Abstract
Abstract only
TPS9
Background: Preclinical studies suggest that chemotherapy (CTX) and PARP inhibitors may increase tumor antigenicity, providing a rationale for combined treatment with checkpoint inhibitors in patients (pts) with ovarian cancer (OC). Talazoparib is a potent, orally bioavailable PARP inhibitor with a dual mechanism (PARP trapping and enzyme inhibition) that has shown clinical activity in BRCA-mutated OC and is a US-approved treatment for BRCA-mutated HER2– breast cancer. Avelumab is an anti–PD-L1 checkpoint inhibitor approved for the treatment of metastatic Merkel cell carcinoma and advanced platinum-treated urothelial carcinoma. In phase 1b studies, avelumab showed antitumor activity and acceptable safety in pts with platinum-resistant OC. The JAVELIN Ovarian PARP 100 trial is evaluating the efficacy of avelumab + CTX followed by avelumab + talazoparib maintenance compared with CTX + bevacizumab followed by bevacizumab maintenance in pts with previously untreated epithelial OC. Methods: JAVELIN Ovarian PARP 100 is a phase 3, randomized, open-label, multicenter trial. Eligible pts have previously untreated Stage III-IV epithelial ovarian, fallopian tube, or primary peritoneal cancer; are candidates for platinum-based CTX + bevacizumab; and have completed primary debulking surgery or are candidates for neoadjuvant CTX with planned interval debulking surgery. Approximately 720 pts will be randomized in a 2.5:1:2.5 ratio to receive: CTX (paclitaxel 175 mg/m
2
+ carboplatin AUC 5/6 IV Q3W for 6 cycles) + avelumab (800 mg IV Q3W) followed by avelumab (800 mg Q2W) + talazoparib (0.75 mg QD orally) maintenance for up to 24 months (Arm A); CTX followed by talazoparib (0.75 mg QD) maintenance for up to 24 months (Arm B); or CTX + bevacizumab (15 mg/kg IV Q3W) followed by bevacizumab (15 mg/kg Q3W) maintenance for up to 21 doses or 22 per local approval (Arm C). Pts are stratified by germline BRCA1/2 mutation and resection status. The primary endpoint is progression-free survival (PFS) by blinded independent central review per RECIST v1.1. Other endpoints include overall survival, PFS2, health-related quality of life, and PK. Clinical trial information: NCT03642132.