Talimogene Laherparepvec for Soft Tissue Sarcoma

Overseen By John Rieth, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: John Rieth

Must not be taking: Anti-herpetics, Anticoagulants

Disqualifiers: Immunodeficiency, Autoimmune disease, Hepatitis, others

Stay on Your Current Meds You can continue your current medications while participating

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Concurrent with radiation until surgery

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for individuals with certain types of soft tissue sarcoma, a cancer that forms in connective tissues. The focus is on using talimogene laherparepvec, an experimental virus therapy, combined with radiation therapy before surgery. The aim is to determine if this combination can shrink tumors enough for successful removal. Suitable candidates for this trial have large, advanced sarcomas that are difficult to remove with surgery alone and have not previously received treatments like talimogene laherparepvec or radiation on the same tumor. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group of participants.

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

The trial does not specify if you need to stop taking your current medications, but you cannot be on anti-herpetic drugs or therapeutic anticoagulants like warfarin. If you're on low molecular weight heparin, you may need to adjust the timing of your dose.

Is there any evidence suggesting that talimogene laherparepvec and neoadjuvant radiation are likely to be safe?

Research shows that talimogene laherparepvec, or T-VEC, is generally safe for people. Prospective participants should know that earlier studies have examined its safety. One study used T-VEC with radiation therapy to observe patient reactions. The results indicated that most people tolerated the treatment without major issues.

While side effects can occur, they are usually mild. Common side effects include flu-like symptoms such as fatigue or fever. These are generally manageable and short-lived. Although no treatment is without risk, current evidence suggests that T-VEC is quite safe for similar conditions. It is crucial to discuss potential risks and benefits with healthcare professionals before joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for soft tissue sarcoma?

Unlike the standard treatments for soft tissue sarcoma, which often involve chemotherapy and radiation, Talimogene Laherparepvec is unique because it uses a modified virus to target and destroy cancer cells. This treatment is designed to be injected directly into the tumor, which allows it to work from the inside out, potentially sparing healthy tissues from damage. Researchers are excited about Talimogene Laherparepvec because its mechanism of action could lead to fewer side effects and offer a more targeted approach to eradicating cancer cells, which might improve the overall effectiveness compared to traditional therapies.

What evidence suggests that talimogene laherparepvec might be an effective treatment for soft tissue sarcoma?

In this trial, participants will receive a combination of talimogene laherparepvec (TVEC) and neoadjuvant radiation therapy. Research has shown that TVEC may help treat certain cancers. In past studies, patients with advanced sarcomas who received TVEC along with other treatments experienced a significant reduction in tumor size. Specifically, when combined with radiation therapy, TVEC helped shrink tumors before surgery. This suggests that TVEC might effectively target and reduce tumors in some soft tissue sarcoma cases. Overall, these findings indicate that TVEC could improve outcomes for patients with locally advanced soft tissue sarcoma. ^{2 4 5 6 7}

Who Is on the Research Team?

John Rieth, MD

Principal Investigator

University of Iowa

Are You a Good Fit for This Trial?

Adults (18+) with certain types of large, locally advanced soft tissue sarcomas that can't be surgically removed with clear margins and are suitable for radiation. Participants must have finished any previous cancer treatments at least a year prior to joining the trial, not have active infections like herpes or hepatitis, no autoimmune diseases, not be pregnant or breastfeeding, and agree to use effective contraception.

Inclusion Criteria

My disease can be treated with injections guided by sight or ultrasound.

Subject has provided informed consent

I am fully active and can carry on all my pre-disease activities without restriction.

Exclusion Criteria

I have active herpes skin sores.

I have a sarcoma linked to an immune deficiency like HIV or after an organ transplant.

History of prior or current autoimmune disease

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Participants receive neoadjuvant radiation therapy

4-6 weeks

Weekly visits for radiation therapy

Treatment

Weekly intratumoral injections of talimogene laherparepvec until surgery

Concurrent with radiation until surgery

Weekly visits for injections

Surgery

Surgery performed 4-6 weeks after the end of radiation therapy

1 week

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-6 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Neoadjuvant Radiation
• Talimogene Laherparepvec

Trial Overview The study is testing the combination of an experimental drug called Talimogene Laherparepvec injected directly into the tumor along with standard preoperative external beam radiation therapy. The goal is to see if this combo is more effective in treating soft tissue sarcoma than current methods.

How Is the Trial Designed?

Group I: Expansion Pilot Experimental Treatment 3 Interventions

Patients will be treated with neoadjuvant radiation and weekly intratumoral injections of talimogene laherparepvec. Weekly injections of talimogene laherparepvec will be continued until surgery. Surgery will be performed 4-6 weeks from the end of radiation therapy to allow for resolution of acute toxicities per current standard of care

Talimogene Laherparepvec is already approved in United States, European Union for the following indications:

Approved in United States as Imlygic for:

• Melanoma lesions in the skin and lymph nodes

Approved in European Union as Imlygic for:

• Unresectable cutaneous, subcutaneous, and nodal lesions in patients with recurrent melanoma

Who Is Running the Clinical Trial?

John Rieth

Lead Sponsor

Trials

4

Recruited

70+

Amgen

Industry Sponsor

Trials

1,508

Recruited

1,433,000+

Founded

1980

Headquarters

Thousand Oaks, USA

Known For

Human Therapeutics

Top Products

Enbrel, Prolia, Neulasta, Otezla

Robert A. Bradway

Amgen

Chief Executive Officer since 2012

MBA from Harvard Business School

Paul Burton

Amgen

Chief Medical Officer since 2023

MD from University of London, PhD in Molecular and Cellular Biology from Imperial College London

Published Research Related to This Trial

Talimogene laherparepvec (T-VEC) is an effective treatment for advanced melanoma, showing an overall response rate of 26% and significantly improving the durable response rate compared to granulocyte-macrophage colony-stimulating factor (16.3% vs 2.1%).

T-VEC is generally well tolerated with mild to moderate adverse effects, and while it does not significantly improve median overall survival compared to other treatments, it is the first approved oncolytic virus for local treatment of melanoma lesions, with ongoing trials exploring its use in combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Talimogene Laherparepvec: An Oncolytic Virus Therapy for Melanoma. Corrigan, PA., Beaulieu, C., Patel, RB., et al.[2018]

In a study involving 76 patients treated with talimogene laherparepvec (T-VEC) for unresectable melanoma, 20% achieved complete response with no remaining injectable lesions, indicating its efficacy in clinical practice.

T-VEC was well tolerated, with flu-like symptoms being the most common side effect in only 10.5% of patients, and no serious infections reported, highlighting its safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Observational study of talimogene laherparepvec use for melanoma in clinical practice in the United States (COSMUS-1). Perez, MC., Zager, JS., Amatruda, T., et al.[2022]

In a phase 2 study involving 60 patients with advanced melanoma, talimogene laherparepvec (T-VEC) was found to be safely administered with minimal risk of transmission to close contacts when proper occlusive dressings were used.

T-VEC DNA was primarily detected in injected lesions and blood during treatment, but only a small percentage showed infectivity, indicating that while the virus is present, the risk of spreading it to others is low.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biodistribution, shedding, and transmissibility of the oncolytic virus talimogene laherparepvec in patients with melanoma. Andtbacka, RHI., Amatruda, T., Nemunaitis, J., et al.[2020]

Talimogene laherparepvec, a genetically modified herpes virus used as an oncolytic immunotherapy, was administered to 41 melanoma patients, showing a safety profile similar to previous trials, with only 7.3% experiencing severe treatment-related adverse events.

The treatment led to complete responses in five patients, and the therapy is now approved for use in the US, EU, and Australia, indicating its efficacy in managing unresectable melanoma tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase IIIb safety results from an expanded-access protocol of talimogene laherparepvec for patients with unresected, stage IIIB-IVM1c melanoma. Chesney, J., Awasthi, S., Curti, B., et al.[2018]

Talimogene laherparepvec (T-VEC) showed a significant drop in efficacy from preclinical studies, which reported up to 100% complete regression in tumors, to clinical studies where the highest complete response rate was only 24%.

The study highlighted a high risk of bias in both preclinical and clinical studies, indicating that the promising results seen in the lab may not translate effectively to patient outcomes, underscoring the need for more rigorous and transparent research methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mapping the preclinical to clinical evidence and development trajectory of the oncolytic virus talimogene laherparepvec (T-VEC): a systematic review. Lalu, M., Leung, GJ., Dong, YY., et al.[2020]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02923778

Talimogene Laherparepvec and Radiation Therapy in ... This phase II trial studies the side effects of talimogene laherparepvec and radiation therapy and to see how well they work in treating patients with newly ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34330766/

Intratumoral talimogene laherparepvec injection ... - PubMed We explored a novel combination of TVEC with standard-of-care EBRT administered preoperatively in patients with locally advanced STS of the extremities and ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e23560

Phase 2 study using talimogene laherparepvec, nivolumab ... The results indicate that the combination regimen of Talimogene laherparepvec, Nivolumab, and Trabectedin may be more effective than Trabectedin alone (Median ...

4. asco.org asco.org/abstracts-presentations/ABSTRACT403760

Interim results of a phase 2 study using talimogene ... This study aims to determine the safety and efficacy of adding TVEC to the combination of T and N in advanced leiomyosarcoma (LMS). Methods: Objectives: Primary ...

5. jamanetwork.com jamanetwork.com/journals/jamaoncology/fullarticle/2758838

Objective Response Rate Among Patients With Locally ... Talimogene laherparepvec and pembrolizumab was associated with antitumor activity in advanced sarcoma, across a range of sarcoma histologic subtypes, with a ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37292376/

A phase 1, first-in-child, multicenter study to evaluate the ... We report here the results of a phase 1 study of talimogene laherparepvec (T-VEC) and explore the safety of this oncolytic immunotherapy for the treatment of ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.11570

A phase II study of talimogene laherparepvec (T-VEC) and ... The open-label, single-center phase II study of T-VEC and pembrolizumab in patients with advanced sarcoma met its primary endpoint and demonstrated a best ...