ENGOT-OV43/KEYLYNK-001: A phase III, randomized, double-blind, active- and placebo-controlled study of pembrolizumab plus chemotherapy with olaparib maintenance for first-line treatment of BRCA-nonmutated advanced epithelial ovarian cancer
| Autor: | M Puglisi, Ignace Vergote, Qi Liu, Vanda Salutari, Robert M. Wenham, Stephanie Lheureux, Chyong-Huey Lai, Patricia Pautier, Stephen Michael Keefe, Antonio González-Martín, Radoslaw Madry, Paolo Zola, David Cibula, Jacob Korach, Samet Topuz, Jalid Sehouli, Kosei Hasegawa, Byoung-Gie Kim |
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| Rok vydání: | 2019 |
| Předmět: |
Oncology
Cancer Research medicine.medical_specialty Chemotherapy business.industry medicine.medical_treatment Placebo-controlled study Pembrolizumab Olaparib Double blind First line treatment 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine chemistry 030220 oncology & carcinogenesis Internal medicine PARP inhibitor medicine Epithelial ovarian cancer business 030215 immunology |
| Zdroj: | Journal of Clinical Oncology. 37:TPS5603-TPS5603 |
| ISSN: | 1527-7755 0732-183X |
| Popis: | TPS5603 Background: There is a significant unmet need to develop new regimens for BRCA1/2-nonmutated advanced ovarian cancer (OC). The PARP inhibitor olaparib is approved for women with platinum-sensitive, recurrent OC regardless of BRCA1/2 status and, more recently, for newly diagnosed women with BRCA-mutated OC. In the TOPACIO/KEYNOTE-162 study, the combination of the PD-1–blocking antibody pembrolizumab (pembro) and niraparib demonstrated efficacy in platinum-resistant relapsed OCirrespective of BRCA1/2 status. ENGOT-OV43/KEYLYNK-001 (ClinicalTrials.gov, NCT03740165) is a phase 3, randomized, double-blind, active- and placebo-controlled study of pembro plus paclitaxel-carboplatin chemotherapy (CT) followed by olaparib maintenance for first-line treatment of patients with BRCA1/2-nonmutated advanced epithelial OC (EOC). Methods: Patients with stage III or IV BRCA-nonmutated EOC, primary peritoneal cancer, or fallopian tube cancer will be stratified by surgery status (no residual tumor after primary debulking surgery [PDS], residual tumor after PDS, or planned interval debulking), bevacizumab use, and PD-L1 status (combined positive score < 10 or ≥10). After one lead-in cycle of CT, patients will be randomized 1:1:1 to receive: CT + pembro followed by olaparib maintenance; CT + pembro followed by placebo; or CT + placebo followed by placebo. The CT regimen will be administered for 5 cycles, and pembro 200 mg Q3W will be administered for 35 infusions. Olaparib 300 mg BID maintenance therapy will start after the end of CT as concomitant treatment with pembro until discontinuation or for 2 years if the patient has a complete response. Bevacizumab use is permitted at investigator’s discretion and determined prerandomization. Primary endpoints are investigator-assessed progression-free survival (PFS) per RECIST 1.1 criteria and overall survival. Key secondary endpoints are PFS per RECIST 1.1 assessed by blinded independent central review, PFS after next-line treatment, and safety. Enrollment is currently ongoing. Clinical trial information: NCT03740165. |
| Databáze: | OpenAIRE |
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