SOLO3: A randomized phase III trial of olaparib versuschemotherapy in platinum-sensitive relapsed ovarian cancer patients with a germline BRCA1/2 mutation (gBRCAm).

TPS5598 Background: Olaparib (Lynparza) is a PARP inhibitor that can induce synthetic lethality in cancer cells with a deleterious BRCA mutation. A subgroup analysis of data from a Phase II trial of olaparib monotherapy in patients with a gBRCAm (Study 42; NCT01078662) demonstrated an objective response rate (ORR) of 46% in a small number of patients with platinum-sensitive ovarian cancer who were heavily pretreated ( ≥ 3 prior chemotherapy regimens) (Domchek et al, ASCO 2015). The approval of olaparib monotherapy (400 mg bid; capsules) in the US, based on Study 42 data, for patients with gBRCAm advanced ovarian cancer who have received ≥ 3 lines of prior chemotherapy has led to initiation of this AstraZeneca-sponsored Phase III trial in platinum-sensitive ovarian cancer patients (SOLO3; NCT02282020). Methods: SOLO3 is an open-label, randomized, controlled, multicenter study that will assess the efficacy and safety of olaparib monotherapy, compared with standard chemotherapy, in patients with relapsed high-grade serous or endometrioid ovarian cancer. Eligibility also requires a predicted deleterious gBRCAm, completion of ≥ 2 lines of platinum-based chemotherapy, and at least partial platinum sensitivity (progression ≥ 6 months after completion of the last platinum-based chemotherapy). All patients will undergo gBRCA testing (Myriad Integrated BRACAnalysis) as part of the trial. Approximately 411 subjects will be randomized (2:1) to either olaparib (300 mg bid; tablets) or physician’s choice of a single standard chemotherapy agent. The primary endpoint is progression-free survival (PFS), which will be evaluated by blinded independent central review using RECIST v1.1. Tumor assessments will be performed at baseline using CT or MRI, followed by measurements every 8 weeks for 48 weeks, and then every 12 weeks. The primary analysis will commence following ~288 PFS events (~70% maturity) using a stratified log-rank test. Other endpoints include: overall survival; time from randomization to second progression (PFS2); ORR; health-related quality of life; and safety and tolerability. Enrollment began on 6 February 2015. Clinical trial information: NCT02282020.