Brief Title
Efficacy & Safety of Olvi-Vec and Platinum-doublet + Bevacizumab Compared to Platinum-doublet + Bevacizumab in Platinum-Resistant/Refractory Ovarian Cancer
Official Title
A Randomized Phase 3 Study Assessing the Efficacy and Safety of Olvi-Vec Followed by Platinum-doublet Chemotherapy and Bevacizumab Compared With Platinum-doublet Chemotherapy and Bevacizumab in Women With Platinum-Resistant/Refractory Ovarian Cancer
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 platinum-doublet chemotherapy and bevacizumab in
women diagnosed with platinum-resistant/refractory ovarian cancer (includes fallopian tube
cancer and primary peritoneal cancer).
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 intraperitoneal infusion of Olvi-Vec through a catheter in
addition to platinum-doublet chemotherapy and bevacizumab. Treatment in the Active Comparator
Arm allows the same platinum-doublet chemotherapy and bevacizumab as the Experimental Arm.
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. 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 Phase
Phase 3
Study Type
Interventional
Primary Outcome
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)
Secondary Outcome
Incidence of Treatment-emergent Adverse Events in the ITT population
Condition
Platinum-resistant Ovarian Cancer
Intervention
olvimulogene nanivacirepvec
Study Arms / Comparison Groups
Olvi-Vec + Platinum-doublet & bevacizumab
Description: 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
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Biological
Estimated Enrollment
186
Start Date
August 2022
Completion Date
October 2026
Primary Completion Date
August 2024
Eligibility Criteria
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.
- Time from Last Platinum of 3-15 months since the last dose of platinum in the most
recent platinum-based line of therapy (excluding using platinum as a radiosensitizer)
until consent into this trial.
- 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.
Gender
Female
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Robert W Holloway, MD, FACOG, FACS, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT05281471
Organization ID
Olvi-Vec-022
Secondary IDs
GOG-3076
Responsible Party
Sponsor
Study Sponsor
Genelux Corporation
Collaborators
GOG Foundation
Study Sponsor
Robert W Holloway, MD, FACOG, FACS, Principal Investigator, AdventHealth Cancer Institute, Orlando, FL
Verification Date
July 2022