MONO-OLA1: A randomized, phase III study of olaparib maintenance monotherapy in patients with BRCA wild-type advanced ovarian cancer following response to first-line platinum-based chemotherapy (334)

Abstract

Objectives: Results of the SOLO1 study (Moore et al. N Engl J Med 2018) led to the approval of the poly(ADP-ribose) polymerase (PARP) inhibitor olaparib in the USA, the EU, Japan, and China as maintenance treatment in patients with a BRCA1 and/or BRCA2 mutation (BRCAm) following response to first-line (1L) platinum-based chemotherapy (PBC). Maintenance PARP inhibitor, with or without bevacizumab, has been shown to provide benefit to patients with newly diagnosed advanced ovarian cancer (OC) without a BRCAm (González-Martin et al. N Engl J Med 2019; Ray-Coquard et al. N Engl J Med 2019). The MONO-OLA1 study (NCT04884360) assesses the efficacy and safety of olaparib maintenance monotherapy when compared with placebo in patients with BRCA wild-type (BRCAwt) advanced OC following response to 1L PBC. Methods: MONO-OLA1 is a Phase III, randomized, double-blind, placebo-controlled, international study. Eligible patients must have higher risk newly diagnosed BRCAwt advanced OC (FIGO stage III/IV) and have a complete response (CR) or partial response (PR) following 1L PBC. Patients with stage III disease who have complete cytoreduction following primary debulking surgery are not eligible. Patients will be randomly assigned (2:1 target, n=420) to receive either olaparib (300 mg bid) or placebo tablets. Randomization will be stratified by response to 1L PBC (CR and PR), homologous recombination deficiency (HRD) status (positive and negative/unknown), and region (China and other international sites). The number of patients with HRD-negative/unknown status will be capped at approximately 60% of the total patient population. The primary endpoints are investigator-assessed progression-free survival (PFS) by RECIST v1.1 in the BRCAwt HRD-positive and BRCAwt groups. A PFS sensitivity analysis by blinded independent central review will be performed to confirm the primary efficacy findings. The key secondary endpoints are second progression-free survival, overall survival, and safety and tolerability. Other secondary endpoints include time to first subsequent therapy or death, time to second subsequent therapy or death, and health-related quality of life. Exploratory endpoints include translational analyses to identify predictive biomarkers of response to olaparib. Enrollment began in May 2021. Objectives: Results of the SOLO1 study (Moore et al. N Engl J Med 2018) led to the approval of the poly(ADP-ribose) polymerase (PARP) inhibitor olaparib in the USA, the EU, Japan, and China as maintenance treatment in patients with a BRCA1 and/or BRCA2 mutation (BRCAm) following response to first-line (1L) platinum-based chemotherapy (PBC). Maintenance PARP inhibitor, with or without bevacizumab, has been shown to provide benefit to patients with newly diagnosed advanced ovarian cancer (OC) without a BRCAm (González-Martin et al. N Engl J Med 2019; Ray-Coquard et al. N Engl J Med 2019). The MONO-OLA1 study (NCT04884360) assesses the efficacy and safety of olaparib maintenance monotherapy when compared with placebo in patients with BRCA wild-type (BRCAwt) advanced OC following response to 1L PBC. Methods: MONO-OLA1 is a Phase III, randomized, double-blind, placebo-controlled, international study. Eligible patients must have higher risk newly diagnosed BRCAwt advanced OC (FIGO stage III/IV) and have a complete response (CR) or partial response (PR) following 1L PBC. Patients with stage III disease who have complete cytoreduction following primary debulking surgery are not eligible. Patients will be randomly assigned (2:1 target, n=420) to receive either olaparib (300 mg bid) or placebo tablets. Randomization will be stratified by response to 1L PBC (CR and PR), homologous recombination deficiency (HRD) status (positive and negative/unknown), and region (China and other international sites). The number of patients with HRD-negative/unknown status will be capped at approximately 60% of the total patient population. The primary endpoints are investigator-assessed progression-free survival (PFS) by RECIST v1.1 in the BRCAwt HRD-positive and BRCAwt groups. A PFS sensitivity analysis by blinded independent central review will be performed to confirm the primary efficacy findings. The key secondary endpoints are second progression-free survival, overall survival, and safety and tolerability. Other secondary endpoints include time to first subsequent therapy or death, time to second subsequent therapy or death, and health-related quality of life. Exploratory endpoints include translational analyses to identify predictive biomarkers of response to olaparib. Enrollment began in May 2021.