171TiPPhase II study of olaparib in previously treated advanced solid tumours with homologous recombination repair mutation (HRRm) or homologous recombination repair deficiency (HRD): LYNK-002

AbstractBackgroundPoly(ADP-ribose) polymerases (PARPs) play a key role in DNA damage repair (DDR). DDR defects due to HRRm (eg BRCA mutation [BRCAm]) or resulting in HRD (eg global loss of heterozygosity) may sensitize tumors to PARP inhibitors, eg olaparib. Olaparib monotherapy has activity in BRCAm ovarian, breast, pancreatic, and prostate cancer, and in prostate cancer with DDR defects beyond BRCAm (TOPARP). Olaparib improved efficacy outcomes vs placebo/chemotherapy as treatment in  ≤ 3rd-line (3L) HER2-negative BRCAm breast cancer (OlympiAD) and ≥2L BRCAm ovarian cancer (SOLO3), and maintenance therapy in ≥ 1L ovarian cancer irrespective of BRCAm (SOLO1, Study 19). LYNK-002 (NCT03742895) evaluates HRRm/HRD positivity (HRD+; per Lynparza HRR-HRD assay, Foundation Medicine, Inc., Cambridge, MA) as biomarkers of tumor-agnostic response to olaparib.Trial designThis open-label, phase 2 study will enroll ∼370 patients (pts) ≥18 y with previously treated, histologically/cytologically confirmed HRRm/HRD + (per Lynparza HRR-HRD assay) advanced solid tumors who failed/are intolerant to/ineligible for available SOC and have no PD during prior platinum-based treatment (any number of prior regimens ), measurable disease per RECIST v1.1/Prostate Cancer Working Group (PCWG)-modified RECIST v1.1, no CNS metastases, ECOG PS 0–1, and no persistent toxicity from prior therapy. Newly obtained/archival tumor samples will be centrally evaluated using the Lynparza HRR-H...
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research