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.
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
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
142
Olvi-Vec is an engineered oncolytic vaccinia virus
Administered according to local practice.
Administered according to local practice.
Administered according to local practice.
Administered according to local practice.
Pioneer Research Center, LLC
Bullhead City, Arizona, United States
RECRUITINGClermont Oncology Center
Clermont, Florida, United States
RECRUITINGOncology & Hematology Associates of West Broward
Coral Springs, Florida, United States
RECRUITINGHelios Clinical Research
Fort Lauderdale, Florida, United States
RECRUITINGBioresearch Partner
Hialeah, Florida, United States
RECRUITINGUniversity of Miami - Sylvester Comprehensive Cancer Center
Miami, Florida, United States
RECRUITINGBioresearch Partner
Miami, Florida, United States
RECRUITINGMid Florida Hematology and Oncology Center
Orange City, Florida, United States
RECRUITINGBRCR Medical Center, Inc.
Plantation, Florida, United States
RECRUITINGUniversity of Maryland Medical Center Greenebaum Comprehensive Cancer Center
Baltimore, Maryland, United States
RECRUITING...and 6 more locations
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.
Time frame: From date of randomization up to 12 months.
Objective Response Rate (ORR) by RECIST 1.1
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.
Time frame: From date of randomization up to 12 months.
Median Overall Survival
Time from randomization until death or study completion; assessed up to 36 months.
Time frame: From date of randomization up to 36 months.
Six-month Progression-free Survival Rate
Proportion of patients who remained alive and progression-free at 6 months.
Time frame: From date of randomization up to 6 months.
Incidence of Treatment-emergent Adverse Events
From date of first study treatment until death or study completion.
Time frame: Assessed up to 36 months.
Duration of Response by RECIST 1.1
Time from date of first response until the first date of progressive disease based on radiological assessment.
Time frame: From date of randomization up to 12 months.
Disease Control Rate (DCR)
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.
Time frame: From date of randomization up to 12 months.
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