Talimogene Laherparepvec for Soft Tissue Sarcoma

Overseen By John Rieth, MD

Age: 18+

Sex: Any

Trial Phase: Phase < 1

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)

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

Compensation: Varies

Number of Visits: Unknown

Duration: Concurrent with radiation until surgery

30 Participants Needed

Trial Summary

What is the purpose of this trial?

The proposed study is designed to treat locally advanced soft tissue sarcoma (STS) subtypes with neoadjuvant talimogene laherparepvec (TVEC) and preoperative external beam radiation therapy (EBRT).

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.

What data supports the effectiveness of the treatment Talimogene Laherparepvec for Soft Tissue Sarcoma?

Talimogene laherparepvec (T-VEC) has shown effectiveness as an oncolytic virus therapy for melanoma, where it is used to treat tumors by injecting the virus directly into them, helping the immune system attack cancer cells. While this data is specific to melanoma, it suggests potential for T-VEC in treating other types of tumors, like soft tissue sarcoma, by a similar mechanism. ^{1 2 3 4 5}

How is the drug Talimogene Laherparepvec unique for treating soft tissue sarcoma?

Talimogene Laherparepvec is unique because it is an oncolytic virus therapy, meaning it uses a modified virus to target and destroy cancer cells, which is different from traditional chemotherapy or radiation treatments. It is delivered directly into the tumor (intralesionally), which can help stimulate the body's immune response against the cancer. ^{1 2 3 4 5}

Research Team

John Rieth, MD

Principal Investigator

University of Iowa

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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 (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]

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]

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]

References

1. England 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. [2018]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Biodistribution, shedding, and transmissibility of the oncolytic virus talimogene laherparepvec in patients with melanoma. [2020]

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

Talimogene Laherparepvec: An Oncolytic Virus Therapy for Melanoma. [2018]

4. England 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. [2020]

5. England pubmed.ncbi.nlm.nih.gov

Observational study of talimogene laherparepvec use for melanoma in clinical practice in the United States (COSMUS-1). [2022]