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Maintenance therapy with olaparib will be examined in patients with BRCA1/2 wild-type advanced ovarian cancer who responded to first-line, platinum-based chemotherapy in the phase 3 MONO-OLA1 trial.
Maintenance therapy with olaparib (Lynparza) will be examined in patients with BRCA1/2 wild-type advanced ovarian cancer who responded to first-line, platinum-based chemotherapy in the phase 3 MONO-OLA1 trial (NCT04884360), according to a poster presentation at the 2022 SGO Annual Meeting on Womens’ Cancer.1
MONO-OLA1 will access the efficacy and safety of olaparib compared with placebo in patients with newly diagnosed BRCA1/2 wild-type advanced ovarian cancer after a complete response (CR) or partial response (PR) to frontline platinum-based chemotherapy.
Notably, BRCA wild-type disease presents in approximately 60% to 80% of patients with high-grade serous ovarian cancer, and viable treatment options for this patient population remain an unmet need.2 Maintenance therapy with a PARP inhibitor, with or without bevacizumab (Avastin), has demonstrated prior benefit non–BRCA-mutated advanced ovarian cancer.
MONO-OLA1 has a target enrollment of 420 women, who will be randomized 2:1 to receive 300 mg of olaparib tablets twice daily or placebo. Stratification factors will include response to first-line, platinum-based chemotherapy by CR or PR, homologous recombination deficiency (HRD) status, and region (China or other international sites). Notably, patients with HRD-negative or unknown status will be limited to approximately 60% of enrollment to ensure sufficient powering of the primary end point and reflect the real-world prevalence of BRCA wild-type, HRD-positive disease.
The primary end points of MONO-OLA1 are investigator-assessed PFS per RECIST v1.1 for patients with BRCA wild-type, HRD-positive disease, and investigator-assessed PFS per RECIST v1.1 for patients BRCA wild-type disease. Secondary end points include: overall survival; second PFS; time to first subsequent therapy or death; time to second subsequent therapy or death; time to earliest progression per RECIST v1.1, or CA-125, or death; quality of life using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-30 questionnaire and its ovarian-specific module, EORTC QLQ-OV28; and safety. These end points are to be assessed in both BRCA wild-type, HRD-positive and BRCA wild-type patients.
Evaluation of safety and tolerability will include physical examination, laboratory testing, and adverse event reporting, graded according to Common Terminology Criteria for Adverse Events v5.0.
Translational analyses to identify predictive biomarkers of response and resistance to olaparib will be included as an exploratory end point.
Eligible patients must be at least 18 years old with histologically confirmed stage III or IV newly diagnosed high-grade serous or endometrioid ovarian cancer, fallopian tube cancer, or primary peritoneal cancer. For patients with stage III disease, surgical criteria will include primary debulking surgery with macroscopic residual disease following surgery, neoadjuvant chemotherapy, or inoperable disease. For those with stage IV disease, the surgical criteria are primary debulking surgery regardless of residual disease, neoadjuvant chemotherapy, or inoperable disease.
Additionally, patients will be required to have confirmed BRCA wild-type status per centrally performed tumor BRCA testing; clinical CR or PR per RECIST v1.1 criteria following first-line, platinum-based chemotherapy; no prior bevacizumab in combination with chemotherapy or planned bevacizumab maintenance therapy; and a minimum life expectancy of 16 weeks.
Patients will prior exposure to PARP inhibitors, including olaparib, or complete cytoreduction following primary debulking surgery with stage III disease, will be excluded from the trial.
The MONO-OLA1 is currently recruiting patients; the estimated primary completion date of July 2, 2024.3
Previously, results of a primary analysis from the phase 3 SOLO-1 trial (NCT01844986) showed that maintenance olaparib for patients with BRCA-mutant ovarian cancer generated a median progression-free survival (PFS) that was not reached compared with 13.8 months with placebo (HR, 0.30; 95% CI, 0.23-0.41; P < .001).4 Results from SOLO-1 led to the FDA approval of maintenance olaparib in patients with deleterious or suspected deleterious germline or somatic BRCA-mutated advanced epithelial ovarian cancer.