CRI-CCTG-0003/IND.240: An immunotherapy platform study in platinum-resistant high grade serous ovarian cancer (IPROC).

Abstract

TPS5617 Background: Identifying new treatments for patients with platinum-resistant high grade serous ovarian cancer (HGSC) is a priority. Although several biological features of HGSC suggest inherent immunogenicity, immunotherapy has had limited efficacy to date. IPROC is an adaptive platform trial designed to evaluate multiple immunotherapy combinations selected and informed by an expert panel. IPROC accommodates both biomarker-agnostic and biomarker-directed combinations. Protocol and sub study specific translational studies are conducted on archived diagnostic tissue and serial prospective blood and tumor sample collection. Methods: IPROC is an open-label, multi center, phase II platform trial. Eligibility includes HGSC histology; progression within 6 months of the last platinum regimen; <1 prior line of chemotherapy for platinum resistant disease (unlimited prior lines for platinum sensitive); prior treatment with immunotherapy allowed (provided not discontinued for toxicity), ECOG 0/1. Patients must be willing and able to undergo study procedures. The primary endpoint is ORR (RECIST1.1). Secondary endpoints include iRECIST ORR, RECIST/iRECIST progression free and overall survival and safety. Exploratory objectives include whole exome sequencing and immune profiling of tumor and blood samples to identify biomarkers and new immunotherapy strategies/combinations for future evaluation. Tumor biopsy occurs at baseline, cycle 2 and progression (voluntary) with blood and plasma collected at each cycle and on progression. All sub studies use Simon 2-stage design with 10 patients (pts) enrolled in each stage. At the end of stage 1, in the absence of response, a modified cohort based on biomarker selection may be created through protocol amendment. In each substudy a null hypothesis that the objective response rate (ORR) is ≤5% is tested against a one-sided alternative that the ORR is ≥ 25%. A combination would be accepted as active if ≥4/20 pts respond with α=0.02 and power of 0.76. As of January 19, 2023, 2 sub studies are open and 12 patients have accrued. Sub study A is evaluating the combination of durvalumab and BA3011, a conditionally active anti-AXL humanized monoclonal antibody (IgG1) conjugated to monomethyl auristatin E (MMAE) in AXL overexpressing HGSC. Sub study B is evaluating durvalumab plus BA3021, a CAB anti-receptor tyrosine kinase orphan receptor 2 (ROR2) humanized monoclonal antibody (IgG1) conjugated to MMAE in ROR2 overexpressing HGSC. Further sub studies are planned (NCT04918186). Clinical trial information: NCT04918186 .