VG2025 + Nivolumab for Advanced Cancer

Recruiting in Palo Alto (17 mi)

+1 other location

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Virogin Biotech Canada Ltd

Must not be taking: Antivirals, Corticosteroids, Anticoagulants, others

Disqualifiers: CNS malignancy, Heart failure, Autoimmune, others

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial is testing a new treatment called VG2025, alone or combined with Nivolumab, in patients with advanced malignant solid tumors. VG2025 is injected directly into tumors to kill cancer cells, while Nivolumab helps the immune system fight cancer. The goal is to find effective treatments for patients who have not responded to standard therapies.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you must not have taken immunotherapy, systemic chemotherapy, or certain other treatments within a specific time before starting the trial. It's best to discuss your current medications with the trial team to see if they might affect your eligibility.

What data supports the effectiveness of the drug VG2025 + Nivolumab for advanced cancer?

Nivolumab, a part of the treatment, has shown to improve survival in patients with advanced cancers like lung cancer, melanoma, and renal cancer by enhancing the immune system's ability to fight tumors. Combining nivolumab with other therapies has been shown to overcome resistance and improve its effectiveness in cancer treatment. ^{1 2 3 4 5}

Is the combination of VG2025 and Nivolumab safe for humans?

Nivolumab, a drug used in cancer treatment, has been associated with immune-related side effects, including rare but serious neurological effects like encephalitis (inflammation of the brain). These side effects can often be managed by stopping the drug and using treatments like steroids. ^{6 7 8 9 10}

What makes the drug VG2025 + Nivolumab unique for advanced cancer?

The combination of VG2025 with Nivolumab is unique because it pairs a novel treatment (VG2025) with Nivolumab, an immune checkpoint inhibitor that enhances the body's immune response against cancer. This combination aims to overcome resistance seen in many patients when using Nivolumab alone, potentially improving treatment effectiveness for advanced cancer. ^{2 5 11 12 13}

Research Team

Eligibility Criteria

Adults with advanced solid tumors that have not responded to standard treatments or for whom no standard treatment is available. Participants must be in relatively good physical condition (ECOG 0 or 1), not have serious heart conditions, infections, or autoimmune diseases, and agree to use effective contraception.

Inclusion Criteria

I am fully active or restricted in physically strenuous activity but can do light work.

I agree to avoid pregnancy during and 6 months after the study by abstaining or using strong contraception.

ANC ≥1.5 × 10^9/L

Exclusion Criteria

Known to test positive for human immunodeficiency virus (HIV), hepatitis B or C virus, or syphilis

I cannot stop my blood thinners safely for cancer treatment procedures.

I haven't been in a drug trial with long-lasting effects in the last month.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive VG2025 as intratumoral injections biweekly, with dose-escalation design in monotherapy and combination therapy arms

4 weeks

Biweekly visits for intratumoral injections

Dose Limiting Toxicity Evaluation

Evaluation of dose limiting toxicity (DLT) from the start of treatment through Day 28

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of adverse events and other secondary outcomes

12 months

Treatment Details

Interventions

• VG2025 (Virus Therapy)

Trial Overview The trial tests VG2025 alone and combined with Nivolumab in patients with advanced malignant solid tumors. It's a Phase I study where doses are increased gradually to find the maximum safe amount. Patients receive bi-weekly injections directly into the tumor over a four-week period.

Participant Groups

Group I: Monotherapy Arm Experimental Treatment 1 Intervention

This is an open label trial using standard 3+3 design, in up to 24 HSV seropositive subjects. This rule-based design proceeds with cohorts of three patients.

Group II: Combination Arm Experimental Treatment 2 Interventions

The starting dose of VG2025 in the combination cohorts will be a dose of 1.0 x108 PFU for combination cohort 1 on days 1 and 15 of every cycle. Combination cohort 2 will be dosed at 1.0 x108 PFU on Day 1 and either Day 2 or 3 in cycle 1 and 2. Day 1 only in subsequent cycles

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Banner MD Anderson Cancer Center Gilbert, AZ

MD Anderson Houston, TX

Who Is Running the Clinical Trial?

Virogin Biotech Canada Ltd

Lead Sponsor

Trials

2

Recruited

110+

Findings from Research

In a study of 66 patients with advanced non-small cell lung cancer (NSCLC) treated with nivolumab, those with a poor performance status (PS ≥2) had a significantly shorter median overall survival of 3.04 months compared to 10.23 months for those with better performance status (PS ≤1).

Despite similar rates of treatment-related adverse events between the two groups, the findings suggest that performance status is a crucial factor in predicting survival outcomes and should be considered when selecting immunotherapy treatments for lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world experience of nivolumab in the treatment of poor performance status patients with advanced non-small cell lung cancer. Abbas, MN., Klevansky, M., Koczwara, B., et al.[2022]

Nivolumab, an anti-PD-1 monoclonal antibody, has significantly improved treatment outcomes for advanced cancers like lung cancer, renal cancer, and melanoma, promoting long-lasting anti-tumor immunity.

Despite its effectiveness, nivolumab monotherapy fails in 60-70% of patients, but combining it with other therapies, such as chemotherapy or CTLA-4 inhibitors, has been shown to enhance its efficacy and overcome resistance in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination therapy with nivolumab (anti-PD-1 monoclonal antibody): A new era in tumor immunotherapy. Abedi Kiasari, B., Abbasi, A., Ghasemi Darestani, N., et al.[2022]

In a study of 38 advanced NSCLC patients aged 70 and older, Nivolumab demonstrated a median overall survival of 14.85 months and a median progression-free survival of 7.53 months, indicating its efficacy in this older population.

The safety profile of Nivolumab in these older patients was consistent with that observed in the broader population, with no new adverse events reported, suggesting it is a safe treatment option for elderly patients with advanced lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of Nivolumab in older patients with pretreated lung cancer: A subgroup analysis of the Galician lung cancer group. Arias Ron, D., Areses Manrique, MC., Mosquera Martínez, J., et al.[2021]

In a phase I study involving 56 patients with advanced non-small-cell lung cancer, nivolumab combined with platinum-based chemotherapy showed promising efficacy, particularly with a 2-year overall survival rate of 62% for the nivolumab 5 mg/kg plus paclitaxel-carboplatin group.

While the safety profile was generally consistent with expectations, 45% of patients experienced grade 3 or 4 treatment-related adverse events, and 21% discontinued treatment due to these adverse effects, indicating a need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab in Combination With Platinum-Based Doublet Chemotherapy for First-Line Treatment of Advanced Non-Small-Cell Lung Cancer. Rizvi, NA., Hellmann, MD., Brahmer, JR., et al.[2022]

Nivolumab, a PD-1 monoclonal antibody, is an effective first-line treatment for advanced non-small-cell lung cancer (NSCLC) and has become a key option for patients without targetable genetic alterations.

Despite its success, there is a need for reliable biomarkers to predict which patients will respond to PD-1 inhibition, with ongoing research focusing on factors like PD-L1 expression and tumor mutation burden.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect and biomarker of Nivolumab for non-small-cell lung cancer. Wang, L., Zhao, D., Qin, K., et al.[2020]

References

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

The benefit and risk of nivolumab in non-small-cell lung cancer: a single-arm meta-analysis of noncomparative clinical studies and randomized controlled trials. [2019]

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

Nivolumab Monotherapy for First-Line Treatment of Advanced Non-Small-Cell Lung Cancer. [2022]

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

Real-world experience of nivolumab in the treatment of poor performance status patients with advanced non-small cell lung cancer. [2022]

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

An update on the pharmacodynamics, pharmacokinetics, safety and clinical efficacy of nivolumab in the treatment of solid cancers. [2018]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Combination therapy with nivolumab (anti-PD-1 monoclonal antibody): A new era in tumor immunotherapy. [2022]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Efficacy and safety of Nivolumab in older patients with pretreated lung cancer: A subgroup analysis of the Galician lung cancer group. [2021]

7. England pubmed.ncbi.nlm.nih.gov

First-line nivolumab + ipilimumab in advanced NSCLC: CheckMate 227 subpopulation analyses in Asian patients. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Side effects of immune-checkpoint inhibitors: Can multiple side effects be seen in a patient? [2022]

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

Nivolumab-Associated Acute Demyelinating Encephalitis: A Case Report and Literature Review. [2020]

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

Efficacy of Nivolumab and Pembrolizumab in Patients With Advanced Non-Small-Cell Lung Cancer Needing Treatment Interruption Because of Adverse Events: A Retrospective Multicenter Analysis. [2019]

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

Nivolumab in Combination With Platinum-Based Doublet Chemotherapy for First-Line Treatment of Advanced Non-Small-Cell Lung Cancer. [2022]

12. France pubmed.ncbi.nlm.nih.gov

Effect and biomarker of Nivolumab for non-small-cell lung cancer. [2020]

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

Italian Nivolumab Expanded Access Program in Nonsquamous Non-Small Cell Lung Cancer Patients: Results in Never-Smokers and EGFR-Mutant Patients. [2019]