Trial Title:
Efficacy & Safety of Olvimulogene Nanivacirepvec & Platinum-doublet + Physician's Choice of Immune Checkpoint Inhibitor Compared to Docetaxel in NSCL Cancer
NCT ID:
NCT06463665
Condition:
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
Conditions: Official terms:
Carcinoma
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Paclitaxel
Docetaxel
Carboplatin
Pembrolizumab
Nivolumab
Pemetrexed
Atezolizumab
Durvalumab
Cemiplimab
Immune Checkpoint Inhibitors
Conditions: 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
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Crossover Assignment
Intervention model description:
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 purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
Olvimulogene nanivacirepvec
Description:
Olvi-Vec is an engineered oncolytic vaccinia virus
Arm group label:
Active Comparator Arm Cross-over
Arm group label:
Experimental Arm
Arm group label:
Single-arm run-in Olvi-Vec dose escalation Cohorts
Other name:
Olvi-Vec
Other name:
GL-ONC
Other name:
GLV-1h68
Intervention type:
Drug
Intervention name:
Platinum chemotherapy: carboplatin or cisplatin
Description:
Administered according to local practice.
Arm group label:
Active Comparator Arm Cross-over
Arm group label:
Experimental Arm
Arm group label:
Single-arm run-in Olvi-Vec dose escalation Cohorts
Other name:
Brand of drug is based on institutional procurement
Intervention type:
Drug
Intervention name:
Non-platinum chemotherapy: paclitaxel or nab-paclitaxel for squamous cell NSCLC or pemetrexed for nonsquamous cell NSCLC
Description:
Administered according to local practice.
Arm group label:
Active Comparator Arm Cross-over
Arm group label:
Experimental Arm
Arm group label:
Single-arm run-in Olvi-Vec dose escalation Cohorts
Other name:
Brand of drug is based on institutional procurement
Intervention type:
Drug
Intervention name:
Physician's Choice of Immune Checkpoint Inhibitor: pembrolizumab, nivolumab, cemiplimab, atezolizumab, durvalumab
Description:
Administered according to local practice.
Arm group label:
Active Comparator Arm Cross-over
Arm group label:
Experimental Arm
Arm group label:
Single-arm run-in Olvi-Vec dose escalation Cohorts
Other name:
Brand of drug is based on institutional procurement
Intervention type:
Drug
Intervention name:
Docetaxel
Description:
Administered according to local practice.
Arm group label:
Active Comparator Arm
Arm group label:
Active Comparator Arm Cross-over
Other name:
Brand of drug is based on institutional procurement
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.
Criteria for eligibility:
Criteria:
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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
BRCR Medical Center, Inc.
Address:
City:
Plantation
Zip:
33322
Country:
United States
Status:
Recruiting
Contact:
Last name:
Maria del Carme Ibanez
Phone:
561-447-0614
Email:
mcarmei@brcrglobal.com
Investigator:
Last name:
Harshad Amin, MD
Email:
Principal Investigator
Start date:
September 26, 2024
Completion date:
July 2029
Lead sponsor:
Agency:
Genelux Corporation
Agency class:
Industry
Collaborator:
Agency:
Newsoara Biopharma Co., Ltd.
Agency class:
Industry
Source:
Genelux Corporation
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06463665
http://www.genelux.com
