Abstract CT165: A two-stage Simon Design phase II study for NOn-BRCA metastatic BReast cancer (MBC)patients with homologous recombination deficiency treated with OLAparib single agent.(NOBROLA study)
Authors: Aguirre Elena , Amillano Kepa , Cortés Alfonso , Juan María José , Márquez Antonia , Ruiz Manuel , Servitja Sonia , Urrutikoetxea Ander , Llombart Antonio , Perez José , Cortes Javier 
Published: August 2018

Abstract
BACKGROUND: Olaparib is a well-tolerated oral PARP inhibitor. Olaparib has shown promising monotherapy activity in patients with germline mutations in BRCA genes and cancers that exhibited a failure in DNA repair mechanism. The aim of this trial is to evaluate the efficacy of olaparib as single agent in non-BRCA MBC patients whose tumors exhibit an homologous recombination deficiency (HRD) signature.
TRIAL DESIGN: This is an open label, non-randomized, multicenter two-stage phase IIA clinical trial. Patients will receive oral olaparib 300 mg twice a day during 28 days cycles until progression or unacceptable toxicity. HRD signature will be evaluated with one tumor tissue-based test: FMI Lynparza HRR. The stage I principal selection criteria are: (1) Confirmed non-BRCA triple negative locally advance (LA) or MBC; (2) HRD signature; (3) one to three previous lines for the MBC and prior taxanes exposure; (4) RECIST v1.1 evaluable disease. In stage II the study will be extended to patients with luminal subtype and confirmed non-BRCA LA or MBC with HRD signature. The primary goal is to evaluate the efficacy of olaparib monotherapy. Primary endpoint are the clinical benefit rate (CBR), defined as the percentage of patients who experienced overall response (as best response) or stable disease ≥24 weeks in accordance with RECISTv1.1. The trial uses a Simon's minimax two-stage design. We hypothesized that excluding a CBR ≤5% while targeting an improvement of the CBR to ≥20% would be an optimal approach to evaluation of the study strategy. At first stage, ≥1 patient with clinical benefit among 17 patients will be necessary to continue. At the study end, ≥5 subjects with clinical benefit out of 35 evaluable subjects are required to justify this strategy in further clinical trials. Considering a drop-out rate of 10%, a sample size of 39 patients will be needed to attain 80% power at nominal level of one-sided alpha of 0.05. We anticipate a 40% of screened TNBC and 25% of luminal (RH-positive HER2-negative) non-BRCA patients will exhibit HRD signature. Therefore, we expect to screen 48 patients in the 1st stage and 80 patients in the 2nd stages to accomplish with the accrual goal (a total of 128 patients screened). Secondary objectives include (1) efficacy measures: objective response rate (ORR), progression-free survival (PFS) and overall survival; (2) the assessment of HRD signatures agreement and validity to predict clinical benefit and overall response; and (3) safety-related outcomes.
Citation Format: Elena Aguirre, Kepa Amillano, Alfonso Cortés, María José Juan, Antonia Márquez, Manuel Ruiz, Sonia Servitja, Ander Urrutikoetxea, Antonio Llombart, José Perez, Javier Cortes. A two-stage Simon Design phase II study for NOn-BRCA metastatic BReast cancer (MBC)patients with homologous recombination deficiency treated with OLAparib single agent.(NOBROLA study) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr CT165.