avelumab. Methods: This is a phase Ib, open-label, single-arm study in patients with mCRPC progressing on at least 1 line of chemotherapy and 1 line of novel androgen receptor axis inhibitors. Inclusion criteria include performance status 0-1 and adequate organ function. Patients will receive 2 cycles of carboplatin AUC5 monotherapy followed by 2 cycles of carboplatin AUC5 plus avelumab 10mg/kg. Maintenance avelumab will continue for up to 2 years. This trial will have 2 stages. In the Safety phase (6 patients) the safety of combining both agents will be analyzed (primary endpoint). If safety is confirmed, an Expansion phase (20 patients) will assess the efficacy of the combination in terms of PSA and radiographic assessment as per PCWG3 (secondary endpoints). As exploratory endpoint, potential immunologic and genomic predictive biomarkers will be analyzed. The trial is open, and enrollment is ongoing. Clinical trial information: 2017-004552-39.