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

• ClinicalTrials.gov Identifier: NCT05281471
• Recruitment Status: Recruiting
• First Posted: March 16, 2022
• Last Update Posted: April 6, 2023
• Sponsor: Genelux Corporation
• Collaborator: GOG Foundation
• Information provided by (Responsible Party): Genelux Corporation

Tracking Information

• First Submitted Date: March 7, 2022
• First Posted Date: March 16, 2022
• Last Update Posted Date: April 6, 2023
• Actual Study Start Date: August 31, 2022
• Estimated Primary Completion Date: August 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 7, 2022)

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) [ Time Frame: From date of randomization up to 12 months ]

To assess progression-free survival from time of randomization until first documented disease progression based on radiological assessment or death from any cause.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: March 7, 2022)

• Incidence of Treatment-emergent Adverse Events in the ITT population [ Time Frame: From date of first study treatment until death or study completion; assessed up to 36 months ]
  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.
• Duration of Response (DOR) by RECIST 1.1 in the ITT population [ Time Frame: From date of randomization up to 12 months ]
  Time from date of first response until the first date of progressive disease based on radiological assessment.
• PFS by RECIST 1.1 in the modified ITT (mITT) population (participants who received at least 1 dose of treatment in either Arm) [ Time Frame: From date of randomization up to 12 months ]
  Time from randomization to first documented disease progression based on radiological assessment or death from any cause.
• PFS by iRECIST in the ITT population [ Time Frame: From date of randomization up to 12 months ]
  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.
• Overall Response Rate (ORR) by RECIST 1.1 in the ITT population [ Time Frame: From date of randomization up to 12 months ]
  Ratio of the sum of CR & PR divided by the number of ITT participants from start of treatment to confirmation of response.
• Overall Survival in the ITT population [ Time Frame: From date of randomization until death or study completion; assessed up to 36 months ]
  Time from randomization until date of death from any cause.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Efficacy & Safety of Olvi-Vec and Platinum-doublet + Bevacizumab Compared to Platinum-doublet + Bevacizumab in Platinum-Resistant/Refractory Ovarian Cancer (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 Platinum-doublet Chemotherapy and Bevacizumab in Women With Platinum-Resistant/Refractory Ovarian Cancer (OnPrime, GOG-3076)
• 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 Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
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 platinum-doublet chemotherapy and bevacizumab.

Masking: None (Open Label)
Primary Purpose: Treatment

Condition

• 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

Intervention

• Biological: olvimulogene nanivacirepvec
  Olvi-Vec is an engineered oncolytic vaccinia virus
  Other Name: GL-ONC1 and GLV-1h68
• Drug: Platinum chemotherapy: carboplatin (preferred) or cisplatin
  Administered according to local practice
• Drug: Non-platinum chemotherapy: Physician's Choice of gemcitabine, taxane (paclitaxel, docetaxel or nab-paclitaxel) or pegylated liposomal doxorubicin
  Administered according to local practice
• Drug: Bevacizumab (or biosimilar)
  Administered according to local practice

Study Arms

• Experimental: Olvi-Vec + Platinum-doublet & bevacizumab

  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

  Interventions:

  • Biological: olvimulogene nanivacirepvec
  • Drug: Platinum chemotherapy: carboplatin (preferred) or cisplatin
  • Drug: Non-platinum chemotherapy: Physician's Choice of gemcitabine, taxane (paclitaxel, docetaxel or nab-paclitaxel) or pegylated liposomal doxorubicin
  • Drug: Bevacizumab (or biosimilar)
• Active Comparator: Platinum-doublet & bevacizumab
  Platinum-doublet & bevacizumab (or biosimilar) administered beginning in Week 0
  Interventions:

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

Publications *

• 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.
• 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. Erratum In: Gynecol Oncol. 2022 May;165(2):401.
• 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

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: March 7, 2022): 186
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: October 2026
• Estimated Primary Completion Date: August 2024 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05281471
• Other Study ID Numbers: Olvi-Vec-022; GOG-3076 ( Other Identifier: GOG Foundation )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Genelux Corporation
• Original Responsible Party: Same as current
• Current Study Sponsor: Genelux Corporation
• Original Study Sponsor: Same as current
• Collaborators: GOG Foundation

Investigators

• Principal Investigator: Robert W Holloway, MD, FACOG, FACS; OnPrime Study

• PRS Account: Genelux Corporation
• Verification Date: April 2023