VG2025 + Nivolumab for Advanced Cancer

Recruiting at 1 trial location

Overseen By Mike Teng

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Virogin Biotech Canada Ltd

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

Disqualifiers: CNS malignancy, Heart failure, Autoimmune, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

12 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, VG2025 (an experimental treatment), both alone and in combination with Nivolumab, to assess its safety for individuals with advanced malignant solid tumors. Participants have tumors unresponsive to other treatments and may require a visible or palpable tumor for injection. Those who test positive for Herpes Simplex Virus (HSV) and have had a break from recent cancer treatments might be suitable candidates. The trial aims to determine the appropriate dosage and monitor any side effects of these treatments. As a Phase 1 trial, this research seeks to understand how VG2025 functions in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

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

Research has shown that VG2025 is generally safe when used alone. Studies have found it to be well-tolerated by patients with advanced solid tumors who have already tried other treatments, with most experiencing only mild side effects.

The safety of VG2025 combined with Nivolumab is still under investigation. Nivolumab, already used for various cancers, is usually safe for patients. Previous studies with Nivolumab have shown it can cause some side effects, but these are often manageable. This trial aims to determine if the side effects remain mild when both drugs are used together.

As a Phase 1 trial, the primary focus is on safety. Early results suggest VG2025 alone is well-tolerated, but more information is needed to confirm its safety when combined with Nivolumab. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

VG2025 is unique because it uses a new viral-based approach to target advanced cancer cells. Unlike traditional chemotherapy or radiation, which can affect healthy cells, VG2025 leverages a modified virus to specifically attack cancer cells while sparing normal cells. Researchers are particularly excited about the potential for VG2025 to work in combination with Nivolumab, an immune checkpoint inhibitor, because this combination could enhance the body's immune response against cancer, potentially leading to more effective treatments with fewer side effects.

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

Research has shown that VG2025, which participants in this trial may receive as monotherapy, has helped fight cancer in patients with advanced solid tumors unresponsive to standard treatments. The treatment generally caused few side effects, indicating it was well-tolerated.

In this trial, researchers are also studying VG2025 in combination with Nivolumab. Nivolumab is already known to help people with cancers like lung cancer and melanoma by boosting the immune system. Early studies suggest that combining VG2025 with Nivolumab could enhance these benefits, potentially offering a stronger treatment option for advanced cancers. ^{1 2 4 5 6}

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• VG2025

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.

How Is the Trial Designed?

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

Who Is Running the Clinical Trial?

Virogin Biotech Canada Ltd

Lead Sponsor

Trials

2

Recruited

110+

Published Research Related to This Trial

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]

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]

In a study of 271 advanced non-small-cell lung cancer patients treated with PD-1 antibodies, 42.8% experienced immune-related adverse events (irAEs), which were linked to lower overall survival (OS) rates, particularly in those with severe irAEs like colitis.

Patients who required treatment interruption due to irAEs had significantly lower OS compared to those who continued therapy, highlighting the need for better management strategies for irAEs to improve patient outcomes.

NCBI (Pubmed)

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. Ksienski, D., Wai, ES., Croteau, N., et al.[2019]

In a study of 1588 patients with nonsquamous NSCLC, nivolumab showed a higher objective response rate in patients with wild-type EGFR compared to those with EGFR-mutant tumors (19.6% vs. 8.8%), indicating that EGFR status influences treatment efficacy.

Never-smokers had a lower response rate to nivolumab (9.2%) compared to former and current smokers (21.5%), but among never-smokers, those with wild-type EGFR had a significantly better response (11.0%) than those with mutant EGFR (1.9%).

NCBI (Pubmed)

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. Garassino, MC., Gelibter, AJ., Grossi, F., et al.[2019]

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]

Nivolumab, a PD-1 inhibitor, has demonstrated significant safety and efficacy in treating various advanced solid tumors, including melanoma and lung cancer, based on multiple high-level studies.

Future research should aim to identify predictive biomarkers for treatment response and explore the potential of combining nivolumab with other therapies, as well as determining the best treatment strategies and duration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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

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]

A case study of a 59-year-old woman with treatment-resistant laryngeal cancer revealed that nivolumab, an immunotherapy drug, can cause severe central nervous system (CNS) toxicities, specifically acute demyelinating encephalitis, which is rarely reported in the literature.

The patient's symptoms improved significantly after discontinuing nivolumab and receiving high-dose steroids and immunoglobulin therapy, suggesting that CNS toxicity from immune checkpoint inhibitors may be reversible with prompt treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab-Associated Acute Demyelinating Encephalitis: A Case Report and Literature Review. Zafar, Z., Vogler, C., Hudali, T., et al.[2020]

Nivolumab, an immune checkpoint inhibitor, showed a tolerable safety profile in 52 patients with advanced non-small-cell lung cancer (NSCLC), with 71% experiencing treatment-related adverse events, primarily fatigue and rash.

The treatment resulted in a confirmed objective response rate of 23%, with some patients achieving ongoing complete responses, and a median overall survival of 19.4 months, indicating its potential as an effective first-line therapy for advanced NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab Monotherapy for First-Line Treatment of Advanced Non-Small-Cell Lung Cancer. Gettinger, S., Rizvi, NA., Chow, LQ., et al.[2022]

Nivolumab, a PD-1 receptor inhibitor, shows an objective response rate of 18% and a 1-year overall survival rate of 45% in patients with advanced non-small-cell lung cancer, based on a meta-analysis of 20 studies involving 3404 patients.

The presence of PD-L1 expression in patients is associated with a better response to nivolumab, indicating that PD-L1 status can help predict treatment outcomes.

NCBI (Pubmed)

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. Zhao, B., Zhang, W., Yu, D., et al.[2019]

In the Asian subpopulation with advanced non-small cell lung cancer (NSCLC) and PD-L1 expression ≥1%, patients treated with nivolumab plus ipilimumab showed significantly improved overall survival (OS) and progression-free survival (PFS) compared to those receiving chemotherapy, with a 3-year OS rate of 53% versus 37%.

The safety profile of nivolumab plus ipilimumab was manageable, with grade 3-4 treatment-related adverse events occurring in 40% of patients, similar to the 36% in the chemotherapy group, indicating no new safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line nivolumab + ipilimumab in advanced NSCLC: CheckMate 227 subpopulation analyses in Asian patients. O'Byrne, KJ., Lee, KH., Kim, SW., et al.[2022]

Nivolumab, a monoclonal antibody used to treat recurrent renal cell carcinoma, can cause significant immune-related adverse events, such as hepatitis and adrenalitis, as seen in a case study of a 66-year-old male patient.

Prompt recognition and management of these side effects are crucial; in this case, the patient's hepatitis improved with methylprednisolone, and adrenalitis was treated with fludrocortisone, leading to normalization of symptoms and electrolyte levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Side effects of immune-checkpoint inhibitors: Can multiple side effects be seen in a patient? Özyurt, E., Özçelik, S., Sürmeli, H., 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]

Citations

1. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)02572-9/fulltext

994MO The updated report of phase I trial of VG2025, a ... Intratumoral injection of VG2025 monotherapy has demonstrated anti-cancer activity with a well-tolerant safety profile in pts progressed after standard of ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.2580

The initial report of phase I trial of VG2025, a non- ... Here we report a first-in-human, open label, study to evaluate the safety, pharmacokinetics (PK), and biologic effects of VG2025 in patients (pts) with ...

3. annalsofoncology.org annalsofoncology.org/article/S0923-7534(23)04424-1/fulltext

83P The updated report of phase I trial of VG2025, a non- ... Monotherapy with VG2025 demonstrated activity with a well-tolerant safety profile in pts with advanced solid tumors that progressed after standard of care ...

4. withpower.com withpower.com/trial/phase-1-neoplasms-5-2022-5923b

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 ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05266612

NCT05266612 | Phase I Study VG2025 as a Single Agent ... This is a Phase 1, open-label, dose-escalation trial using standard 3+3 dose-escalation design in patients with advanced malignant solid tumors.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05477849

NCT05477849 | A Clinical Study to Evaluate the Safety, ... This is an open label study to determine the safety and tolerability of VG2025, and recommended dose of VG2025 for Phase II trials. Detailed Description. This ...