NCT05281471

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.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
186

participants targeted

Target at P25-P50 for phase_3

Timeline
4mo left

Started Aug 2022

Typical duration for phase_3

Geographic Reach
1 country

31 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress93%
Aug 2022Oct 2026

First Submitted

Initial submission to the registry

March 7, 2022

Completed
9 days until next milestone

First Posted

Study publicly available on registry

March 16, 2022

Completed
6 months until next milestone

Study Start

First participant enrolled

August 31, 2022

Completed
3.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2026

Completed
4 months until next milestone

Study Completion

Last participant's last visit for all outcomes

October 1, 2026

Expected
Last Updated

March 18, 2026

Status Verified

March 1, 2026

Enrollment Period

3.8 years

First QC Date

March 7, 2022

Last Update Submit

March 16, 2026

Conditions

Keywords

olvimulogene nanivacirepvecGL-ONC1GLV-1h68oncolytic virusvirotherapyviral therapyimmunotherapyimmunochemotherapycombination therapyvaccinia virusovarian cancerfallopian tube cancerprimary peritoneal cancerplatinum resistantplatinum refractoryrecurrent ovarian cancerplatinum resensitizationchemoresistanceheavily pre-treatedimmune activationreversal of platinum resistance or refractorinessresensitize

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (6)

  • Incidence of Treatment-emergent Adverse Events in the ITT population

    From date of first study treatment until death or study completion; assessed up to 36 months

  • Duration of Response (DOR) by RECIST 1.1 in the ITT population

    From date of randomization up to 12 months

  • PFS by RECIST 1.1 in the modified ITT (mITT) population (participants who received at least 1 dose of treatment in either Arm)

    From date of randomization up to 12 months

  • PFS by iRECIST in the ITT population

    From date of randomization up to 12 months

  • Overall Response Rate (ORR) by RECIST 1.1 in the ITT population

    From date of randomization up to 12 months

  • +1 more secondary outcomes

Study Arms (2)

Olvi-Vec + Platinum-doublet & bevacizumab

EXPERIMENTAL

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

Biological: olvimulogene nanivacirepvecDrug: Platinum chemotherapy: carboplatin (preferred) or cisplatinDrug: Non-platinum chemotherapy: Physician's Choice of gemcitabine, taxane (paclitaxel, docetaxel or nab-paclitaxel) or pegylated liposomal doxorubicinDrug: Bevacizumab (or biosimilar)

Physician's Choice of Chemotherapy & bevacizumab

ACTIVE COMPARATOR

Physician's Choice of chemotherapy \& bevacizumab (or biosimilar) administered beginning in Week 0. Physician's Choice of chemotherapy includes either a single agent non-platinum chemotherapy, or as platinum chemotherapy is allowed as an option, a platinum-doublet (i.e., platinum agent combined with a non-platinum agent).

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

Interventions

Olvi-Vec is an engineered oncolytic vaccinia virus

Also known as: GL-ONC1 and GLV-1h68
Olvi-Vec + Platinum-doublet & bevacizumab

Administered according to local practice

Olvi-Vec + Platinum-doublet & bevacizumabPhysician's Choice of Chemotherapy & bevacizumab

Administered according to local practice

Olvi-Vec + Platinum-doublet & bevacizumabPhysician's Choice of Chemotherapy & bevacizumab

Administered according to local practice

Olvi-Vec + Platinum-doublet & bevacizumabPhysician's Choice of Chemotherapy & bevacizumab

Eligibility Criteria

Age18 Years+
Sexfemale
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.
  • +6 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (31)

The University of South Alabama, Mitchell Cancer Institute

Mobile, Alabama, 36604, United States

RECRUITING

University of Arizona Cancer Center

Tucson, Arizona, 85719, United States

RECRUITING

City of Hope

Duarte, California, 91010, United States

RECRUITING

UC San Diego Health - Moores Cancer Center

La Jolla, California, 92093, United States

RECRUITING

Hoag Gynecologic Oncology

Newport Beach, California, 92663, United States

RECRUITING

UCI Health Chao Family Comprehensive Cancer Center

Orange, California, 92868, United States

RECRUITING

AdventHealth Cancer Institute

Orlando, Florida, 32804, United States

RECRUITING

Sarasota Memorial Research Institute

Sarasota, Florida, 34239, United States

RECRUITING

Emory University

Atlanta, Georgia, 30322, United States

RECRUITING

Indiana University Simon Comprehensive Cancer Center

Indianapolis, Indiana, 46202, United States

RECRUITING

Holy Cross Hospital

Silver Spring, Maryland, 20910, United States

RECRUITING

University of Michigan

Ann Arbor, Michigan, 48109, United States

RECRUITING

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

RECRUITING

Washington University School of Medicine

St Louis, Missouri, 63110, United States

RECRUITING

Mercy Hospital St. Louis

St Louis, Missouri, 63141, United States

RECRUITING

Women's Cancer Center of Nevada

Las Vegas, Nevada, 89106, United States

RECRUITING

Center of Hope

Reno, Nevada, 89511, United States

RECRUITING

Stony Brook Cancer Center

Stony Brook, New York, 11794, United States

RECRUITING

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

RECRUITING

East Carolina University

Greenville, North Carolina, 27834, United States

RECRUITING

Cleveland Clinic

Cleveland, Ohio, 44195, United States

RECRUITING

OhioHealth Research Institute

Columbus, Ohio, 43214, United States

RECRUITING

Kettering Health

Kettering, Ohio, 45429, United States

RECRUITING

ProMedica Flower Hospital

Sylvania, Ohio, 43560, United States

RECRUITING

Oklahoma University Health Stephenson Cancer Center

Oklahoma City, Oklahoma, 73104, United States

RECRUITING

AHN West Penn Hospital

Pittsburgh, Pennsylvania, 15224, United States

RECRUITING

Hollings Cancer Center

Charleston, South Carolina, 29425, United States

RECRUITING

Erlanger Health, Inc.

Chattanooga, Tennessee, 37403, United States

RECRUITING

Baylor College of Medicine

Houston, Texas, 77030, United States

RECRUITING

University of Texas Science Center at Houston, McGovern Medical School

Houston, Texas, 77030, United States

RECRUITING

Providence Sacred Heart Medical Center & Children's Hospital

Spokane, Washington, 99204, United States

RECRUITING

Related Publications (5)

  • 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.

    PMID: 31567308BACKGROUND
  • 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.

  • 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

    RESULT
  • 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.

  • Holloway RW, Thaker P, Mendivil AA, Ahmad S, Al-Niaimi AN, Barter J, Beck T, Chambers SK, Coleman RL, Crafton SM, Crane E, Ramez E, Ghamande S, Graybill W, Herzog T, Indermaur MD, John VS, Landrum L, Lim PC, Lucci JA, McHale M, Monk BJ, Moore KN, Morris R, O'Malley DM, Reid TJ, Richardson D, Rose PG, Scalici JM, Silasi DA, Tewari K, Wang EW. A phase III, multicenter, randomized study of olvimulogene nanivacirepvec followed by platinum-doublet chemotherapy and bevacizumab compared with platinum-doublet chemotherapy and bevacizumab in women with platinum-resistant/refractory ovarian cancer. Int J Gynecol Cancer. 2023 Sep 4;33(9):1458-1463. doi: 10.1136/ijgc-2023-004812.

Related Links

MeSH Terms

Conditions

Fallopian Tube NeoplasmsVacciniaOvarian Neoplasms

Interventions

CisplatintaxanePaclitaxelDocetaxel130-nm albumin-bound paclitaxelliposomal doxorubicinBevacizumabBiosimilar Pharmaceuticals

Condition Hierarchy (Ancestors)

Genital Neoplasms, FemaleUrogenital NeoplasmsNeoplasms by SiteNeoplasmsFallopian Tube DiseasesAdnexal DiseasesGenital Diseases, FemaleFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesGenital DiseasesPoxviridae InfectionsDNA Virus InfectionsVirus DiseasesInfectionsEndocrine Gland NeoplasmsOvarian DiseasesEndocrine System DiseasesGonadal Disorders

Intervention Hierarchy (Ancestors)

Chlorine CompoundsInorganic ChemicalsNitrogen CompoundsPlatinum CompoundsTaxoidsCyclodecanesCycloparaffinsHydrocarbons, AlicyclicHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsDiterpenesTerpenesAntibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsBiological ProductsComplex Mixtures

Study Officials

  • Robert W. Holloway, MD

    AdventHealth Cancer Institute

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: 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.
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 7, 2022

First Posted

March 16, 2022

Study Start

August 31, 2022

Primary Completion

June 1, 2026

Study Completion (Estimated)

October 1, 2026

Last Updated

March 18, 2026

Record last verified: 2026-03

Data Sharing

IPD Sharing
Will not share

Locations