Voyager V1 + Cemiplimab for Melanoma

Recruiting at 10 trial locations

Overseen By Jennifer boughton

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Vyriad, Inc.

Must not be taking: Small molecule inhibitors

Disqualifiers: HIV, HBV, HCV, TB, 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: 3

Duration: Variable (up to 24 months)

87 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments: VV1 (an experimental treatment) and cemiplimab (an immune checkpoint inhibitor). The goal is to determine their effectiveness in shrinking tumors and their safety for patients with certain progressing cancers. The focus is on colorectal, head and neck carcinoma, and melanoma cancers that have not responded well to previous treatments. Ideal participants include those with advanced melanoma that has worsened despite earlier treatment with immune checkpoint inhibitors, such as anti-PD-1 therapy. The trial seeks individuals with tumors that can be directly injected with the treatment. As a Phase 2 trial, the research measures how well the treatment works in an initial, smaller group of people.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, there are specific timeframes for stopping certain therapies before starting the trial: small molecule inhibitors and investigational agents must be stopped 2 weeks or 5 half-lives before, chemotherapy and similar therapies 3 weeks or 5 half-lives before, and radioimmunoconjugates 6 weeks or 5 half-lives before. It's best to discuss your current medications with the trial team.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, there are specific timeframes for stopping certain therapies before starting the trial, such as small molecule inhibitors and chemotherapy. It's best to discuss your current medications with the trial team to get personalized advice.

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

Studies have shown that cemiplimab is already approved for treating certain skin and lung cancers, providing a good understanding of its safety. Most people tolerate it well, though some may experience side effects like tiredness or a rash.

For Voyager V1 (VV1), previous studies with patients who have advanced solid tumors assessed its safety and tolerability. These studies identified any serious side effects to ensure the treatment's safety.

As a Phase 2 study, this stage follows earlier phases where basic safety was tested. This phase focuses on the treatment's effectiveness and continues to monitor its safety. So far, the combination of VV1 and cemiplimab has been deemed safe enough to proceed. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about VV1 and cemiplimab for melanoma because they offer a unique combination approach. Unlike standard treatments such as surgery, radiation, and checkpoint inhibitors like pembrolizumab, this treatment combines intratumoral VV1 with intravenous cemiplimab. VV1 is an oncolytic virus that selectively infects and destroys cancer cells, potentially enhancing the immune response against tumors. Cemiplimab is an immune checkpoint inhibitor that helps the immune system recognize and attack cancer cells. This dual-action approach may boost the immune system's ability to target and eliminate melanoma cells more effectively than current treatments alone.

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

Studies have shown that cemiplimab, a medicine that aids the immune system in fighting cancer, effectively treats various cancers, such as lung and basal cell skin cancers. Research indicates that combining cemiplimab with Voyager V1 (VV1), a virus designed to attack cancer cells, may enhance its effectiveness. Early findings suggest this combination helps the immune system combat cancer more efficiently. This trial will focus on the combination of cemiplimab and VV1 to determine its potential in reducing tumor growth specifically in melanoma. Previous patients have shown promising responses to similar treatments, offering hope for those with cancers not responding to other therapies. ^{1 5 6 7 8}

Who Is on the Research Team?

Alice Bexon, MD

Principal Investigator

CMO

Stephen J Russell, MD, Ph.D.

Principal Investigator

Clinical Lead

Are You a Good Fit for This Trial?

Adults with certain progressing cancers (oral, head and neck carcinoma, melanoma, colorectal) previously treated with CPI can join. They must have a tumor lesion suitable for injection/biopsy, measurable disease, good performance status (ECOG 0 or 1), over three months life expectancy, and proper organ function. Exclusions include ocular/mucosal/acral melanoma patients; active HBV/HCV/TB infections; serious health risks like uncontrolled hypertension/diabetes; recent use of certain drugs; heart issues; autoimmune diseases except controlled hypothyroidism/type 1 diabetes; immunosuppression conditions.

Inclusion Criteria

My cancer can be measured and has at least one lesion that can be injected.

I have a tumor that can be injected and biopsied, and it hasn't been treated with radiation.

My recent tests show my organs are working well.

Exclusion Criteria

I do not have any severe autoimmune diseases except well-controlled hypothyroidism or type 1 diabetes.

I am currently infected with hepatitis B.

I stopped taking small molecule inhibitors or other trial drugs less than 2 weeks ago.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive Voyager V1 as a direct to tumor injection and cemiplimab via IV infusion every 3 weeks until lack of clinical benefit or limiting toxicity

Variable (up to 24 months)

Every 3 weeks

Efficacy Evaluation

Efficacy evaluations are conducted every 6 weeks to assess objective response rate

Every 6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cemiplimab
• VV1

Trial Overview The trial is testing the combination of VV1 and Cemiplimab to see how well they work together against specific types of cancer that are not responding to previous treatments. It's in Phase 2 which means it's checking both effectiveness and safety in treating these cancers.

How Is the Trial Designed?

Group I: Melanoma intratumoral Experimental Treatment 2 Interventions

Melanoma, IT VV1 + IV cemiplimab Patients will receive both treatments on Day 1 and every 3 weeks thereafter until lack of clinical benefit or limiting toxicity. VV1 or cemiplimab can continue after the first dose in combination or as a single agent treatment in subsequent doses.

Group II: Head and Neck SCC intratumoral Experimental Treatment 2 Interventions

HNSCC, IT VV1 + IV cemiplimab, Patients will receive both treatments on Day 1 and every 3 weeks thereafter until lack of clinical benefit or limiting toxicity. VV1 or cemiplimab can continue after the first dose in combination or as a single agent treatment in subsequent doses.

Group III: Colo-rectal Carcinoma intratumoral (Arm closed) Experimental Treatment 2 Interventions

(CLOSED) IT VV1 + IV cemiplimab, Patients will receive both treatments on Day 1 and every 3 weeks thereafter until lack of clinical benefit or limiting toxicity. VV1 or cemiplimab can continue after the first dose in combination or as a single agent treatment in subsequent doses.

Cemiplimab is already approved in European Union, United States, Canada, Brazil for the following indications:

Approved in European Union as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)
• Non-small cell lung cancer (NSCLC)

Approved in United States as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)
• Basal cell carcinoma (BCC)
• Non-small cell lung cancer (NSCLC)

Approved in Canada as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)
• Non-small cell lung cancer (NSCLC)

Approved in Brazil as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)

Who Is Running the Clinical Trial?

Vyriad, Inc.

Lead Sponsor

Trials

6

Recruited

290+

Regeneron Pharmaceuticals

Industry Sponsor

Trials

690

Recruited

948,000+

Founded

1988

Headquarters

Tarrytown, USA

Known For

Precision medicine

Top Products

Dupixent, EYLEA, Libtayo, Praluent

Leonard Schleifer

Regeneron Pharmaceuticals

Chief Executive Officer since 1988

MD and PhD in Medicine

George Yancopoulos

Regeneron Pharmaceuticals

Chief Medical Officer since 1997

MD from Harvard Medical School

Published Research Related to This Trial

The combination of relatlimab and nivolumab has shown promising efficacy in advanced melanoma, as highlighted by the phase II-III RELATIVITY-047 trial, suggesting it could be a strong alternative to the standard ipilimumab-nivolumab treatment.

However, the trial also revealed some rare but significant immune-related adverse events, indicating the need for careful monitoring and pharmacovigilance to ensure patient safety in real-world applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relatlimab and nivolumab in untreated advanced melanoma: insight into RELATIVITY. Raschi, E., Comito, F., Massari, F., et al.[2023]

The combination of nivolumab and ipilimumab, two immune checkpoint inhibitors, is a promising treatment for advanced melanoma, enhancing the body's immune response against the cancer.

Adding denosumab to this treatment may further improve anti-tumor effects by counteracting the immunosuppressive environment created by CD8+ T cells, as suggested by recent reports.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful Treatment of Multiple Metastatic Melanoma with Nivolumab, Ipilimumab plus Denosumab Combined Therapy. Yoshida, S., Fujimura, T., Kambayashi, Y., et al.[2020]

In a study of 56 melanoma patients, those who received prior treatment with pegylated interferon alpha (PEG-IFN-α) showed significantly improved efficacy from subsequent adjuvant pembrolizumab therapy, with a hazard ratio of 0.37 indicating a lower risk of recurrence.

Patients treated with prior PEG-IFN-α had a longer recurrence-free survival (RFS) of 8.5 months compared to 4.5 months for those without prior treatment, suggesting that PEG-IFN-α enhances the effectiveness of PD-1 blockade in melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prior Therapy With Pegylated-Interferon Alfa-2b Improves the Efficacy of Adjuvant Pembrolizumab in Resectable Advanced Melanoma. Jia, DD., Niu, Y., Zhu, H., et al.[2021]

In a study of 40 patients with metastatic melanoma who progressed after anti-PD-1 therapy, 10% achieved an objective response to subsequent treatment with ipilimumab, and 8% experienced prolonged stable disease for over 6 months.

However, 35% of patients developed severe immune-related toxicities, with the most common being diarrhea, and 7% experienced life-threatening pneumonitis, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and toxicity of treatment with the anti-CTLA-4 antibody ipilimumab in patients with metastatic melanoma after prior anti-PD-1 therapy. Bowyer, S., Prithviraj, P., Lorigan, P., et al.[2021]

In a phase 2 study of 185 patients with advanced BRAFV600-mutated melanoma, switching from targeted therapy (vemurafenib + cobimetinib) to atezolizumab after 3 months resulted in significantly shorter progression-free survival (PFS) compared to continuing targeted therapy (13.9 months vs. 5.9 months).

Despite the rapid loss of tumor control with the switch to atezolizumab, there was a numerical overall survival (OS) benefit at 2 years for patients who switched (67% vs. 58% for continued targeted therapy), suggesting potential long-term advantages of the immunotherapy approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early switch from run-in treatment with vemurafenib plus cobimetinib to atezolizumab after 3 months leads to rapid loss of tumour control in patients with advanced BRAFV600-positive melanoma: The ImmunoCobiVem phase 2 randomised trial. Livingstone, E., Gogas, H., Kandolf-Sekulovic, L., et al.[2023]

Pembrolizumab is a monoclonal antibody that effectively blocks the PD-1 receptor on T cells, enhancing their ability to attack cancer cells, particularly in melanoma patients.

In a Phase I study involving 411 patients, pembrolizumab demonstrated high durable response rates with minimal toxicity, indicating its potential as a safe and effective treatment option for melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. Hersey, P., Gowrishankar, K.[2017]

A 68-year-old man developed autoimmune limbic encephalitis after nine cycles of nivolumab treatment, highlighting the potential for serious neurological immune-related adverse events (irAEs) associated with this PD-1 inhibitor.

The patient responded well to high-dose corticosteroids but experienced a relapse upon tapering, emphasizing the need for careful monitoring and management of neurological symptoms in patients receiving nivolumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Very high-dose methylprednisolone for treatment of nivolumab-induced limbic encephalitis: A case report. Taillefer, VT., Pigeon, M., Chen, M., et al.[2022]

Anti-PD1 therapies, such as pembrolizumab and nivolumab, have shown response rates of 30-40% in patients with metastatic melanoma, providing a significant overall survival benefit compared to traditional chemotherapy and the earlier drug ipilimumab, which had a lower response rate and higher toxicity.

The combination of ipilimumab and nivolumab has been approved and demonstrates improved response rates of 50-57%, but it also comes with a higher risk of serious adverse events, highlighting the need for careful consideration in treatment planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Not Available]. Mateus, C., Libenciuc, C., Robert, C.[2018]

Pembrolizumab, an anti-PD-1 antibody, has shown significant efficacy in treating advanced melanoma, demonstrating superior progression-free survival compared to chemotherapy in Phase II trials and improved overall survival in Phase III trials.

The treatment is generally well tolerated with a favorable safety profile, though common side effects include fatigue and rash, while less frequent but serious immune-related adverse events can occur.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in the management of metastatic melanoma. Spain, L., Younger, E., Hatipoglu, E., et al.[2020]

In a study of 88 advanced melanoma patients treated with pembrolizumab, 81.8% experienced any-grade toxicities, with skin and gastrointestinal issues being the most common side effects.

Despite the high incidence of side effects, pembrolizumab was found to be well tolerated in real-world settings, and severe toxicities were manageable with systemic steroids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world experience with pembrolizumab toxicities in advanced melanoma patients: a single-center experience in the UK. So, AC., Board, RE.[2022]

In a study of 2834 melanoma patients treated with immune checkpoint inhibitors, 82 developed rare immune-related adverse events (RirAEs), with a higher incidence in those receiving combination therapy (4.6%) compared to anti-PD-1/L1 agents (2.8%).

Most RirAEs were of moderate severity (grade 2 and 3), and while steroid re-escalation and additional immunosuppression were often needed, fatal events were relatively rare, indicating that while RirAEs can occur, they are manageable in most cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rare immune-related adverse events in patients with melanoma: incidence, spectrum, and clinical presentations. Park, BC., Narayanan, S., Gavraldis, A., et al.[2023]

In a study involving 43 patients with advanced melanoma, the combination of pembrolizumab and pegylated interferon (PEG-IFN) showed a promising objective response rate of 60.5%, indicating significant efficacy in treating PD-1-naïve patients.

The treatment was associated with an acceptable safety profile, with 48.8% of patients experiencing grade 3/4 treatment-related adverse events, and a median progression-free survival of 11 months, suggesting that this combination therapy warrants further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase Ib/II Study of Pembrolizumab and Pegylated-Interferon Alfa-2b in Advanced Melanoma. Davar, D., Wang, H., Chauvin, JM., et al.[2021]

Nivolumab significantly improved one-year survival rates in patients with inoperable or metastatic BRAF V600-negative melanoma compared to dacarbazine (73% vs. 42%), indicating its efficacy as a first-line treatment option.

While nivolumab shows promise for treatment-naive patients, it does not demonstrate a clear advantage over other treatments for patients who have already received therapy, and it carries a risk of serious immunological side effects in 9% of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab (OPDIVOO) BRAF V600 mutation-negative metastatic or inoperable melanoma: survival advantage. [2019]

Nivolumab, an immune checkpoint inhibitor, shows strong antitumor activity but is associated with immune-related adverse events that can affect patient safety and treatment continuation, necessitating careful monitoring.

Long-term safety data, including a 5-year follow-up, suggests that nivolumab can be safely administered to various challenging patient subgroups, but identifying biomarkers for severe toxicity could improve patient selection for this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An update on the safety of nivolumab for the treatment of advanced melanoma. Czarnecka, AM., Rutkowski, P.[2021]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.TPS9595

Optimization of Voyager V1 (VV1) oncolytic virus systemic ... We are exploring ways to optimize VV1 efficacy in combination with cemiplimab, an anti-PD1 antibody approved for lung, basal and squamous cell skin cancers.

2. vyriad.com vyriad.com/newsevents/vyriad-announces-initiation-of-phase-2-trial-in-multiple-cancer-indications/

Vyriad Announces Initiation of Phase 2 Trial in Multiple ... The study will evaluate overall patient responses to the treatment, as well as safety, tolerability, pharmacodynamic and pharmacokinetic data.

3. mayo.edu mayo.edu/research/clinical-trials/cls-20484358

Phase 2 Trial of Voyager V1 in Combination With ... The purpose of this study is to determine the preliminary anti-tumor activity and confirm the safety of VV1 in combination with Cemiplimab. The ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S1044532325000685

Latest insights into oncolytic viro-immunotherapy with ... Clinical trial NCT04291105 evaluates the combination of Voyager-V1 with cemiplimab to treat melanoma, head and neck squamous cell carcinoma, and CRC. Cemiplimab ...

5. researchgate.net researchgate.net/publication/367697432_Optimization_of_Voyager_V1_VV1_oncolytic_virus_systemic_delivery_in_combination_with_cemiplimab_and_ipilimumab_in_patients_with_melanoma_and_non-small_cell_lung_cancer_NSCLC

Optimization of Voyager V1 (VV1) oncolytic virus systemic ... We are exploring ways to optimize VV1 efficacy in combination with cemiplimab, an anti-PD1 antibody approved for lung, basal and squamous cell ...

6. clinicaltrials.regeneron.com clinicaltrials.regeneron.com/clinical-trials/a0Mdy0000001C5aEAE/nct04291105

Phase 2 Trial of Voyager V1 in Combination With Cemiplimab ... This is a Phase 2 study designed to determine the preliminary anti-tumor activity and confirm the safety of VV1 in combination with cemiplimab.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12142144/

Phase 1, open-label, multicenter, dose escalation safety ... This study was designed to evaluate the safety, tolerability, and efficacy of OVV-01 in patients with advanced solid tumors.

8. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT04291105/

Clinical Trial: NCT04291105 This is a Phase 2 study designed to determine the preliminary anti-tumor activity and confirm the safety of VV1 in combination with cemiplimab.