Vusolimogene + Pembrolizumab for Angiosarcoma

Overseen By Lisa Tan

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Varun Monga, MBBS

Must not be taking: Antivirals, Immunosuppressants, others

Disqualifiers: Hepatitis, HIV, Pneumonitis, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 3

Duration: Up to 2 years

18 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines a new treatment combination for angiosarcoma, a rare cancer affecting the lining of blood vessels. Researchers aim to assess the safety and efficacy of combining Vusolimogene Oderparepvec (an experimental treatment) with pembrolizumab for patients whose cancer has worsened after previous treatments. Individuals with advanced, inoperable angiosarcoma who have not responded to other immunotherapy treatments may 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 currently on antiviral drug therapy or have had systemic anticancer therapy within 4 weeks before enrollment. It's best to discuss your specific medications with the trial team.

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

Previous studies found the combination of Vusolimogene Oderparepvec (VO) and nivolumab to be safe for people with advanced melanoma. The FDA raised no safety concerns about VO during its review, suggesting that VO might be well-tolerated in humans.

Research has shown that pembrolizumab, studied in other cancers like angiosarcoma, has helped patients live longer without disease progression. Safety data from various studies indicate that pembrolizumab is generally well-tolerated.

These findings suggest that using VO and pembrolizumab together might be safe. However, each treatment can have side effects, so participants should discuss potential risks with their doctors. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for angiosarcoma, which typically involve chemotherapy and radiation, the combination of Vusolimogene Oderparepvec (VO) and pembrolizumab offers a novel approach. Researchers are excited because VO is an oncolytic virus designed to selectively infect and kill cancer cells, potentially boosting the immune response against the tumor. Pembrolizumab, an immune checkpoint inhibitor, works by enhancing the body's immune system to attack cancer cells more effectively. This dual-action strategy is promising because it not only directly targets cancer cells with VO but also empowers the immune system with pembrolizumab, potentially leading to better outcomes than current treatments.

What evidence suggests that this combination treatment could be effective for angiosarcoma?

Research has shown that combining vusolimogene oderparepvec (VO) and pembrolizumab may effectively treat angiosarcoma. In this trial, all participants will receive both VO and pembrolizumab. Previous studies have found that pembrolizumab, which helps the immune system fight cancer, can slow the disease in angiosarcoma patients, making it a useful treatment. VO, a type of virus therapy, has significantly shrunk tumors, with effects lasting over 21 months for many patients. This combination is believed to boost the body's immune response against tumors. Early results in similar cancer types support the potential success of this combination for treating angiosarcoma. ^{2 4 6 7 8}

Who Is on the Research Team?

Varun Monga, MBBS

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

This trial is for individuals with advanced angiosarcoma, a type of cancer that affects the lining of blood vessels. Participants must have seen their disease progress after previous immunotherapy treatments.

Inclusion Criteria

Life expectancy of at least 3 months, in the opinion of the treating investigator

My cancer progressed after first-line treatment with taxane or anthracycline.

My cancer can be measured and has grown in previously treated areas.

Exclusion Criteria

I had radiotherapy over 2 weeks ago and have no side effects needing steroids.

Is a person deprived of their liberty by a judicial or administrative decision, or an adult person subject to a legal protection measure

I have been treated with a virus-based cancer therapy before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Lead-in

To assess the safety and tolerability of VO in combination with pembrolizumab

Up to 1 year

Treatment

Participants receive VO and pembrolizumab, with VO administered every 3 weeks for 7 cycles and pembrolizumab every 3 weeks for 8 cycles, potentially altering to every 6 weeks thereafter

Up to 2 years

Every 3 weeks for 8 cycles, then every 6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, with tumor response assessments approximately every 12 weeks and survival follow-up every 6 months

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab
• Vusolimogene Oderparepvec (VO)

Trial Overview

The study tests a new treatment combining Intratumoral Vusolimogene Oderparepvec (VO) directly injected into the tumor and Pembrolizumab given systemically. It's an open-label study, meaning both researchers and participants know what treatments are being used.

How Is the Trial Designed?

Group I: Treatment (Vusolimogene Oderparepvec (VO), Pembrolizumab) Experimental Treatment 2 Interventions

All participants receive a single dose of VO on Day -14. On Cycle 1 Day 1 (C1D1), participants receive second dose of VO, and subsequent doses occur every 3 weeks for 7 cycles in combination with 200 mg pembrolizumab every 3 weeks for 8 cycles starting C1D1. After 8 cycles of pembrolizumab, participants may have the pembrolizumab dose schedule altered to a single 400 mg dose every 6 weeks, and treatment with pembrolizumab may continue for up to 2 years after starting first dose on C1D1. Participants may receive up to eight additional doses of VO after progression for a total of 16 dosing days. Safety follow up visits occur 30 and 90 days after last dose of either treatment (whichever drug was taken last) or after the participant has taken 2 years of pembrolizumab as a part of this study.

Who Is Running the Clinical Trial?

Varun Monga, MBBS

Lead Sponsor

Trials

1

Recruited

20+

Replimune Inc.

Industry Sponsor

Trials

16

Recruited

1,700+

Published Research Related to This Trial

A systematic review of four trials involving 3425 patients found that lower doses of pembrolizumab (2 mg/kg every 3 weeks) are equally effective as higher doses (10 mg/kg) in treating advanced melanoma and non-small-cell lung cancer (NSCLC).

The safety profile of pembrolizumab was similar across different doses, suggesting that the lower dose may be sufficient for routine treatment without compromising efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of efficacy and safety of different pembrolizumab dose/schedules in treatment of non-small-cell lung cancer and melanoma: a systematic review. Abdel-Rahman, O.[2018]

In a phase 2 study involving 86 patients with advanced soft-tissue or bone sarcoma, pembrolizumab demonstrated some efficacy, particularly in undifferentiated pleomorphic sarcoma (40% response rate) and dedifferentiated liposarcoma (20% response rate), although the overall response rate did not meet the primary endpoint.

The treatment was associated with some serious adverse events, including immune-related conditions like adrenal insufficiency and pneumonitis, highlighting the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in advanced soft-tissue sarcoma and bone sarcoma (SARC028): a multicentre, two-cohort, single-arm, open-label, phase 2 trial. Tawbi, HA., Burgess, M., Bolejack, V., et al.[2022]

Pembrolizumab, an anti-PD-1 antibody, has been approved for treating unresectable or metastatic melanoma, especially in patients who have progressed after ipilimumab treatment, marking a significant advancement in immuno-oncology.

The drug has also received breakthrough status for treating non-small cell lung cancer (NSCLC) that is EGFR mutation-negative and ALK rearrangement-negative, indicating its broad potential in cancer therapy, with ongoing trials to explore its use in various tumor types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab. Khoja, L., Butler, MO., Kang, SP., et al.[2022]

Pembrolizumab, an immune checkpoint inhibitor used for treating metastatic non-small-cell lung cancer, can cause serious side effects such as myocarditis, as demonstrated in a case where a patient developed severe cardiac dysfunction after two treatment cycles.

The patient responded well to corticosteroids and heart failure therapy, highlighting the importance of monitoring for autoimmune adverse events in patients receiving pembrolizumab, as these can significantly impact clinical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New drugs and new toxicities: pembrolizumab-induced myocarditis. Inayat, F., Masab, M., Gupta, S., et al.[2020]

In a phase 2 trial involving 33 patients with advanced sarcomas, the combination of axitinib and pembrolizumab showed a promising 3-month progression-free survival rate of 65.6%, with even higher rates of 72.7% for patients with alveolar soft-part sarcoma (ASPS).

The treatment was associated with manageable side effects, with 21% of patients experiencing serious adverse events, but no treatment-related deaths, indicating a favorable safety profile for further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Axitinib plus pembrolizumab in patients with advanced sarcomas including alveolar soft-part sarcoma: a single-centre, single-arm, phase 2 trial. Wilky, BA., Trucco, MM., Subhawong, TK., et al.[2020]

Pembrolizumab is an effective monoclonal antibody that targets the PD-1 immune checkpoint, helping to restore T cell anti-tumor responses, and is administered at a dose of 200 mg every 3 weeks until disease progression or for up to 24 months.

It has received approval for treating various cancers, including melanomas and non-small cell lung cancers, particularly in tumors that are hypermutated or express PD-L1, but ongoing research aims to expand its use to less immunogenic tumor types through combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical utility of pembrolizumab in the management of advanced solid tumors: an evidence-based review on the emerging new data. du Rusquec, P., de Calbiac, O., Robert, M., et al.[2023]

The combination of pembrolizumab, an immune checkpoint inhibitor, with the oncolytic virus talimogene laherparepvec has shown effectiveness in treating sarcomas, a type of cancer.

This study suggests a promising therapeutic strategy by leveraging both immune response and direct tumor lysis to improve treatment outcomes for patients with sarcomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Talimogene Laherparepvec plus Pembrolizumab Is Effective in Sarcomas. [2020]

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]

Pembrolizumab is a safe and effective immune checkpoint inhibitor that targets the PD-1 receptor, currently approved for treating advanced melanoma and metastatic non-small cell lung cancer (NSCLC).

Ongoing studies are exploring the potential of pembrolizumab in combination with other treatments for lung cancer and other cancer types, while also investigating biomarkers that may predict patient response to this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of PD-L1 positive advanced or metastatic non-small cell lung cancer. Dang, TO., Ogunniyi, A., Barbee, MS., et al.[2020]

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