Virus Therapy and Chemotherapy for Lung Cancer

(VIRO-25 Trial)

Recruiting at 15 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Genelux Corporation

Must not be taking: Antivirals, Immunosuppressants

Disqualifiers: Infections, CNS metastasis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 12 months

142 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new virus-based treatment, Olvi-Vec (also known as Olvimulogene Nanivacirepvec), for individuals with advanced lung cancer that hasn't responded well to initial treatments. Researchers aim to determine if this virus therapy, followed by standard chemotherapy and a chosen immune therapy, is more effective than the usual chemotherapy drug, docetaxel. Individuals with non-small-cell lung cancer (NSCLC) who have experienced disease progression after initial treatments might be suitable candidates for this study. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that Olvimulogene Nanivacirepvec, or Olvi-Vec, was safe in earlier studies. When combined with chemotherapy, Olvi-Vec effectively controlled small cell lung cancer. The side effects are generally mild and manageable. Studies have also demonstrated positive outcomes, such as tumor shrinkage and partial improvements, indicating the treatment's effectiveness against cancer.

Although more research is needed, the current findings offer encouragement for those considering joining the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard chemotherapy options for lung cancer, Olvimulogene Nanivacirepvec, or Olvi-Vec, is a virus-based therapy that specifically targets and kills cancer cells while sparing normal cells. This approach offers a new mechanism of action compared to traditional treatments like docetaxel or platinum-doublet chemotherapy. Researchers are excited because Olvi-Vec could potentially enhance the effectiveness of chemotherapy by weakening the cancer cells, making them more susceptible to treatment. Additionally, its ability to trigger an immune response against the tumor may lead to longer-lasting effects, offering hope for improved outcomes in lung cancer patients.

What evidence suggests that this trial's treatments could be effective for lung cancer?

Research has shown that Olvimulogene Nanivacirepvec (Olvi-Vec), which participants in the Experimental Arm of this trial may receive, may help treat lung cancer. In one study, Olvi-Vec combined with chemotherapy stopped the disease from growing or spreading in 71% of patients with resistant small cell lung cancer, effectively controlling the cancer in most patients. Another study found that Olvi-Vec, when used with chemotherapy, controlled cancer that had returned after initial treatment. These early results suggest that Olvi-Vec could be useful in managing non-small-cell lung cancer, especially when standard treatments are not effective. ^{1 2 5 6 7}

Are You a Good Fit for This Trial?

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 can carry out all my usual activities without help.

My lung cancer is confirmed to be advanced or has spread.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Docetaxel
• Olvimulogene Nanivacirepvec
• Physician's Choice of Immune Checkpoint Inhibitor

Trial Overview

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.

How Is the Trial Designed?

Group I: Single-arm run-in Olvi-Vec dose escalation Cohorts Experimental Treatment 4 Interventions

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.

Group II: Experimental Arm Experimental Treatment 4 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-over Experimental Treatment 5 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 Arm Active Control 1 Intervention

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

Who Is Running the Clinical Trial?

Genelux Corporation

Lead Sponsor

Trials

8

Recruited

460+

Newsoara Biopharma Co., Ltd.

Industry Sponsor

Trials

9

Recruited

1,100+

Newsoara BHK BioPharma Co. Ltd.

Industry Sponsor

Newsoara HYK Biopharmaceutical (Shanghai) Co., Ltd.

Industry Sponsor

Published Research Related to This Trial

The combination of the oncolytic virus ReoT3D with the chemotherapeutics irinotecan (CPT-11) and napabucasin (BBI608) showed a synergistic anticancer effect against murine colorectal cancer cells (CT26), significantly enhancing apoptosis and reducing cell migration.

Individually, each treatment effectively induced apoptosis and cell cycle arrest, but the strongest anticancer response was observed when all three agents were used together, suggesting a promising new strategy for colorectal cancer treatment in future clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The synergistic anticancer effects of ReoT3D, CPT-11, and BBI608 on murine colorectal cancer cells. Babaei, A., Soleimanjahi, H., Soleimani, M., et al.[2021]

Recent studies show that novel monoclonal antibodies targeting the PD-1 or PD-L1 pathways, like nivolumab and pembrolizumab, significantly improve overall survival in patients with advanced non-small cell lung cancer (NSCLC) after failure of platinum-based chemotherapy.

In contrast, traditional second-line treatments such as pemetrexed, docetaxel, and EGFR inhibitors have not shown improvements in overall survival, highlighting the effectiveness of immune checkpoint inhibitors as the new standard of care for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Second-Line Treatment of Non-Small Cell Lung Cancer: New Developments for Tumours Not Harbouring Targetable Oncogenic Driver Mutations. Barnfield, PC., Ellis, PM.[2019]

Oncolytic viruses (OVs), like talimogene laherparepvec (T-VEC), are a promising cancer treatment that selectively target tumor cells, induce immune responses, and have a favorable safety profile compared to traditional therapies.

T-VEC is currently the only widely approved OV for treating recurrent melanoma, and while there is growing clinical data supporting its use, further research is needed to fully understand the biology and optimize the application of OVs in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapy with oncolytic viruses: progress and challenges. Shalhout, SZ., Miller, DM., Emerick, KS., et al.[2023]

In a review of 19 clinical trials involving 5,038 patients with non-small cell lung carcinoma (NSCLC), PD-1 inhibitors were found to have a significantly higher incidence of any grade pneumonitis (3.6%) compared to PD-L1 inhibitors (1.3%).

Treatment naive patients experienced a higher incidence of pneumonitis (4.3%) than those who had previously received treatment (2.8%), indicating that prior chemotherapy may reduce the risk of this side effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Khunger, M., Rakshit, S., Pasupuleti, V., et al.[2022]

Bevacizumab, a drug used in combination with chemotherapy for non-small cell lung cancer, can lead to serious gastrointestinal complications, such as colonic perforation, even in patients without known risk factors.

A case study of a 69-year-old patient revealed that after two cycles of chemotherapy including bevacizumab, the patient developed ischemic colitis, highlighting the need for vigilance in monitoring for abdominal pain in patients receiving this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bowel perforation in non-small cell lung cancer after bevacizumab therapy. Schellhaas, E., Loddenkemper, C., Schmittel, A., et al.[2021]

L-BLP25 is an immunotherapy that specifically targets the MUC1 antigen, which is associated with non-small cell lung cancer (NSCLC), and has shown promise in inducing a T-cell response in both animal models and human patients.

Clinical trials have indicated that using L-BLP25 as maintenance therapy after standard chemotherapy may improve outcomes for patients with advanced NSCLC, potentially enhancing overall survival beyond the current median of 10 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

L-BLP25 as a peptide vaccine therapy in non-small cell lung cancer: a review. Xia, W., Wang, J., Xu, Y., et al.[2020]

In the phase III SAPPHIRE study involving 577 patients with advanced non-small-cell lung cancer, the combination of sitravatinib and nivolumab did not significantly improve overall survival compared to docetaxel, with median survival times of 12.2 months versus 10.6 months, respectively.

However, the combination therapy showed a better clinical benefit rate (75.5% vs. 64.5%) and a lower incidence of grade ≥3 treatment-related adverse events (53.0% vs. 66.7%), suggesting a potentially safer profile despite not meeting the primary survival endpoint.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SAPPHIRE: phase III study of sitravatinib plus nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. Borghaei, H., de Marinis, F., Dumoulin, D., et al.[2023]

Antibodies targeting the PD-1/PD-L1 axis can effectively restore anti-tumor immunity, showing promise in treating various tumor types, including non-small cell lung cancer.

A case study of a patient with advanced KRAS mutant pulmonary adenocarcinoma revealed an excellent response to a single dose of nivolumab, highlighting the importance of evaluating exceptional responders to understand treatment mechanisms and resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Near complete response after single dose of nivolumab in patient with advanced heavily pre-treated KRAS mutant pulmonary adenocarcinoma. Davar, D., Socinski, MA., Dacic, S., et al.[2020]

In a study of 123 patients with advanced NSCLC resistant to EGFR-TKIs, combining PD-1/L1 inhibitors with chemotherapy and anti-angiogenic drugs significantly improved progression-free survival (PFS) and overall survival (OS) compared to monotherapy or chemotherapy alone.

Patients receiving the combination treatment (ICIs+BCP) had a PFS of 9.5 months and an OS of 16.97 months, indicating that this approach may be more effective for managing advanced NSCLC in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world study of PD-1/L1 immune checkpoint inhibitors for advanced non-small cell lung cancer after resistance to EGFR-TKIs. Wei, K., Zhou, C., Chen, Y., et al.[2023]

OncoViron, an oncolytic adenovirus, effectively targets and inhibits the growth of various solid tumors, demonstrating significant anticancer effects in multiple implanted tumor models in mice.

The treatment not only enhances the immune response by recruiting immune cells and altering the tumor microenvironment but also shows promising results when combined with immunotherapies like PD-1 antibodies and CAR T cells, indicating its potential for synergistic cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Triple-serotype chimeric oncolytic adenovirus exerts multiple synergistic mechanisms against solid tumors. Su, Y., Li, J., Ji, W., et al.[2022]

The study developed a vaccinia-based oncolytic virus (OV) that incorporates gene reporters (hNIS and hSSR2) to enhance both the treatment and visualization of tumors, showing improved efficacy in targeting cancer cells.

Using a late synthetic promoter for hNIS expression allowed for better functional performance and imaging capabilities, demonstrating that the modified OV can effectively infect tumors and provide diagnostic signals for tumor regression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhancing Expression of Functional Human Sodium Iodide Symporter and Somatostatin Receptor in Recombinant Oncolytic Vaccinia Virus for In Vivo Imaging of Tumors. Wang, J., Arulanandam, R., Wassenaar, R., et al.[2018]

Oncolytic virotherapy is a promising strategy that uses viruses to selectively kill lung cancer cells and stimulate the immune system to fight tumors, showing potential as a complementary approach to existing treatments like immune checkpoint inhibitors.

Despite its promise, oncolytic virotherapy is not yet a standard treatment for lung cancer and requires further research to fully understand its mechanisms and effectiveness in combination with current therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lung cancer and oncolytic virotherapy--enemy's enemy. Li, Z., Feiyue, Z., Gaofeng, L., et al.[2022]

In a study of 56 patients with EGFR-mutated lung cancer who had progressed on EGFR-TKI treatment, combining PD-1 inhibitors with chemotherapy or bevacizumab resulted in a disease control rate of 53.6% and an objective response rate of 10.7%.

The combination therapy showed a median progression-free survival of 3.33 months, with better outcomes observed in patients receiving PD-1 inhibitors as second-line therapy compared to later lines, indicating moderate efficacy and an acceptable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune checkpoint inhibitors combined with chemotherapy/bevacizumab therapy for patients with advanced lung cancer and heavily treated with EGFR mutation: a retrospective analysis. Hu, R., Zhao, Z., Shi, Y., et al.[2022]

Bevacizumab, an angiogenesis inhibitor, has been shown to significantly prolong overall survival and progression-free survival in patients with inoperable, advanced non-small-cell lung cancer when used with chemotherapy, based on two recent phase-III studies.

While bevacizumab can cause manageable side effects like hypertension and proteinuria, careful patient selection can minimize the risk of serious complications such as pulmonary bleeding.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Bevacizumab in the first-line therapy of advanced NSCLC]. Hasenöhrl, N.[2018]

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The VIRO-25 trial is an open-label, randomized study evaluating the safety and efficacy of intravenously delivered olvi-vec followed by platinum-doublet ...