Summary
The OnPrime study is a multi-center, randomized open-label phase 3 study evaluating the safety and efficacy of Olvi-Vec followed by platinum-doublet chemotherapy and bevacizumab compared to the Active Comparator Arm with Physician's Choice of chemotherapy and bevacizumab in women diagnosed with platinum-resistant/refractory ovarian cancer (includes fallopian tube cancer and primary peritoneal cancer). This Phase III trial builds on the efficacy and safety data reported in the previous Phase II VIRO-15 trial with promising objective response rate and progression-free survival observed in heavily pre-treated patients with platinum-resistant/refractory ovarian cancer. The phase II results also showed that the intra-peritoneal route of delivery was efficient in generating tumor cell killing and immune activation, and led to clinical reversal of platinum-resistance or refractoriness in this difficult-to-treat patient population.
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Inclusion Criteria: * Histologically confirmed (from prior treatment) non-resectable ovarian, fallopian tube or primary peritoneal cancer. * High-grade serous \[including malignant mixed Mullerian tumor (MMMT) with metastasis that contains high-grade epithelial carcinoma, FIGO grades 2 \& 3 allowed\], endometrioid, or clear-cell ovarian cancer. * Performance status ECOG of 0 or 1. * Life expectancy of at least 6 months. * Received a minimum of 3 prior lines (including the 1st line) of systemic therapy with no maximal limit. * Platinum-resistant or -refractory disease based on platinum-free interval (PFI) from the last dose of the most recent. platinum-based line of therapy (must have received a minimum of 2 doses of platinum in that line) to subsequent disease progression based on radiological assessment. Platinum-refractory: PFI of \< 1 month (including disease progression while on platinum-based therapy). Platinum-resistant: PFI of 1-6 months. * Received prior bevacizumab (or biosimilar) treatment. * No contraindication to receive carboplatin, cisplatin or bevacizumab (or biosimilar). * Have disease progression after last prior line of therapy based on radiological assessment prior to randomization. * At least 1 measurable target lesion per RECIST 1.1 based on abdominal/pelvis imaging scan at screening. * Evidence by CT and/or PET scans or physical exam of abdominal/pelvis region likely having disease in the peritoneal cavity (i.e., peritoneal carcinomatosis). * Adequate renal, hepatic, bone marrow function, adequate coagulation tests, adequate immune function by lymphocyte count. Exclusion Criteria: * Tumors of mucinous, low-grade serous, squamous cell, small cell neuroendocrine subtypes, MMMT tumors absent an epithelial component on recent biopsy, or non-epithelial ovarian cancers (e.g., germ cell tumors, Sex-cord tumors). * Bowel obstruction within last 3 months prior to screening. * Active urinary tract infection, pneumonia, other systemic infections. * Active gastrointestinal bleeding. * Known current central nervous system (CNS) metastasis. * Inflammatory diseases of the bowel. * History of HIV infection. * Active hepatitis B virus or hepatitis C virus within 4 weeks prior to study. * History of thromboembolic event within the prior 3 months. * Contraindications for intraperitoneal (IP) catheter placement: Bowel obstruction with distended abdomen, rigid abdomen with bulky anterior wall carcinomatosis, abdominal wall hernia mesh that precludes laparoscopic entry to abdomen. * Clinically significant cardiac disease at screening (New York Heart Association Class III/IV). * Acute cerebrovascular event(s) such as cerebrovascular accident (CVA) or transient ischemic attack (TIA) in previous 6 months. * Oxygen saturation \<90%. * Received prior virus-based gene therapy or therapy with cytolytic virus of any type. * Receiving concurrent antiviral agent. * Prior malignancy of other histology active within previous 3 years except for locally curable cancers apparently cured such as basal/squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of cervix or breast, any other stage I/II local malignancies. * Received chemotherapy, radiotherapy, other anti-cancer biologic therapies within 4 weeks prior to planned treatment. * Underwent surgery within 4 weeks, or have insufficient recovery from surgical-related trauma or wound healing, prior to first study treatment in either Arm. * Receiving immunosuppressive therapy or steroids (except acute concurrent corticosteroid of no more than 20 mg per day for medical management with prednisolone equivalent. * Symptomatic malignant ascites or pleural effusions defined as rapidly progressive ascites with abdominal distension and gastrointestinal dysfunction, pleural effusions with respiratory difficulties requiring frequent paracentesis \> once every 14 days. * Known hypersensitivity to gentamicin.