An umbrella study of biomarker-driven targeted therapy in patients with platinum-resistant recurrent ovarian cancer: A Korean Gynecologic Oncology Group study (KGOG 3045), AMBITION

Abstract

Background: A pilot study of biomarker-driven targeted therapy in patients with platinum-resistant recurrent ovarian cancer has been started in Korea. Archival tumor samples were tested for HRD and PD-L1 status. Treatment arms will be allocated according to the test results. For HRD+ patients, we tested the synergistic effects of olaparib and other agents; treatment arms will randomly be allocated. (Arm 1: olaparib and cediranib; Arm 2: olaparib and durvalumab). For HRD- patients, we tested the role of biomarker-driven immunotherapy according to PD-L1 expression (Arm 3: durvalumab and chemotherapy in patients with high PD-L1 expression; Arm 4: durvalumab, tremelimumab, and chemotherapy in patients with low PD-L1 expression). Sixty-eight patients will be included from three Korean institutions within 1 year. The primary endpoint is the response rate according to RECIST 1.1 (6 months after treatment initiation). This trial has been registered with clinicaltrials.gov, and the registration number is NCT03699449. Trial design: We designed the present study as biomarker-driven targeted therapy in platinum-resistant recurrent ovarian cancer. Each arm has the following specific hypothesis. Arm 1: olaparib and cediranib have synergistic activity in patients with HRD+. Arm 2: olaparib and durvalumab have synergistic activity in patients with HRD+. Arm 3: durvalumab and chemotherapy (SOC; standard of care) is effective in patients with high PD-L1 expression. Arm 4: durvalumab, tremelimumab, and chemotherapy (SOC; standard of care) have synergistic activity even in patients with low PD-L1 expression. Clinical trial identification: NCT03699449. Legal entity responsible for the study: The authors. Funding(s): Severance Hospital Research Fund for Clinical Excellence and Handok Jeseok Foundation. Disclosure: J. Lee: Research grant / Funding (self): Janssen; Research grant / Funding (institution): MSD; Research grant / Funding (self), Research grant / Funding (institution): AstraZeneca; Research grant / Funding (self): Roche. All other authors have declared no conflicts of interest.Copyright © 2019 European Society for Medical Oncology