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

NCT06463665 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: Olvi-Vec-NSCLC-025
• Study Type: interventional
• Target: 142
• Locations: 1 country
• Sites: 16

Brief Summary

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.

Conditions

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

Keywords

Olvi-Vec; virotherapy; viral therapy; immunotherapy; immunochemotherapy; combination therapy; vaccinia virus; platinum-doublet chemotherapy; pembrolizumab; nivolumab; cemiplimab; atezolizumab; durvalumab; anti-PD-1; anti-PD-L1; carboplatin; cisplatin; docetaxel; neoplasms by site; neoplasms; carcinoma; Neoplasms by Histologic type; Antineoplastic Agents, Phytogenic; Antineoplastic Agents; Antimitotic Agents; Molecular Mechanisms of Pharmacological Action; Immune Checkpoint Inhibitors; NSCLC; NSCL cancer; chemoimmunotherapy; ICI; platinum resensitization; platinum resistant; chemoresistance; resensitize; olvimulogene nanivacirepvec

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 by Blinded Independent Central Review (BICR)

  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)

• Objective Response Rate (ORR) by RECIST 1.1

  From date of randomization up to 12 months.

• Median Overall Survival

  From date of randomization up to 36 months.

• Six-month Progression-free Survival Rate

  From date of randomization up to 6 months.

• Incidence of Treatment-emergent Adverse Events

  Assessed up to 36 months.

• Duration of Response by RECIST 1.1

  From date of randomization up to 12 months.

Study Arms (4)

Single-arm run-in Olvi-Vec dose escalation Cohorts

EXPERIMENTAL

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; Drug: Platinum chemotherapy: carboplatin or cisplatin; Drug: Non-platinum chemotherapy: paclitaxel or nab-paclitaxel for squamous cell NSCLC or pemetrexed for nonsquamous cell NSCLC; Drug: Physician's Choice of Immune Checkpoint Inhibitor: pembrolizumab, nivolumab, cemiplimab, atezolizumab, durvalumab

Experimental Arm

EXPERIMENTAL

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; Drug: Platinum chemotherapy: carboplatin or cisplatin; Drug: Non-platinum chemotherapy: paclitaxel or nab-paclitaxel for squamous cell NSCLC or pemetrexed for nonsquamous cell NSCLC; Drug: Physician's Choice of Immune Checkpoint Inhibitor: pembrolizumab, nivolumab, cemiplimab, atezolizumab, durvalumab

Active Comparator Arm

ACTIVE COMPARATOR

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

Drug: Docetaxel

Active Comparator Arm Cross-over

OTHER

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; Drug: Platinum chemotherapy: carboplatin or cisplatin; Drug: Non-platinum chemotherapy: paclitaxel or nab-paclitaxel for squamous cell NSCLC or pemetrexed for nonsquamous cell NSCLC; Drug: Physician's Choice of Immune Checkpoint Inhibitor: pembrolizumab, nivolumab, cemiplimab, atezolizumab, durvalumab; Drug: Docetaxel

Interventions

Olvimulogene nanivacirepvec BIOLOGICAL

Olvi-Vec is an engineered oncolytic vaccinia virus

Also known as: Olvi-Vec, GL-ONC, GLV-1h68

Active Comparator Arm Cross-over; Experimental Arm; Single-arm run-in Olvi-Vec dose escalation Cohorts

Platinum chemotherapy: carboplatin or cisplatin DRUG

Administered according to local practice.

Also known as: Brand of drug is based on institutional procurement

Active Comparator Arm Cross-over; Experimental Arm; Single-arm run-in Olvi-Vec dose escalation Cohorts

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

Administered according to local practice.

Also known as: Brand of drug is based on institutional procurement

Active Comparator Arm Cross-over; Experimental Arm; Single-arm run-in Olvi-Vec dose escalation Cohorts

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

Administered according to local practice.

Also known as: Brand of drug is based on institutional procurement

Active Comparator Arm Cross-over; Experimental Arm; Single-arm run-in Olvi-Vec dose escalation Cohorts

Docetaxel DRUG

Administered according to local practice.

Also known as: Brand of drug is based on institutional procurement

Active Comparator Arm; Active Comparator Arm Cross-over

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Genelux Corporation: lead
• Newsoara Biopharma Co., Ltd.: collaborator

Study Sites (16)

Pioneer Research Center, LLC

Bullhead City, Arizona, 86442, United States

RECRUITING

Clermont Oncology Center

Clermont, Florida, 34711, United States

RECRUITING

Oncology & Hematology Associates of West Broward

Coral Springs, Florida, 33065, United States

RECRUITING

Helios Clinical Research

Fort Lauderdale, Florida, 33316, United States

RECRUITING

Bioresearch Partner

Hialeah, Florida, 33013, United States

RECRUITING

University of Miami - Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

RECRUITING

Bioresearch Partner

Miami, Florida, 33155, United States

RECRUITING

Mid Florida Hematology and Oncology Center

Orange City, Florida, 32763, United States

RECRUITING

BRCR Medical Center, Inc.

Plantation, Florida, 33322, United States

RECRUITING

University of Maryland Medical Center Greenebaum Comprehensive Cancer Center

Baltimore, Maryland, 21201, United States

RECRUITING

Michigan Hematology and Oncology Consultants

Dearborn, Michigan, 48126, United States

RECRUITING

Oakland Medical Group

Farmington Hills, Michigan, 48336, United States

RECRUITING

Gabrail Cancer and Research Center

Canton, Ohio, 44718, United States

RECRUITING

Texas Oncology - Austin Central

Austin, Texas, 78745, United States

RECRUITING

World Research Link

Baytown, Texas, 77521, United States

RECRUITING

Sheboygan Cancer & Blood Center

Sheboygan, Wisconsin, 53081, United States

RECRUITING

Related Links

• Sponsor's website

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Vaccinia; Neoplasms by Site; Neoplasms; Carcinoma; Neoplasms by Histologic Type

Interventions

Cisplatin; 130-nm albumin-bound paclitaxel; Pemetrexed; Nivolumab; cemiplimab; atezolizumab; durvalumab; Docetaxel

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Poxviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Neoplasms, Glandular and Epithelial

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: June 11, 2024
• First Posted: June 18, 2024
• Study Start: September 26, 2024
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): July 1, 2029
• Last Updated: September 26, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (16)