Virus Therapy and Chemotherapy for Lung Cancer
(VIRO-25 Trial)
Recruiting in Palo Alto (17 mi)
+4 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Genelux Corporation
Must not be taking: Antivirals, Immunosuppressants
Disqualifiers: Infections, CNS metastasis, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?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.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you are taking antiviral agents active against vaccinia virus or require more than 10 mg of prednisone (a type of steroid) per day.
What data supports the effectiveness of the drug combination used in the Virus Therapy and Chemotherapy for Lung Cancer trial?
Research shows that immune checkpoint inhibitors, like nivolumab, can restore the body's ability to fight cancer and have been effective in treating non-small cell lung cancer. Additionally, docetaxel is an approved second-line treatment for lung cancer, suggesting potential benefits when combined with other therapies.
12345Is the combination of virus therapy and chemotherapy for lung cancer generally safe in humans?
Immune checkpoint inhibitors, which are part of the treatment, have shown good safety in patients with advanced lung cancer, but they can sometimes cause pneumonitis (lung inflammation). Bevacizumab, another drug used in combination, is generally well-tolerated but can cause hypertension (high blood pressure) and proteinuria (protein in urine), and in rare cases, bowel perforation (a hole in the bowel).
36789What makes the treatment Olvimulogene Nanivacirepvec unique for lung cancer?
Olvimulogene Nanivacirepvec is unique because it uses oncolytic virotherapy, which involves a virus that specifically targets and kills cancer cells while also stimulating the immune system to attack the tumor, offering a novel approach compared to traditional chemotherapy or immunotherapy.
1011121314Eligibility Criteria
This trial is for adults over 18 with advanced or metastatic non-small cell lung cancer (NSCLC) who've had progression after initial treatment. They should have received 2-6 cycles of platinum-based chemo with immune therapy and be in good physical condition (ECOG status 0 or 1). Pregnant women can't participate, and participants must have adequate organ function.Inclusion Criteria
I am a woman who can have children and have a negative pregnancy test.
I am 18 years old or older.
I can carry out all my usual activities without help.
+7 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive Olvi-Vec followed by platinum-doublet chemotherapy and Physician's Choice of Immune Checkpoint Inhibitor or docetaxel
Up to 12 months
Regular visits as per treatment protocol
Follow-up
Participants are monitored for safety and effectiveness after treatment
Up to 36 months
Open-label extension (optional)
Participants in the Active Comparator Arm may cross-over to receive treatment as per the Experimental Arm after disease progression
Until disease progression or study completion
Participant Groups
The study compares Olvimulogene Nanivacirepvec (an oncolytic virus) followed by platinum-doublet chemotherapy plus a physician's choice of an immune checkpoint inhibitor against the standard drug Docetaxel. It aims to see which is more effective and safe for NSCLC patients after their first disease progression.
4Treatment groups
Experimental Treatment
Active Control
Group I: Single-arm run-in Olvi-Vec dose escalation CohortsExperimental Treatment4 Interventions
Cohort 1: Olvi-Vec administered over 3 consecutive days at 1,2,3 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 2,3,5 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 2,3,5,5 x 10e9 pfu followed 2 to 3 weeks later with platinum-doublet chemotherapy + Physician's Choice of ICI.
Group II: Experimental ArmExperimental Treatment4 Interventions
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 III: Active Comparator Arm Cross-overExperimental Treatment5 Interventions
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 IV: Active Comparator ArmActive Control1 Intervention
Docetaxel starts in Week 0 and continues until disease progression is assessed by the BICR.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
BRCR Medical Center, Inc.Plantation, FL
University of Miami - Sylvester Comprehensive Cancer CenterMiami, FL
Michigan Hematology and Oncology ConsultantsDearborn, MI
Oakland Medical GroupFarmington Hills, MI
More Trial Locations
Loading ...
Who Is Running the Clinical Trial?
Genelux CorporationLead Sponsor
Newsoara Biopharma Co., Ltd.Industry Sponsor
References
L-BLP25 as a peptide vaccine therapy in non-small cell lung cancer: a review. [2020]Lung cancer is one of the most prevalent malignancies worldwide and the leading cause of cancer-related death. Most cases are non-small cell lung cancer (NSCLC). The median overall survival of patients with advanced stage undergoing current standard chemotherapy is approximately 10 months. The addition of new compounds, including targeted agents, to standard first-line cytotoxic doublets, which are administered concurrently and/or as maintenance therapy in patients who have not experienced disease progression after first-line treatment, has shown potential in improving the efficacy in patients with advanced disease. L-BLP25 is a mucin 1 (MUC1) antigen-specific immunotherapy induces a T-cell response to MUC1 in both a preclinical MUC1-transgenic lung cancer mouse model and patients. This review is aimed at introducing the mechanism by which L-BLP25 targets MUC1, summarizing the achievements gained in the completed clinical trials with L-BLP25 administered as maintenance therapy in the treatment of unresectable stage III/IV NSCLC, and discussing the research trends.
SAPPHIRE: phase III study of sitravatinib plus nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. [2023]Checkpoint inhibitor (CPI) therapy revolutionized treatment for advanced non-small-cell lung cancer (NSCLC); however, most patients progress due to primary or acquired resistance. Sitravatinib is a receptor tyrosine kinase inhibitor that can shift the immunosuppressive tumor microenvironment toward an immunostimulatory state. Combining sitravatinib with nivolumab (sitra + nivo) may potentially overcome initial CPI resistance.
Immune checkpoint inhibitors combined with chemotherapy/bevacizumab therapy for patients with advanced lung cancer and heavily treated with EGFR mutation: a retrospective analysis. [2022]EGFR-mutated lung cancer poorly responded to anti-programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) monotherapy. Whether patients with EGFR-mutated lung cancer can benefit from anti-PD-1/PD-L1 therapy combined with other drugs remains controversial. We retrospectively evaluated the safety and efficacy of the PD-1 inhibitor combined with other drugs (chemotherapy and/or bevacizumab) in patients with EGFR-mutated lung cancer, who have progressed on EGFR-TKI treatment to determine the activity of the anti-PD-1/PD-L1 therapy combined with chemotherapy or/and bevacizumab therapy in heavily treated patients with EGFR-mutated lung cancer.
Near complete response after single dose of nivolumab in patient with advanced heavily pre-treated KRAS mutant pulmonary adenocarcinoma. [2020]The programmed death 1 (PD-1) receptor is expressed by activated T-cells and engaged by ligands PD-L1 and PD-L2 normally expressed by infiltrating immune cells in response to viral infection. The PD-1/PD-L1 axis is a negative inhibitory pathway that down-regulates T-cells but is also used by tumors to evade anti-tumor immunity. Antibodies targeting PD-1/PD-L1 axis are capable of restoring functional anti-tumor immunity and have demonstrated efficacy in a broad range of tumor types including non-small cell lung cancer in both squamous and adenocarcinoma histologies. Ongoing issues affecting clinical development of these agents include assessment of response, optimal duration of therapy in excellent responders, predictive biomarkers and mechanisms of resistance. In this report, we describe a patient with advanced KRAS mutant heavily pretreated pulmonary adenocarcinoma who developed an excellent response after a single-dose of nivolumab. Pre-treatment tumor was found to have moderate CD3 and PD-L1 positivity by immunohistochemical staining. Evaluation of exceptional responders and non-responders are critical to furthering our understanding of the mechanisms of action (and resistance) to these agents.
Second-Line Treatment of Non-Small Cell Lung Cancer: New Developments for Tumours Not Harbouring Targetable Oncogenic Driver Mutations. [2019]Platinum-based doublet chemotherapy with or without bevacizumab is the standard of care for the initial management of advanced and metastatic non-small cell lung cancer (NSCLC) without a targetable molecular abnormality. However, the majority of patients with NSCLC will ultimately develop resistance to initial platinum-based chemotherapy, and many remain candidates for subsequent lines of therapy. Randomised trials over the past 10-15 years have established pemetrexed (non-squamous histology), docetaxel, erlotinib and gefitinib as approved second-line agents in NSCLC without targetable driver mutations or rearrangements. Trials comparing these agents with other chemotherapy, evaluating the addition of an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) to chemotherapy or the addition of another targeted agent to erlotinib or gefitinib have all failed to demonstrate an improvement in overall survival for patients with NSCLC. In contrast, recent data comparing therapy with novel monoclonal antibodies against programmed cell death 1 (PD-1) or PD ligand (PD-L1) pathway versus standard chemotherapy following platinum failure have demonstrated significant improvements in overall survival. Therapy with nivolumab or pembrolizumab would now be considered standard second-line therapy in patients without contraindication to immune checkpoint inhibitors. Atezolizumab also appears promising in this setting.
Real-world study of PD-1/L1 immune checkpoint inhibitors for advanced non-small cell lung cancer after resistance to EGFR-TKIs. [2023]Programmed cell death-1 (PD-1) and its ligand 1 (PD-L1) inhibitors have achieved good efficacy and safety in patients with advanced EGFR mutation-negative non-small cell lung cancer (NSCLC), but their efficacy in patients with previous EGFR mutations is limited. The aim of the present study was to explore the efficacy of PD-1/L1 immune checkpoint inhibitors for the treatment of patients with advanced NSCLC who are resistant to EGFR-TKIs.
[Bevacizumab in the first-line therapy of advanced NSCLC]. [2018]The angiogenesis inhibitor bevacizumab, a VEGF antagonist, was approved in the European Union in August 2007 for the first-line therapy of inoperable, advanced or recurrent non-small-cell lung cancer, in combination with a platin-based chemotherapy regimen. Tumors with predominantly squamous-cell histology must be excluded. Two recent phase-III studies have shown that bevacizumab, combined with carboplatin and paclitaxel (E4599) or cisplatin and gemcitabine (AVAiL), significantly prolongs overall survival and/or progression-free survival. The most common adverse events during therapy with bevacizumab are hypertension and proteinuria - both are usually well manageable. By applying correct patient selection criteria the risk of pulmonary bleeding can be greatly reduced.
Incidence of Pneumonitis With Use of Programmed Death 1 and Programmed Death-Ligand 1 Inhibitors in Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis of Trials. [2022]Programmed death 1 (PD-1) programmed death-ligand 1 (PD-L1) inhibitors show significant clinical activity in non-small cell lung carcinoma (NSCLC). However, they are often associated with potentially fatal immune-mediated pneumonitis. Preliminary reports of trials suggest a difference in the rate of pneumonitis with PD-1 and PD-L1 inhibitors. We sought to determine the overall incidence of pneumonitis and differences according to type of inhibitors and prior chemotherapy use.
Bowel perforation in non-small cell lung cancer after bevacizumab therapy. [2021]Bevacizumab is increasingly used in combination with chemotherapy for treatment of unresectable non-small cell lung cancer. The aim of this report is to underline possible risks associated with this otherwise well-tolerated drug.
Triple-serotype chimeric oncolytic adenovirus exerts multiple synergistic mechanisms against solid tumors. [2022]Oncolytic virotherapy has become an important branch of cancer immunotherapy. This study investigated the efficacy of an oncolytic adenovirus (OAV), OncoViron, with synergistic mechanisms in the treatment of multiple solid tumors.
Therapy with oncolytic viruses: progress and challenges. [2023]Oncolytic viruses (OVs) are an emerging class of cancer therapeutics that offer the benefits of selective replication in tumour cells, delivery of multiple eukaryotic transgene payloads, induction of immunogenic cell death and promotion of antitumour immunity, and a tolerable safety profile that largely does not overlap with that of other cancer therapeutics. To date, four OVs and one non-oncolytic virus have been approved for the treatment of cancer globally although talimogene laherparepvec (T-VEC) remains the only widely approved therapy. T-VEC is indicated for the treatment of patients with recurrent melanoma after initial surgery and was initially approved in 2015. An expanding body of data on the clinical experience of patients receiving T-VEC is now becoming available as are data from clinical trials of various other OVs in a range of other cancers. Despite increasing research interest, a better understanding of the underlying biology and pharmacology of OVs is needed to enable the full therapeutic potential of these agents in patients with cancer. In this Review, we summarize the available data and provide guidance on optimizing the use of OVs in clinical practice, with a focus on the clinical experience with T-VEC. We describe data on selected novel OVs that are currently in clinical development, either as monotherapies or as part of combination regimens. We also discuss some of the preclinical, clinical and regulatory hurdles that have thus far limited the development of OVs.
Enhancing Expression of Functional Human Sodium Iodide Symporter and Somatostatin Receptor in Recombinant Oncolytic Vaccinia Virus for In Vivo Imaging of Tumors. [2018]Oncolytic virus (OV) therapy has emerged as a novel tool in our therapeutic arsenals for fighting cancer. As a live biologic agent, OV has the ability to target and selectively amplify at the tumor sites. We have reported that a vaccinia-based OV (Pexa-Vec) has shown good efficacy in preclinical models and in clinical trials. To give an additional tool to clinicians to allow both treatment of the tumor and improved visualization of tumor margins, we developed new viral-based platforms with 2 specific gene reporters.
The synergistic anticancer effects of ReoT3D, CPT-11, and BBI608 on murine colorectal cancer cells. [2021]Many types of oncolytic viruses (OVs) were enrolled in clinical trials. Recently, an OV named Talimogene laherparepvec approved for the treatment of melanoma. This achievement highlighted the clinical application of OVs. Scientists focus on using these anticancer agents in combination with the current or/and new anticancer chemotherapeutics. They aim to increase the oncolytic effect of a new approach for the treatment of cancer cells.
Lung cancer and oncolytic virotherapy--enemy's enemy. [2022]Lung cancer is one of the malignant tumors that seriously threaten human health worldwide, while the covid-19 virus has become people's nightmare after the coronavirus pandemic. There are too many similarities between cancer cells and viruses, one of the most significant is that both of them are our enemies. The strategy to take the advantage of the virus to beat cancer cells is called Oncolytic virotherapy. When immunotherapy represented by immune checkpoint inhibitors has made remarkable breakthroughs in the clinical practice of lung cancer, the induction of antitumor immunity from immune cells gradually becomes a rapidly developing and promising strategy of cancer therapy. Oncolytic virotherapy is based on the same mechanisms that selectively kill tumor cells and induce systemic anti-tumor immunity, but still has a long way to go before it becomes a standard treatment for lung cancer. This article provides a comprehensive review of the latest progress in oncolytic virotherapy for lung cancer, including the specific mechanism of oncolytic virus therapy and the main types of oncolytic viruses, and the combination of oncolytic virotherapy and existing standard treatments. It aims to provide new insights and ideas on oncolytic virotherapy for lung cancer.