Efficacy & Safety of Olvi-Vec and Platinum-doublet + Bevacizumab Compared to Physician's Choice of Chemotherapy and Bevacizumab in Platinum-Resistant/Refractory Ovarian Cancer (OnPrime, GOG-3076)

Fallopian Tube Cancer Clinical Trial

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 (OnPrime, GOG-3076)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05281471
• Other study ID #: Olvi-Vec-022
• Secondary ID: GOG-3076
• Status: Recruiting
• Phase: Phase 3
• Start date: August 31, 2022
• Est. completion date: October 2026

Study information

• Verified date: May 2024
• Source: Genelux Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Recruiting
• Enrollment: 186
• Est. completion date: October 2026
• Est. primary completion date: August 2025
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Ovarian Epithelial
• Fallopian Tube Cancer
• Fallopian Tube Neoplasms
• High-grade Serous Ovarian Cancer
• Ovarian Clear Cell Carcinoma
• Ovarian Neoplasms
• Platinum-resistant Ovarian Cancer
• Primary Peritoneal Cancer

Intervention

Biological:
• olvimulogene nanivacirepvec
Olvi-Vec is an engineered oncolytic vaccinia virus

Drug:
• Platinum chemotherapy: carboplatin (preferred) or cisplatin
Administered according to local practice
• Non-platinum chemotherapy: Physician's Choice of gemcitabine, taxane (paclitaxel, docetaxel or nab-paclitaxel) or pegylated liposomal doxorubicin
Administered according to local practice
• Bevacizumab (or biosimilar)
Administered according to local practice

Locations

Country	Name	City	State
United States	Hollings Cancer Center	Charleston	South Carolina
United States	Levine Cancer Institute	Charlotte	North Carolina
United States	Chattanooga's Program in Women's Oncology	Chattanooga	Tennessee
United States	Cleveland Clinic	Cleveland	Ohio
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	City of Hope	Duarte	California
United States	Indiana University Simon Comprehensive Cancer Center	Indianapolis	Indiana
United States	Kettering Health	Kettering	Ohio
United States	UC San Diego Health - Moores Cancer Center	La Jolla	California
United States	The University of South Alabama, Mitchell Cancer Institute	Mobile	Alabama
United States	Hoag Gynecologic Oncology	Newport Beach	California
United States	Oklahoma University Health Stephenson Cancer Center	Oklahoma City	Oklahoma
United States	UCI Health Chao Family Comprehensive Cancer Center	Orange	California
United States	AdventHealth Cancer Institute	Orlando	Florida
United States	AHN West Penn Hospital	Pittsburgh	Pennsylvania
United States	Center of Hope	Reno	Nevada
United States	Mercy Hospital St. Louis	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Holy Cross Hospital	Silver Spring	Maryland
United States	Providence Sacred Heart Medical Center & Children's Hospital	Spokane	Washington
United States	Tampa General Hospital/University of South Florida	Tampa	Florida
United States	Women's Cancer Associates with Women's Care Florida	Tampa	Florida
United States	University of Arizona Cancer Center	Tucson	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
Genelux Corporation	GOG Foundation

Country where clinical trial is conducted

United States, 

References & Publications (4)

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

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 O — View 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.y — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	From date of randomization up to 12 months
Secondary	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.	From date of first study treatment until death or study completion; assessed up to 36 months
Secondary	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.	From date of randomization up to 12 months
Secondary	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.	From date of randomization up to 12 months
Secondary	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.	From date of randomization up to 12 months
Secondary	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.	From date of randomization up to 12 months
Secondary	Overall Survival in the ITT population	Time from randomization until date of death from any cause.	From date of randomization until death or study completion; assessed up to 36 months

External Links

•   Genelux Corporation's clinical publications
•   Genelux Corporation's preclinical publications
•   Genelux Corporation's Sponsor website
•   IGCS 2020 Oral Plenary: Dr. Robert W. Holloway - Oncolytic vaccinia (Olvi-Vec) primed immunochemotherapy in platinum-resistant/refractory ovarian cancer
•   The GOG Foundation's Partner website