A phase II study of olaparib in combination with pembrolizumab in patients with previously treated advanced solid tumors with homologous recombination repair mutation (HRRm) and/or homologous recombination repair deficiency (HRD): KEYLYNK-007.

Abstract

TPS3156 Background: The anti-PD-1 antibody pembrolizumab (pembro) has improved clinical outcomes in multiple previously treated advanced solid tumors. The poly (ADP-ribose) polymerase (PARP) inhibitor olaparib (ola) has shown antitumor activity as monotherapy in previously treated advanced cancers with BRCA1/ BRCA2 mutations (BRCAm), other HRRm, and ovarian cancer with HRD phenotype. Antitumor activity of PD-(L)1 plus PARP inhibition was reportedly higher than expected with either agent alone in patients (pts) with recurrent ovarian cancer regardless of BRCAm or HRD status and in pts with BRCAm breast cancer. KEYLYNK-007 (NCT04123366) evaluates antitumor activity and safety of ola plus pembro in pts with advanced solid tumors with HRRm and/or HRD. Methods: This phase 2, nonrandomized, multicenter, open-label study plans to enroll ~300 pts aged ≥18 y with histologically/cytologically confirmed, previously treated, advanced solid tumors with HRRm and/or HRD per Lynparza HRR-HRD assay (Foundation Medicine, Inc., Cambridge, MA, USA) and ECOG PS 0-1. Pts will be grouped by biomarker status: (1) BRCAm; (2) HRRm without BRCAm; (3) HRD positive without HRRm (loss of heterozygosity score ≥16 per Lynparza HRR-HRD assay). Pts will receive ola 300 mg BID + pembro 200 mg IV Q3W (35 cycles) until PD, unacceptable AEs, intercurrent illness, investigator decision, withdrawal, or pregnancy. Tumor imaging assessment by blinded independent central review (BICR) per RECIST v1.1 or Prostate Cancer Working Group (PCWG)-modified RECIST v1.1 for prostate cancer will occur Q9W for 12 mo, then Q12W until PD, start of new anticancer treatment, withdrawal, pregnancy, or death. AEs will be monitored throughout the study and for 30 days after final dose (90 days for serious AEs) and graded by NCI CTCAE v5. The primary endpoint is ORR (RECIST v1.1 or PCWG-modified RECIST v1.1 by BICR). Secondary endpoints include DOR, PFS (RECIST v1.1 or PCWG-modified RECIST v1.1 by BICR), OS, and safety. ORR will be analyzed by the Clopper-Pearson method; and DOR, PFS, and OS by the Kaplan-Meier method. Clinical trial information: NCT04123366 .