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 same platinum-doublet 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. 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.
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 less than or equal to 24 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.
