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

NCT ID: NCT06463665

Last Updated: 2025-09-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

142 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-09-26

Study Completion Date

2029-07-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Advanced Non-squamous Non-small-cell Lung Cancer Advanced Squamous Non-Small Cell Lung Carcinoma Metastatic Non-squamous Non Small Cell Lung Cancer Metastatic Squamous Non-Small Cell Lung Carcinoma Non-small Cell Lung Cancer Non-small Cell Lung Cancer Stage III Non-small Cell Lung Cancer Stage IV Non-small Cell Lung Cancer Recurrent

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Following selection of the dose and schedule from the three safety run-in cohorts, randomization is (1:1) either into the Experimental Arm (EA) which is Olvi-Vec with platinum-doublet + Physician's Choice of ICI and then ICI-based maintenance or in the Active Comparator Arm (ACA) which includes treatment with docetaxel. ACA patients with documented disease progression \[i.e., assessed by Blinded Independent Central Review (BICR)\] who are eligible may crossover to receive the same treatment as per the Experimental Arm.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Olvimulogene nanivacirepvec

Intervention Type BIOLOGICAL

Olvi-Vec is an engineered oncolytic vaccinia virus

Platinum chemotherapy: carboplatin or cisplatin

Intervention Type DRUG

Administered according to local practice.

Non-platinum chemotherapy: paclitaxel or nab-paclitaxel for squamous cell NSCLC or pemetrexed for nonsquamous cell NSCLC

Intervention Type DRUG

Administered according to local practice.

Physician's Choice of Immune Checkpoint Inhibitor: pembrolizumab, nivolumab, cemiplimab, atezolizumab, durvalumab

Intervention Type DRUG

Administered according to local practice.

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.

Group Type EXPERIMENTAL

Olvimulogene nanivacirepvec

Intervention Type BIOLOGICAL

Olvi-Vec is an engineered oncolytic vaccinia virus

Platinum chemotherapy: carboplatin or cisplatin

Intervention Type DRUG

Administered according to local practice.

Non-platinum chemotherapy: paclitaxel or nab-paclitaxel for squamous cell NSCLC or pemetrexed for nonsquamous cell NSCLC

Intervention Type DRUG

Administered according to local practice.

Physician's Choice of Immune Checkpoint Inhibitor: pembrolizumab, nivolumab, cemiplimab, atezolizumab, durvalumab

Intervention Type DRUG

Administered according to local practice.

Active Comparator Arm

Docetaxel starts in Week 0 and continues until disease progression is assessed by the BICR.

Group Type ACTIVE_COMPARATOR

Docetaxel

Intervention Type DRUG

Administered according to local practice.

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.

Group Type OTHER

Olvimulogene nanivacirepvec

Intervention Type BIOLOGICAL

Olvi-Vec is an engineered oncolytic vaccinia virus

Platinum chemotherapy: carboplatin or cisplatin

Intervention Type DRUG

Administered according to local practice.

Non-platinum chemotherapy: paclitaxel or nab-paclitaxel for squamous cell NSCLC or pemetrexed for nonsquamous cell NSCLC

Intervention Type DRUG

Administered according to local practice.

Physician's Choice of Immune Checkpoint Inhibitor: pembrolizumab, nivolumab, cemiplimab, atezolizumab, durvalumab

Intervention Type DRUG

Administered according to local practice.

Docetaxel

Intervention Type DRUG

Administered according to local practice.

Interventions

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Olvimulogene nanivacirepvec

Olvi-Vec is an engineered oncolytic vaccinia virus

Intervention Type BIOLOGICAL

Platinum chemotherapy: carboplatin or cisplatin

Administered according to local practice.

Intervention Type DRUG

Non-platinum chemotherapy: paclitaxel or nab-paclitaxel for squamous cell NSCLC or pemetrexed for nonsquamous cell NSCLC

Administered according to local practice.

Intervention Type DRUG

Physician's Choice of Immune Checkpoint Inhibitor: pembrolizumab, nivolumab, cemiplimab, atezolizumab, durvalumab

Administered according to local practice.

Intervention Type DRUG

Docetaxel

Administered according to local practice.

Intervention Type DRUG

Other Intervention Names

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Olvi-Vec GL-ONC GLV-1h68 Brand of drug is based on institutional procurement Brand of drug is based on institutional procurement Brand of drug is based on institutional procurement Brand of drug is based on institutional procurement

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Newsoara Biopharma Co., Ltd.

INDUSTRY

Sponsor Role collaborator

Genelux Corporation

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Pioneer Research Center, LLC

Bullhead City, Arizona, United States

Site Status RECRUITING

Clermont Oncology Center

Clermont, Florida, United States

Site Status RECRUITING

Oncology & Hematology Associates of West Broward

Coral Springs, Florida, United States

Site Status RECRUITING

Helios Clinical Research

Fort Lauderdale, Florida, United States

Site Status RECRUITING

Bioresearch Partner

Hialeah, Florida, United States

Site Status RECRUITING

University of Miami - Sylvester Comprehensive Cancer Center

Miami, Florida, United States

Site Status RECRUITING

Bioresearch Partner

Miami, Florida, United States

Site Status RECRUITING

Mid Florida Hematology and Oncology Center

Orange City, Florida, United States

Site Status RECRUITING

BRCR Medical Center, Inc.

Plantation, Florida, United States

Site Status RECRUITING

University of Maryland Medical Center Greenebaum Comprehensive Cancer Center

Baltimore, Maryland, United States

Site Status RECRUITING

Michigan Hematology and Oncology Consultants

Dearborn, Michigan, United States

Site Status RECRUITING

Oakland Medical Group

Farmington Hills, Michigan, United States

Site Status RECRUITING

Gabrail Cancer and Research Center

Canton, Ohio, United States

Site Status RECRUITING

Texas Oncology - Austin Central

Austin, Texas, United States

Site Status RECRUITING

World Research Link

Baytown, Texas, United States

Site Status RECRUITING

Sheboygan Cancer & Blood Center

Sheboygan, Wisconsin, United States

Site Status RECRUITING

Countries

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United States

Facility Contacts

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Hamdy Mohtaseb, MD

Role: primary

928-216-4560

Kiran Penta

Role: primary

386-538-3169

Sumit Sawhney, MD

Role: primary

954-726-0035

Kylee Charlemagne

Role: primary

645-225-9003

Jenrrys Mejias

Role: primary

833-489-4968

Jonathan Matias

Role: backup

833-489-4968

Richa Dawar, MD

Role: primary

954-461-2107

Handy Del Sol Bello

Role: primary

833-489-4968

Marianna Wefer

Role: backup

833-489-4968

Kiran Penta

Role: primary

386-538-3169

Anamaria Astudillo

Role: primary

561-447-0614

Samuel Rosner, MD

Role: primary

410-328-2288

Kaylee Martin

Role: backup

410-328-2288

Heather Austin

Role: primary

585-216-7617

Catherine Maples

Role: primary

517-375-3057

Carrie Smith

Role: primary

330-492-3345 ext. 208

Kim Roby

Role: backup

330-492-3345 ext. 227

Marian Heaven, BSN

Role: primary

512-427-9400

Isabel Navarrete

Role: primary

833-832-8328

Dustyn Tobin, MD

Role: backup

833-832-8328

Steven M. Bettag, MD

Role: primary

920-452-1650

Related Links

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http://www.genelux.com

Sponsor's website

Other Identifiers

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Olvi-Vec-NSCLC-025

Identifier Type: -

Identifier Source: org_study_id

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