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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
186
Olvi-Vec is an engineered oncolytic vaccinia virus
Administered according to local practice
Administered according to local practice
Administered according to local practice
The University of South Alabama, Mitchell Cancer Institute
Mobile, Alabama, United States
RECRUITINGUniversity of Arizona Cancer Center
Tucson, Arizona, United States
RECRUITINGCity of Hope
Duarte, California, United States
RECRUITINGUC San Diego Health - Moores Cancer Center
La Jolla, California, United States
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)
To assess progression-free survival from time of randomization until first documented disease progression based on radiological assessment or death from any cause.
Time frame: From date of randomization up to 12 months
Incidence of Treatment-emergent Adverse Events in the ITT population
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.
Time frame: From date of first study treatment until death or study completion; assessed up to 36 months
Duration of Response (DOR) by RECIST 1.1 in the ITT population
Time from date of first response until the first date of progressive disease based on radiological assessment.
Time frame: From date of randomization up to 12 months
PFS by RECIST 1.1 in the modified ITT (mITT) population (participants who received at least 1 dose of treatment in either Arm)
Time from randomization to first documented disease progression based on radiological assessment or death from any cause.
Time frame: From date of randomization up to 12 months
PFS by iRECIST in the ITT population
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.
Time frame: From date of randomization up to 12 months
Overall Response Rate (ORR) by RECIST 1.1 in the ITT population
Ratio of the sum of CR \& PR divided by the number of ITT participants from start of treatment to confirmation of response.
Time frame: From date of randomization up to 12 months
Overall Survival in the ITT population
Time from randomization until date of death from any cause.
Time frame: From date of randomization until death or study completion; assessed up to 36 months
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Hoag Gynecologic Oncology
Newport Beach, California, United States
RECRUITINGUCI Health Chao Family Comprehensive Cancer Center
Orange, California, United States
RECRUITINGAdventHealth Cancer Institute
Orlando, Florida, United States
RECRUITINGSarasota Memorial Research Institute
Sarasota, Florida, United States
RECRUITINGEmory University
Atlanta, Georgia, United States
RECRUITINGIndiana University Simon Comprehensive Cancer Center
Indianapolis, Indiana, United States
RECRUITING...and 21 more locations