Virus Therapy and Chemotherapy for Lung Cancer

(VIRO-25 Trial)

Recruiting at 9 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

Trial Summary

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. ^{1 2 3 4 5}

Is 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). ^{3 6 7 8 9}

What 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. ^{10 11 12 13 14}

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.

Eligibility 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 can carry out all my usual activities without help.

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

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

Treatment Details

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.

Participant Groups

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 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 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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

1. China pubmed.ncbi.nlm.nih.gov

L-BLP25 as a peptide vaccine therapy in non-small cell lung cancer: a review. [2020]

2. England pubmed.ncbi.nlm.nih.gov

SAPPHIRE: phase III study of sitravatinib plus nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. [2023]

3. China 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. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Near complete response after single dose of nivolumab in patient with advanced heavily pre-treated KRAS mutant pulmonary adenocarcinoma. [2020]

5. New Zealand pubmed.ncbi.nlm.nih.gov

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

6. Switzerland 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. [2023]

7. Austria pubmed.ncbi.nlm.nih.gov

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

8. United States 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. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Bowel perforation in non-small cell lung cancer after bevacizumab therapy. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Triple-serotype chimeric oncolytic adenovirus exerts multiple synergistic mechanisms against solid tumors. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Therapy with oncolytic viruses: progress and challenges. [2023]

12. United States 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. [2018]

13. Switzerland pubmed.ncbi.nlm.nih.gov

The synergistic anticancer effects of ReoT3D, CPT-11, and BBI608 on murine colorectal cancer cells. [2021]

14. United States pubmed.ncbi.nlm.nih.gov

Lung cancer and oncolytic virotherapy--enemy's enemy. [2022]