Efficacy & Safety of Olvimulogene Nanivacirepvec & Platinum-doublet + Physician's Choice of Immune Checkpoint Inhibitor Compared to Docetaxel in NSCL Cancer (VIRO-25)

September 24, 2025 updated by: Genelux Corporation

A Randomized Phase 2 Study Assessing the Efficacy and Safety of Olvimulogene Nanivacirepvec Followed by Platinum-doublet Chemotherapy + Physician's Choice of Immune Checkpoint Inhibitor Compared With Docetaxel in Patients With NSCL Cancer After First Progression While on Front-line Immune Checkpoint Inhibitor-based Maintenance

This Phase 2, open-label, randomized study in non-small-cell lung cancer (NSCLC) is designed to evaluate the efficacy and safety of an intravenously delivered oncolytic vaccinia virus, Olvi-Vec, followed by platinum-doublet chemotherapy + Physician's Choice of Immune Checkpoint Inhibitor (ICI) vs. docetaxel for patients with advanced or metastatic NSCLC who have shown first disease progression (i.e., progressive disease not yet confirmed by further scan after initial scan showing progression) while on front-line treatment or maintenance ICI therapy after front-line treatment with platinum-doublet chemotherapy + ICI as standard of care.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Olvi-Vec (olvimulogene nanivacirepvec, aka GL-ONC1; laboratory name: GLV-1h68) is an oncolytic vaccinia virus-based immunotherapy that has been shown to have broad infectivity in a wide range of tumor types including non-small-cell lung cancer (NSCLC). In preclinical studies, Olvi-Vec was shown to infect and kill NSCLC cells and tumors in vitro and in vivo, respectively, and resolved and prevented formation of malignant effusion. This study is to test the hypothesis that the combination of Olvi-Vec followed by further platinum-based chemotherapy plus an ICI is particularly effective against established tumors by virus-mediated immune activation and re-sensitization of tumor cells to chemotherapy. Participants will have advanced or metastatic NSCLC (Stage III or Stage IV) squamous or nonsquamous disease without known targetable alterations in Epidermal Growth Factor Receptor (EGFR), Anaplastic Lymphoma Kinase (ALK) or Repressor of Silencing 1 (ROS1). Eligible patients will have first disease progression by radiological assessment (i) while on front-line platinum-doublet chemotherapy and ICI, or (ii) while receiving front-line maintenance ICI-based therapy after completion of front-line therapy, with at least 2 cycles and maximum of 6 cycles of platinum-doublet chemotherapy and ICI, regardless of Programmed death-ligand 1 (PD-L1) expression as the first treatment after being diagnosed. ICI includes anti-programmed death-1 (anti-PD-1) or anti-PD-L1 agents. Other classes of ICI [e.g., anti-cytotoxic T-lymphocyte antigen 4 (anti-CTLA-4), etc.] are excluded. Patients will be stratified based on length of time on ICI-based therapy from start date of the first dose, if ICI during front-line therapy, until date of first progression by radiological assessment is either less than or equal to 4 months or greater than 4 months. Patients enrolled in one of the initial 3 cohorts will receive either 3 or 4 days of Olvi-Vec followed by platinum-doublet chemotherapy + Physician's Choice of ICI. The randomization part of the study will start afterwards with the Olvi-Vec dose and schedule selected from one of the 3 cohorts for the Experimental Arm. The Active Comparator Arm (ACA) treatment includes docetaxel. Participants treated in the ACA who subsequently have documented disease progression may cross-over for treatment as per the Experimental Arm following determination of eligibility.

Study Type

Interventional

Enrollment (Estimated)

142

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arizona
      • Bullhead City, Arizona, United States, 86442
        • Recruiting
        • Pioneer Research Center, LLC
        • Contact:
        • Principal Investigator:
          • Hamdy Mohtaseb, MD
    • Florida
      • Clermont, Florida, United States, 34711
        • Recruiting
        • Clermont Oncology Center
        • Principal Investigator:
          • Gopal Kunta, MD
        • Contact:
      • Coral Springs, Florida, United States, 33065
        • Recruiting
        • Oncology & Hematology Associates of West Broward
        • Contact:
        • Principal Investigator:
          • Sumit Sawhney, MD
      • Fort Lauderdale, Florida, United States, 33316
      • Hialeah, Florida, United States, 33013
      • Miami, Florida, United States, 33136
        • Recruiting
        • University of Miami - Sylvester Comprehensive Cancer Center
        • Contact:
        • Principal Investigator:
          • Richa Dawar, MD
      • Miami, Florida, United States, 33155
      • Orange City, Florida, United States, 32763
        • Recruiting
        • Mid Florida Hematology and Oncology Center
        • Principal Investigator:
          • Santosh Nair, MD
        • Contact:
      • Plantation, Florida, United States, 33322
        • Recruiting
        • BRCR Medical Center, Inc.
        • Principal Investigator:
          • Harshad Amin, MD
        • Contact:
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • Recruiting
        • University of Maryland Medical Center Greenebaum Comprehensive Cancer Center
        • Contact:
        • Contact:
        • Principal Investigator:
          • Samuel Rosner, MD
    • Michigan
      • Dearborn, Michigan, United States, 48126
        • Recruiting
        • Michigan Hematology and Oncology Consultants
        • Principal Investigator:
          • Faisel Musa, MD
        • Contact:
      • Farmington Hills, Michigan, United States, 48336
    • Ohio
      • Canton, Ohio, United States, 44718
    • Texas
      • Austin, Texas, United States, 78745
        • Recruiting
        • Texas Oncology - Austin Central
        • Contact:
        • Principal Investigator:
          • James Uyeki, MD
      • Baytown, Texas, United States, 77521
    • Wisconsin
      • Sheboygan, Wisconsin, United States, 53081
        • Recruiting
        • Sheboygan Cancer & Blood Center
        • Contact:
        • Principal Investigator:
          • Steven M. Bettag, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Male or female 18 years or older.
  • ECOG (Eastern Cooperative Oncology Group) performance status of 0 or 1.
  • Have histologically or cytologically confirmed advanced or metastatic NSCLC.
  • Histologically confirmed Stage III or IV squamous or nonsquamous [American Joint Committee on Cancer (AJCC) 8th edition].
  • Received at least 2 cycles and maximum of 6 cycles of front-line platinum-based chemotherapy with ICI-based therapy, regardless of PD-L1 expression.
  • Reached first disease progression by radiological assessment while receiving front-line or maintenance ICI.
  • At least one measurable target tumor lesion anywhere except the brain per RECIST 1.1 by Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) scan.
  • Have adequate renal, hepatic, bone marrow function as well as adequate coagulation tests [International Normalized Ratio (INR)] and adequate immune function by lymphocyte count.
  • Women of child-bearing potential must have a negative serum pregnancy test prior to initiating study dosing.
  • Be willing and able to comply with scheduled visits, the treatment plan, imaging and laboratory tests.

Exclusion Criteria:

  • Active and untreated urinary tract infection, pneumonia, or other systemic infections.
  • Current symptomatic central nervous system (CNS) metastasis.
  • Any uncontrolled systemic disease, condition or comorbidity that, in the opinion of the Investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results.
  • Persistent toxicities [Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥ 3] caused by previous anticancer therapy; alopecia and vitiligo are excluded toxicities.
  • Required the use of additional immunosuppression other than corticosteroids for the management of an adverse event or have experienced recurrence of an adverse event if re-challenged, or currently require maintenance doses of >10 mg prednisone or equivalent per day.
  • Receiving concurrent antiviral agent active against vaccinia virus (e.g., cidofovir, vaccinia immunoglobulin, imatinib, tecovirimat, or other agents with known anti-vaccinia activities).
  • Underwent major surgery within 4 weeks, or have insufficient recovery from surgical-related trauma or wound healing, prior to the planned first dose of treatment in either Arm.
  • Have received prior virus-based gene therapy or therapy with cytolytic virus of any type.
  • Vaccination against smallpox or monkeypox within 1 year of study therapy.
  • Any non-oncology vaccine therapy used for prevention of infectious diseases, such as seasonal (influenza) vaccinations, corona virus disease (COVID) vaccination or other vaccines, within 2 weeks of the planned first dose of study drug.
  • Clinically significant skin disease as assessed by the Investigator (e.g., severe eczema, psoriasis, or any unresolved skin injury or ulcer).
  • Known hypersensitivity to carboplatin, cisplatin, paclitaxel or nab-paclitaxel, docetaxel, or any of the constituents of Olvi-Vec (i.e., gentamicin).
  • Had severe hypersensitivity (CTCAE Grade ≥ 3) to ICI and/or any of its excipients previously.
  • Dementia or altered mental status that would prohibit informed consent, and/or psychiatric illness/social situations that might interfere or limit compliance with study requirements.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Experimental Arm
Olvi-Vec will be administered at the dose and schedule selected from the single-arm run-in Olvi-Vec dose escalation cohorts followed 2 to 3 weeks later with platinum-doublet chemotherapy + Physician's Choice of ICI.
Biological: Olvimulogene nanivacirepvec
Olvi-Vec is an engineered oncolytic vaccinia virus
Other Names:
  • Olvi-Vec
  • GL-ONC
  • GLV-1h68
Drug: Platinum chemotherapy: carboplatin or cisplatin
Administered according to local practice.
Other Names:
  • Brand of drug is based on institutional procurement
Drug: Non-platinum chemotherapy: paclitaxel or nab-paclitaxel for squamous cell NSCLC or pemetrexed for nonsquamous cell NSCLC
Administered according to local practice.
Other Names:
  • Brand of drug is based on institutional procurement
Drug: Physician's Choice of Immune Checkpoint Inhibitor: pembrolizumab, nivolumab, cemiplimab, atezolizumab, durvalumab
Administered according to local practice.
Other Names:
  • Brand of drug is based on institutional procurement
Active Comparator: Active Comparator Arm
Docetaxel starts in Week 0 and continues until disease progression is assessed by the BICR.
Drug: Docetaxel
Administered according to local practice.
Other Names:
  • Brand of drug is based on institutional procurement
Other: Active Comparator Arm Cross-over
Patients randomized into the Active Comparator can cross-over to receive the same treatment as given in the Experimental Arm following determination of (1) disease progression by BICR after receiving docetaxel treatment and (2) confirming eligibility.
Biological: Olvimulogene nanivacirepvec
Olvi-Vec is an engineered oncolytic vaccinia virus
Other Names:
  • Olvi-Vec
  • GL-ONC
  • GLV-1h68
Drug: Platinum chemotherapy: carboplatin or cisplatin
Administered according to local practice.
Other Names:
  • Brand of drug is based on institutional procurement
Drug: Non-platinum chemotherapy: paclitaxel or nab-paclitaxel for squamous cell NSCLC or pemetrexed for nonsquamous cell NSCLC
Administered according to local practice.
Other Names:
  • Brand of drug is based on institutional procurement
Drug: Physician's Choice of Immune Checkpoint Inhibitor: pembrolizumab, nivolumab, cemiplimab, atezolizumab, durvalumab
Administered according to local practice.
Other Names:
  • Brand of drug is based on institutional procurement
Drug: Docetaxel
Administered according to local practice.
Other Names:
  • Brand of drug is based on institutional procurement
Experimental: Single-arm run-in Olvi-Vec dose escalation Cohorts

Cohort 1: Olvi-Vec administered over 3 consecutive days at 0.5,0.5,0.5 x 10e9 pfu followed 2 to 3 weeks later with platinum-doublet chemotherapy + Physician's Choice of ICI.

Cohort 2: Olvi-Vec administered over 3 consecutive days at 1,1,1 x 10e9 pfu followed 2 to 3 weeks later with platinum-doublet chemotherapy + Physician's Choice of ICI.

Cohort 3: Olvi-Vec administered over 4 consecutive days at 1,2,3 x 10e9 pfu followed 2 to 3 weeks later with platinum-doublet chemotherapy + Physician's Choice of ICI.
Biological: Olvimulogene nanivacirepvec
Olvi-Vec is an engineered oncolytic vaccinia virus
Other Names:
  • Olvi-Vec
  • GL-ONC
  • GLV-1h68
Drug: Platinum chemotherapy: carboplatin or cisplatin
Administered according to local practice.
Other Names:
  • Brand of drug is based on institutional procurement
Drug: Non-platinum chemotherapy: paclitaxel or nab-paclitaxel for squamous cell NSCLC or pemetrexed for nonsquamous cell NSCLC
Administered according to local practice.
Other Names:
  • Brand of drug is based on institutional procurement
Drug: Physician's Choice of Immune Checkpoint Inhibitor: pembrolizumab, nivolumab, cemiplimab, atezolizumab, durvalumab
Administered according to local practice.
Other Names:
  • Brand of drug is based on institutional procurement

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free Survival per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 by Blinded Independent Central Review (BICR)
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.
From date of randomization up to 12 months.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Median Overall Survival
Time Frame: From date of randomization up to 36 months.
Time from randomization until death or study completion; assessed up to 36 months.
From date of randomization up to 36 months.
Six-month Progression-free Survival Rate
Time Frame: From date of randomization up to 6 months.
Proportion of patients who remained alive and progression-free at 6 months.
From date of randomization up to 6 months.
Incidence of Treatment-emergent Adverse Events
Time Frame: Assessed up to 36 months.
From date of first study treatment until death or study completion.
Assessed up to 36 months.
Duration of Response by RECIST 1.1
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.
From date of randomization up to 12 months.
Objective Response Rate (ORR) by RECIST 1.1
Time Frame: From date of randomization up to 12 months.
Ratio of the sum of complete responses (CR) & partial responses (PR) divided by the number of participants from start of treatment to confirmation of response.
From date of randomization up to 12 months.
Disease Control Rate (DCR)
Time Frame: From date of randomization up to 12 months.
Percentage of patients who have achieved complete response, partial response or stable disease out of the total number of patients evaluated in a therapeutic intervention in clinical trials: DCR = [CR + PR + SD (stable disease)]/total # of patients evaluated by RECIST 1.1.
From date of randomization up to 12 months.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Genelux Corporation

Collaborators

Newsoara Biopharma Co., Ltd.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 26, 2024

Primary Completion (Estimated)

February 1, 2027

Study Completion (Estimated)

July 1, 2029

Study Registration Dates

First Submitted

June 11, 2024

First Submitted That Met QC Criteria

June 13, 2024

First Posted (Actual)

June 18, 2024

Study Record Updates

Last Update Posted (Estimated)

September 26, 2025

Last Update Submitted That Met QC Criteria

September 24, 2025

Last Verified

September 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Olvi-Vec-NSCLC-025

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Non-small Cell Lung Cancer Stage III

Clinical Trials on Olvimulogene nanivacirepvec

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in South Africa

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe