A randomized trial of olaparib, durvalumab, and cancer vaccine, UV1, as maintenance therapy in patients with BRCAwt with recurrent ovarian cancer: ENGOT-OV56/NSGO-CTU-DOVACC trial.

Abstract

TPS5615 Background: Most ovarian cancers (OC) are diagnosed at an advanced stage and despite initial therapy, the disease will often relapse and require further treatment Thus, there is a need for novel therapeutic options. PARP inhibitors lead to increasing tumour neoantigen, and modulation of the tumour microenvironment, which may facilitate a more profound antitumour immune response. UV1 is a therapeutic cancer vaccine directed against telomerase. Since telomerase is an essential enzyme and universally expressed by most tumor cells, it represents a unique cancer antigen as a basis for immunotherapy (IO). The rationale for integrating immunotherapy as maintenance therapy following chemotherapy is based on preclinical studies which have shown that chemotherapy induces immunogenic cell death leading to increased recognition of the tumor by the immune system. The proposed study is evaluating the use of the therapeutic cancer vaccine UV1 in combination with olaparib and the PD-L1 inhibitor, durvalumab as maintenance therapy after response to platinum-based chemotherapy. Methods: The primary objective is to demonstrate efficacy of UV1-olaparib-durvalumab combination maintenance therapy against olaparib in maintenance after platinum combination therapy for BRCAwt patients with relapsed ovarian cancer. Key eligibility criteria include: histologically confirmed, platinim sensitive recurrent OC in response to last platinum-containing chemotherapy, BRCAwt. Patients may be previously treated with PARPi, however prior IO is not permitted. Patients are stratified by HRD status and previous use of PARPi. 184 patients are randomized to three arms (1:1:2): arm A: olaparib single agent, arm B: olaparib-durvalumab and arm C: olaparib, durvalumab-UV1. Duration of therapy: olaparib until progression of disease; durvalumab for 24 months; intradermal UV1, 8 doses within 5 months. Intradermal sargramostim is used as vaccine adjuvant. Primary endpoint is progression-free survival (PFS) of arm C versus arm A. Key secondary endpoints include PFS arm B versus C, patient reported outcomes, and overall survival. This NSGO-CTU sponsored trial is enrolling patients in 11 countries. The following cooperative groups are participating: NSGO-CTU (DK, FIN, NOR, SWE, LTU), BGOG (BE), HeGOG (GRC, CYP), NOGGO (DE), AGO-A (AUT) & DGOG (NL). Clinical trial information: NCT04742075 .