Efficacy & Safety of Olvimulogene Nanivacirepvec & Platinum-doublet + Physician's Choice of Immune Checkpoint Inhibitor Compared to Docetaxel in NSCL Cancer
Start Date
9/26/2024
Completion Date
7/1/2029
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.
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.
Eligibility Criteria
Age Range: 18 years to No maximum
Interventions
Olvimulogene nanivacirepvec
Platinum chemotherapy: carboplatin or cisplatin
Non-platinum chemotherapy: paclitaxel or nab-paclitaxel for squamous cell NSCLC or pemetrexed for nonsquamous cell NSCLC
Physician's Choice of Immune Checkpoint Inhibitor: pembrolizumab, nivolumab, cemiplimab, atezolizumab, durvalumab
Docetaxel
Conditions
Locations
Pioneer Research Center, LLC
Bullhead City, Arizona 86442
United States
Clermont Oncology Center
Clermont, Florida 34711
United States
Oncology & Hematology Associates of West Broward
Coral Springs, Florida 33065
United States
Helios Clinical Research
Fort Lauderdale, Florida 33316
United States
Bioresearch Partner
Hialeah, Florida 33013
United States
University of Miami - Sylvester Comprehensive Cancer Center
Miami, Florida 33136
United States
Bioresearch Partner
Miami, Florida 33155
United States
Mid Florida Hematology and Oncology Center
Orange City, Florida 32763
United States
BRCR Medical Center, Inc.
Plantation, Florida 33322
United States
Michigan Hematology and Oncology Consultants
Dearborn, Michigan 48126
United States
Oakland Medical Group
Farmington Hills, Michigan 48336
United States
Inspira Medical Center Mullica Hill
Mullica Hill, New Jersey 08062
United States
Gabrail Cancer and Research Center
Canton, Ohio 44718
United States
Texas Oncology - Austin Central
Austin, Texas 78745
United States
World Research Link
Baytown, Texas 77521
United States