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NCT05281471PHASE3Recruiting

Efficacy & Safety of Olvi-Vec and Platinum-doublet + Bevacizumab Compared to Physician's Choice of Chemotherapy and Bevacizumab in Platinum-Resistant/Refractory Ovarian Cancer (PRROC) (OnPrime, GOG-3076)

Genelux Corporation

Start Date

8/31/2022

Completion Date

12/1/2027

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.

Detailed Description

Olvi-Vec (olvimulogene nanivacirepvec, aka GL-ONC1, laboratory name: GLV-1h68) is an oncolytic vaccinia virus-based immunotherapy. This study is to test the hypothesis that the combination of Olvi-Vec followed by further chemotherapy is particularly effective against established tumors by virus-mediated immune activation and re-sensitization of tumor cells to chemotherapy. Participant population includes histologically confirmed non-resectable platinum-resistant/refractory ovarian cancer (PRROC). Determination of progression-free survival, safety and overall survival are key objectives. Participants randomized into the Experimental Arm will receive a single-cycle (2 infusions on two consecutive days) of Olvi-Vec through an intraperitoneal catheter. The catheter is then removed, and patients receive systemically administered platinum-doublet chemotherapy and bevacizumab. The control arm receives the Physician's Choice of chemotherapy and bevacizumab at the same dose and schedule. Biological samples will be obtained from some Experimental Arm participants for virus-shedding testing. Assessment of response to treatment in both arms will be by RECIST 1.1 and iRECIST as assessed by Blinded Independent Central Review. Maintenance/continued treatment with non-platinum chemotherapy and bevacizumab is dependent on a participant being clinically stable until confirmed progressive disease by iRECIST or can no longer tolerate therapy. Dr. Robert W. Holloway (AdventHealth Cancer Institute, Orlando, FL) will serve as the National Principal Investigator for this Phase 3 study in PRROC.

Eligibility Criteria

Age Range: 18 years to No maximum

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.

Interventions

BIOLOGICAL

olvimulogene nanivacirepvec

DRUG

Platinum chemotherapy: carboplatin (preferred) or cisplatin

DRUG

Non-platinum chemotherapy: Physician's Choice of gemcitabine, taxane (paclitaxel, docetaxel or nab-paclitaxel) or pegylated liposomal doxorubicin

DRUG

Bevacizumab (or biosimilar)

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Conditions

Platinum-resistant Ovarian CancerPlatinum-refractory Ovarian CancerFallopian Tube CancerPrimary Peritoneal CancerHigh-grade Serous Ovarian CancerEndometrioid Ovarian CancerOvarian Clear Cell Carcinoma

Locations

The University of South Alabama, Mitchell Cancer Institute

Mobile, Alabama 36604

United States

University of Arizona Cancer Center

Tucson, Arizona 85719

United States

City of Hope

Duarte, California 91010

United States

UC San Diego Health - Moores Cancer Center

La Jolla, California 92093

United States

Hoag Gynecologic Oncology

Newport Beach, California 92663

United States

UCI Health Chao Family Comprehensive Cancer Center

Orange, California 92868

United States

AdventHealth Cancer Institute

Orlando, Florida 32804

United States

Sarasota Memorial Healthcare System

Sarasota, Florida 34239

United States

Women's Cancer Associates with Women's Care Florida

St. Petersburg, Florida 33713

United States

Emory University

Atlanta, Georgia 30322

United States

Indiana University Simon Comprehensive Cancer Center

Indianapolis, Indiana 46202

United States

Holy Cross Hospital

Silver Spring, Maryland 20910

United States

University of Michigan

Ann Arbor, Michigan 48109

United States

Karmanos Cancer Institute

Detroit, Michigan 48201

United States

Washington University School of Medicine

St Louis, Missouri 63110

United States

Mercy Hospital St. Louis

St Louis, Missouri 63141

United States

Women's Cancer Center of Nevada

Las Vegas, Nevada 89106

United States

Center of Hope

Reno, Nevada 89511

United States

Stony Brook Cancer Center

Stony Brook, New York 11794

United States

Levine Cancer Institute

Charlotte, North Carolina 28204

United States

East Carolina University

Greenville, North Carolina 27834

United States

Cleveland Clinic

Cleveland, Ohio 44195

United States

OhioHealth Research Institute

Columbus, Ohio 43214

United States

Kettering Health

Kettering, Ohio 45429

United States

ProMedica Flower Hospital

Sylvania, Ohio 43560

United States

Oklahoma University Health Stephenson Cancer Center

Oklahoma City, Oklahoma 73104

United States

AHN West Penn Hospital

Pittsburgh, Pennsylvania 15224

United States

Hollings Cancer Center

Charleston, South Carolina 29425

United States

Erlanger Health, Inc.

Chattanooga, Tennessee 37403

United States

Baylor College of Medicine

Houston, Texas 77030

United States

University of Texas Science Center at Houston, McGovern Medical School

Houston, Texas 77030

United States

Providence Sacred Heart Medical Center & Children's Hospital

Spokane, Washington 99204

United States