Clinical trial NCT05281471: 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)
Official title: A Randomized Phase 3 Study Assessing the Efficacy and Safety of Olvi-Vec Followed by Platinum-doublet Chemotherapy and Bevacizumab Compared With Physician's Choice of Chemotherapy and Bevacizumab in Women With Platinum-Resistant/Refractory Ovarian Cancer (PRROC) (OnPrime, GOG-3076)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Platinum-resistant Ovarian Cancer
Platinum-refractory Ovarian Cancer
Fallopian Tube Cancer
Primary Peritoneal Cancer
High-grade Serous Ovarian Cancer
Endometrioid Ovarian Cancer
Ovarian Clear Cell Carcinoma
Keywords: olvimulogene nanivacirepvec
GL-ONC1
GLV-1h68
oncolytic virus
virotherapy
viral therapy
immunotherapy
immunochemotherapy
combination therapy
vaccinia virus
ovarian cancer
fallopian tube cancer
primary peritoneal cancer
platinum resistant
platinum refractory
recurrent ovarian cancer
platinum resensitization
chemoresistance
heavily pre-treated
immune activation
reversal of platinum resistance or refractoriness
resensitize
Lead sponsor: Genelux Corporation
Sponsor class: INDUSTRY
Collaborators: name: GOG Foundation
First posted: 2022-03-16
Enrollment: 186
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomization (2:1) is either into the Experimental Arm which is Olvi-Vec followed by platinum-doublet chemotherapy and bevacizumab or into the Active Comparator Arm which is Physician's Choice of chemotherapy and bevacizumab.
Primary purpose: TREATMENT

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.

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.
* 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.

Primary outcomes:
measure: 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)
timeFrame: From date of randomization up to 12 months
Secondary outcomes:
measure: Incidence of Treatment-emergent Adverse Events in the ITT population
timeFrame: From date of first study treatment until death or study completion; assessed up to 36 months
measure: Duration of Response (DOR) by RECIST 1.1 in the ITT population
timeFrame: From date of randomization up to 12 months
measure: PFS by RECIST 1.1 in the modified ITT (mITT) population (participants who received at least 1 dose of treatment in either Arm)
timeFrame: From date of randomization up to 12 months
measure: PFS by iRECIST in the ITT population
timeFrame: From date of randomization up to 12 months
measure: Overall Response Rate (ORR) by RECIST 1.1 in the ITT population
timeFrame: From date of randomization up to 12 months
measure: Overall Survival in the ITT population
timeFrame: From date of randomization until death or study completion; assessed up to 36 months
Other outcomes:
Locations:
city: Mobile
country: United States
facility: The University of South Alabama, Mitchell Cancer Institute
state: Alabama
city: Tucson
country: United States
facility: University of Arizona Cancer Center
state: Arizona
city: Duarte
country: United States
facility: City of Hope
state: California
city: La Jolla
country: United States
facility: UC San Diego Health - Moores Cancer Center
state: California
city: Newport Beach
country: United States
facility: Hoag Gynecologic Oncology
state: California
city: Orange
country: United States
facility: UCI Health Chao Family Comprehensive Cancer Center
state: California
city: Orlando
country: United States
facility: AdventHealth Cancer Institute
state: Florida
city: Saint Petersburg
country: United States
facility: Women's Cancer Associates with Women's Care Florida
state: Florida
city: Sarasota
country: United States
facility: Sarasota Memorial Research Institute
state: Florida
city: Tampa
country: United States
facility: Tampa General Hospital/University of South Florida
state: Florida
city: Indianapolis
country: United States
facility: Indiana University Simon Comprehensive Cancer Center
state: Indiana
city: Silver Spring
country: United States
facility: Holy Cross Hospital
state: Maryland
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Saint Louis
country: United States
facility: Mercy Hospital St. Louis
state: Missouri
city: Las Vegas
country: United States
facility: Women's Cancer Center of Nevada
state: Nevada
city: Reno
country: United States
facility: Center of Hope
state: Nevada
city: Stony Brook
country: United States
facility: Stony Brook Cancer Center
state: New York
city: Charlotte
country: United States
facility: Levine Cancer Institute
state: North Carolina
city: Greenville
country: United States
facility: East Carolina University
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: OhioHealth Research Institute
state: Ohio
city: Kettering
country: United States
facility: Kettering Health
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma University Health Stephenson Cancer Center
state: Oklahoma
city: Pittsburgh
country: United States
facility: AHN West Penn Hospital
state: Pennsylvania
city: Charleston
country: United States
facility: Hollings Cancer Center
state: South Carolina
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Houston
country: United States
facility: University of Texas Science Center at Houston, McGovern Medical School
state: Texas
city: Spokane
country: United States
facility: Providence Sacred Heart Medical Center & Children's Hospital
state: Washington
Study officials:
affiliation: AdventHealth Cancer Institute
name: Robert W. Holloway, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mori KM, Giuliano PD, Lopez KL, King MM, Bohart R, Goldstein BH. Pronounced clinical response following the oncolytic vaccinia virus GL-ONC1 and chemotherapy in a heavily pretreated ovarian cancer patient. Anticancer Drugs. 2019 Nov;30(10):1064-1066. doi: 10.1097/CAD.0000000000000836.
citation: Manyam M, Stephens AJ, Kennard JA, LeBlanc J, Ahmad S, Kendrick JE, Holloway RW. A phase 1b study of intraperitoneal oncolytic viral immunotherapy in platinum-resistant or refractory ovarian cancer. Gynecol Oncol. 2021 Dec;163(3):481-489. doi: 10.1016/j.ygyno.2021.10.069. Epub 2021 Oct 20.
citation: Holloway RW, Mendivil AA, Kendrick JE, Abaid LN, Brown JV, Fitzsimmons CK, Kennard JA, King M, LeBlanc J, Lopez K, Manyam M, McKenzie ND, Mori KM, Stephens AJ, Sarfraz A. 2020 International Gynecologic Cancer Society, Oral Plenary Session presentation of VIRO-15 Phase 2 Trial Data, Robert Holloway, AdventHealth Cancer Institute, Orlando, FL. International Journal of Gynecologic Cancer 2020;30:A9-A10
citation: Holloway RW, Mendivil AA, Kendrick JE, Abaid LN, Brown JV, LeBlanc J, McKenzie ND, Mori KM, Ahmad S. Clinical Activity of Olvimulogene Nanivacirepvec-Primed Immunochemotherapy in Heavily Pretreated Patients With Platinum-Resistant or Platinum-Refractory Ovarian Cancer: The Nonrandomized Phase 2 VIRO-15 Clinical Trial. JAMA Oncol. 2023 Jul 1;9(7):903-908. doi: 10.1001/jamaoncol.2023.1007.