Abstract CT178: Olaparib plus pembrolizumab in patients with previously treated advanced solid tumors with homologous recombination repair mutation (HRRm) and/or homologous recombination deficiency (HRD): Initial results of the phase 2 KEYLYNK-007 study

2021 ◽  
Author(s):  
Michele Maio ◽  
Ronnie Shapira-Frommer ◽  
Timothy A. Yap ◽  
Tudor Ciuleanu ◽  
Henry Gomez ◽  
...  
Keyword(s):  
Homologous Recombination ◽  
Solid Tumors ◽  
Homologous Recombination Repair ◽  
Advanced Solid Tumors ◽  
Phase 2 ◽  
Homologous Recombination Deficiency ◽  
Recombination Repair ◽  
Previously Treated ◽  
Initial Results

318 Olaparib plus pembrolizumab in patients with previously treated advanced solid tumors with homologous recombination repair mutation and/or homologous recombination repair deficiency: KEYLYNK-007

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A344-A344
Author(s):  
Timothy A Yap ◽  
Mallika Dhawan ◽  
Andrew E Hendifar ◽  
Michele Maio ◽  
Taofeek K Owonikoko ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Homologous Recombination ◽  
Antitumor Activity ◽  
Solid Tumors ◽  
Homologous Recombination Repair ◽  
Advanced Solid Tumors ◽  
Repair Deficiency ◽  
Recombination Repair ◽  
Modified Recist ◽  
Previously Treated

BackgroundTreatment with the anti–PD-1 antibody pembrolizumab has improved clinical outcomes in multiple previously treated advanced solid tumors. The poly (ADP-ribose) polymerase (PARP) inhibitor olaparib has shown antitumor activity as monotherapy in patients with previously treated advanced ovarian, breast, pancreatic, and prostate cancers with BRCA1/BRCA2 mutations (BRCAm). Activity was also seen in patients with previously treated advanced solid tumors with other homologous recombination repair mutation (HRRm) and in those with ovarian cancer with homologous recombination repair deficiency (HRD) phenotype. PARP inhibitors have been found to increase interferon signaling and tumor infiltrating lymphocytes, enhancing tumor susceptibility to immune checkpoint blockade. Antitumor activity of PD-(L)1 plus PARP inhibition was found to be higher than expected with either agent alone in patients with recurrent ovarian cancer regardless of BRCAm or HRD status and in patients with BRCAm breast cancer. KEYLYNK-007 (NCT04123366) evaluates the antitumor activity and safety of olaparib in combination with pembrolizumab in patients with previously treated advanced solid tumors with HRRm and/or HRD.MethodsThis phase 2, nonrandomized, multicenter, open-label study will enroll approximately 300 patients aged ≥18 years 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), with an ECOG PS of 0-1. Patients will be grouped by biomarker status: subgroup 1: BRCAm; subgroup 2: HRRm without BRCAm; and subgroup 3: HRD positive without HRRm (loss of heterozygosity score ≥16 per Lynparza HRR-HRD assay). Patients will receive olaparib 300 mg twice daily + pembrolizumab 200 mg intravenously Q3W (35 cycles) until PD, unacceptable AEs, intercurrent illness, investigator decision, withdrawal of consent, 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 months, then Q12W until PD, start of new anticancer treatment, withdrawal of consent, pregnancy, or death. AEs will be monitored throughout the study and for 30 days after final dose (90 days for serious AEs). The primary endpoint is ORR (RECIST v1.1 or PCWG–modified RECIST version 1.1 by BICR). Secondary endpoints include duration of response (DOR) and PFS (RECIST v1.1 or PCWG–modified RECIST v1.1 by BICR), OS, and safety. Point estimate and exact Clopper-Pearson CI for ORR, and Kaplan-Meier estimates for DOR, PFS, and OS will be calculated. A total of 89 sites are currently enrolling in 20 countries.ResultsN/AConclusionsN/ATrial RegistrationClinicalTrials. gov identifier, NCT04123366Ethics ApprovalAn independent institutional review board or ethics committee approved the protocol at each study site, and the trial is being conducted in compliance with Good Clinical Practice guidelines and the Declaration of Helsinki.

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.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS3156-TPS3156 ◽  
Author(s):  
Timothy A Yap ◽  
Mallika Sachdev Dhawan ◽  
Andrew Eugene Hendifar ◽  
Michele Maio ◽  
Taofeek Kunle Owonikoko ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Ovarian Cancer ◽  
Homologous Recombination ◽  
Antitumor Activity ◽  
Solid Tumors ◽  
Homologous Recombination Repair ◽  
Advanced Solid Tumors ◽  
Recombination Repair ◽  
Modified Recist ◽  
Previously Treated

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 .

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