Background: The poly (ADP-ribose) polymerase (PARP) inhibitor olaparib is approved for treatment of patients (pts) with germline BRCA mutations (BRCAm) and advanced ovarian cancer (OC). BRCA mutations are genetic alterations leading to homologous recombination deficiency (HRD) and tumor susceptibility to DNA-damaging agents, including PARP inhibitors. Loss of genetic heterozygosity, telomeric-allelic imbalance, or large-scale state transitions may identify additional pts who could benefit from PARP inhibitor therapy. Methods: LIGHT is a non-randomized, open-label, phase 2 study to assess the efficacy and safety of olaparib in patient cohorts identified by different HRD genetic tests (NCT02983799). Patients will have platinum-sensitive (progression > 6 mo after the end of the last platinum-based chemotherapy), relapsed, high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer; ECOG performance status 0–1; and ≥2 prior lines of platinum-based chemotherapy for OC. Key exclusion criteria include prior PARP inhibitor treatment; concomitant use of potent CYP3A4/5 inhibitors or inducers; and symptomatic uncontrolled brain metastases. Patients will be enrolled into 4 cohorts of 30 pts each based upon BRCAm or tumor HRD status determined by genetic test results: germline BRCAm; somatic BRCAm; MyChoice HRD-positive and wildtype BRCAm; MyChoice HRD-negative and wildtype BRCAm. All pts will receive 300 mg olaparib tablets twice daily until disease progression (RECIST v1.1) or unacceptable toxicity. The primary endpoint is investigator-assessed objective response rate (ORR) according to RECIST v1.1 criteria. The maximum precision of the ORR is approximately ±18.7% for 30 pts. Secondary endpoints include duration of response, cancer antigen-125 response rate, disease control rate, progression-free survival, time to any progression, overall survival, and homologous recombination repair gene panel mutation status related to clinical outcome. Planned enrollment of 120 pts at sites in the United States was initiated in December 2016. Clinical trial information: NCT02983799