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)
- Conditions
- Platinum-resistant Ovarian CancerPlatinum-refractory Ovarian CancerPrimary Peritoneal CancerFallopian Tube CancerEndometrioid Ovarian CancerHigh-grade Serous Ovarian CancerOvarian Clear Cell Carcinoma
- Interventions
- Registration Number
- NCT05281471
- Lead Sponsor
- Genelux Corporation
- Brief 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- Female
- Target Recruitment
- 186
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Physician's Choice of Chemotherapy & bevacizumab Bevacizumab (or biosimilar) Physician's Choice of chemotherapy \& bevacizumab (or biosimilar) administered beginning in Week 0. Physician's Choice of chemotherapy includes either a single agent non-platinum chemotherapy, or as platinum chemotherapy is allowed as an option, a platinum-doublet (i.e., platinum agent combined with a non-platinum agent). Olvi-Vec + Platinum-doublet & bevacizumab Bevacizumab (or biosimilar) Olvi-Vec: A total of 2 consecutive days of intraperitoneal catheter infusions in Week 0 Platinum-doublet \& bevacizumab (or biosimilar) administered beginning in Week 4 (preferred), but no later than Week 5 Olvi-Vec + Platinum-doublet & bevacizumab olvimulogene nanivacirepvec Olvi-Vec: A total of 2 consecutive days of intraperitoneal catheter infusions in Week 0 Platinum-doublet \& bevacizumab (or biosimilar) administered beginning in Week 4 (preferred), but no later than Week 5
- Primary Outcome Measures
Name Time Method Progression-free survival (PFS) by RECIST 1.1 in the Intention-to-Treat (ITT) population (all randomized participants regardless of whether they received any dose of treatment) From date of randomization up to 12 months To assess progression-free survival from time of randomization until first documented disease progression based on radiological assessment or death from any cause.
- Secondary Outcome Measures
Name Time Method Incidence of Treatment-emergent Adverse Events in the ITT population From date of first study treatment until death or study completion; assessed up to 36 months Determine safety and tolerability of administering multiple doses of Olvi-Vec via intraperitoneal catheter in combination with platinum-doublet and bevacizumab (or biosimilar) as assessed by CTCAE v. 5.0 following initiation of study treatment until end of study participation.
PFS by RECIST 1.1 in the modified ITT (mITT) population (participants who received at least 1 dose of treatment in either Arm) From date of randomization up to 12 months Time from randomization to first documented disease progression based on radiological assessment or death from any cause.
PFS by iRECIST in the ITT population From date of randomization up to 12 months Time from randomization to first documented disease progression with confirmatory imaging scan performed 4-8 weeks after unconfirmed disease progression or death from any cause.
Duration of Response (DOR) by RECIST 1.1 in the ITT population From date of randomization up to 12 months Time from date of first response until the first date of progressive disease based on radiological assessment.
Overall Response Rate (ORR) by RECIST 1.1 in the ITT population From date of randomization up to 12 months Ratio of the sum of CR \& PR divided by the number of ITT participants from start of treatment to confirmation of response.
Overall Survival in the ITT population From date of randomization until death or study completion; assessed up to 36 months Time from randomization until date of death from any cause.
Trial Locations
- Locations (30)
The University of South Alabama, Mitchell Cancer Institute
🇺🇸Mobile, Alabama, United States
University of Arizona Cancer Center
🇺🇸Tucson, Arizona, United States
City of Hope
🇺🇸Duarte, California, United States
UC San Diego Health - Moores Cancer Center
🇺🇸La Jolla, California, United States
Hoag Gynecologic Oncology
🇺🇸Newport Beach, California, United States
UCI Health Chao Family Comprehensive Cancer Center
🇺🇸Orange, California, United States
AdventHealth Cancer Institute
🇺🇸Orlando, Florida, United States
Women's Cancer Associates with Women's Care Florida
🇺🇸Saint Petersburg, Florida, United States
Sarasota Memorial Research Institute
🇺🇸Sarasota, Florida, United States
Tampa General Hospital/University of South Florida
🇺🇸Tampa, Florida, United States
Indiana University Simon Comprehensive Cancer Center
🇺🇸Indianapolis, Indiana, United States
Holy Cross Hospital
🇺🇸Silver Spring, Maryland, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Mercy Hospital St. Louis
🇺🇸Saint Louis, Missouri, United States
Women's Cancer Center of Nevada
🇺🇸Las Vegas, Nevada, United States
Center of Hope
🇺🇸Reno, Nevada, United States
Stony Brook Cancer Center
🇺🇸Stony Brook, New York, United States
Levine Cancer Institute
🇺🇸Charlotte, North Carolina, United States
East Carolina University
🇺🇸Greenville, North Carolina, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
OhioHealth Research Institute
🇺🇸Columbus, Ohio, United States
Kettering Health
🇺🇸Kettering, Ohio, United States
Oklahoma University Health Stephenson Cancer Center
🇺🇸Oklahoma City, Oklahoma, United States
AHN West Penn Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
Hollings Cancer Center
🇺🇸Charleston, South Carolina, United States
Baylor College of Medicine
🇺🇸Houston, Texas, United States
University of Texas Science Center at Houston, McGovern Medical School
🇺🇸Houston, Texas, United States
Providence Sacred Heart Medical Center & Children's Hospital
🇺🇸Spokane, Washington, United States