T-VEC + Pembrolizumab for Sarcoma

Recruiting at 4 trial locations

Overseen By Sandra D'Angelo, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

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: Unknown

Duration: 24 weeks

41 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to determine how well the combination of therapy of talimogene laherparepvec (T-VEC) and pembrolizumab works in the treatment of patients with sarcoma.

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, if you are on systemic immunosuppressive therapy or require antiherpetic drugs, you may need to adjust or stop these medications. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment T-VEC + Pembrolizumab for sarcoma?

Research shows that the combination of T-VEC and pembrolizumab is effective in treating sarcomas, as it increases the body's immune response against the tumor. Additionally, this combination has shown promising results in treating advanced melanoma, suggesting its potential effectiveness in other cancers like sarcoma. ^{1 2 3 4 5}

Is the combination of T-VEC and Pembrolizumab safe for humans?

The combination of T-VEC and Pembrolizumab has shown an acceptable safety profile in patients with advanced melanoma, according to a phase III study. This suggests it is generally safe for human use, although specific safety data for sarcoma is not detailed. ^{1 2 3 4 5}

How is the drug T-VEC + Pembrolizumab unique for treating sarcoma?

T-VEC + Pembrolizumab is unique because it combines an oncolytic virus (a virus that targets and destroys cancer cells) with an immune checkpoint inhibitor, which together enhance the body's immune response against sarcoma tumors. This combination is particularly novel for sarcoma, a condition with limited treatment options. ^{1 2 3 6 7}

Research Team

Ciara Kelly, MBBCh BAO

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

Adults with advanced sarcoma, including specific types like epithelioid and cutaneous angiosarcoma, who have tried at least one systemic therapy or refused standard treatment. Participants must be in good health otherwise, not pregnant or breastfeeding, willing to use contraception, and able to give informed consent.

Inclusion Criteria

Willing to comply with treatment protocol

Women who could become pregnant must have a negative pregnancy test before starting the study.

My cancer is one of the specific types: undifferentiated pleomorphic sarcoma, myxofibrosarcoma, epithelioid sarcoma, or cutaneous angiosarcoma.

Exclusion Criteria

Criterion: You are sensitive to talimogene laherparepvec or pembrolizumab, or have a history of lung disease. You have received certain treatments or surgeries within 21 days before the study starts, are currently in another clinical trial, or have had psychiatric or substance abuse issues.

My brain metastases are stable and haven't progressed in the last 4 weeks.

I do not have a weakened immune system due to conditions like HIV, autoimmune diseases, or recent live vaccines.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive talimogene laherparepvec intralesionally and pembrolizumab

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Pembrolizumab
• Talimogene Laherparepvec (T-VEC)

Trial Overview The trial is testing a combination of two drugs: T-VEC (Talimogene Laherparepvec) and Pembrolizumab for treating patients with sarcoma. It aims to see how well these drugs work together against this type of cancer.

Participant Groups

Group I: Talimogene Laherparepvec (T-VEC) Administered with Pembrolizu Experimental Treatment 2 Interventions

Patients will initiate treatment with talimogene laherparepvec given intralesionally and pembrolizumab.

Pembrolizumab is already approved in United States, European Union, United Kingdom for the following indications:

Approved in United States as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in European Union as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in United Kingdom as KEYTRUDA for:

• Untreated metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

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

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Findings from Research

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]

In a phase III study involving 692 patients with advanced melanoma, the combination of talimogene laherparepvec (T-VEC) and pembrolizumab did not significantly improve progression-free survival (PFS) or overall survival (OS) compared to pembrolizumab alone.

The combination therapy showed a higher objective response rate (48.6% vs. 41.3%) and a similar safety profile to the placebo group, with grade ≥ 3 treatment-related adverse events occurring in about 20% of patients in both treatment arms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized, Double-Blind, Placebo-Controlled, Global Phase III Trial of Talimogene Laherparepvec Combined With Pembrolizumab for Advanced Melanoma. Chesney, JA., Ribas, A., Long, GV., et al.[2023]

In a phase 2 trial involving 20 patients with advanced sarcoma, the combination of talimogene laherparepvec (T-VEC) and pembrolizumab achieved a 30% objective response rate at 24 weeks, indicating promising antitumor activity.

The treatment demonstrated a manageable safety profile, with only 20% of patients experiencing grade 3 treatment-related adverse events and no grade 4 events or treatment-related deaths, suggesting it is a safe option for patients with limited treatment alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Objective Response Rate Among Patients With Locally Advanced or Metastatic Sarcoma Treated With Talimogene Laherparepvec in Combination With Pembrolizumab: A Phase 2 Clinical Trial. Kelly, CM., Antonescu, CR., Bowler, T., et al.[2023]

In a phase 2 trial involving 39 patients with advanced sarcomas, the combination treatment of talimogene laherparepvec, trabectedin, and nivolumab showed a 12-month progression-free survival rate of 36.7%, indicating its potential efficacy in this difficult-to-treat cancer.

The treatment was associated with a manageable safety profile, with 50% of patients experiencing grade 3 or higher adverse events, suggesting that while there are risks, the combination therapy is worth further investigation in larger trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Activity of TNT: a phase 2 study using talimogene laherparepvec, nivolumab and trabectedin for previously treated patients with advanced sarcomas (NCT# 03886311). Chawla, SP., Tellez, WA., Chomoyan, H., et al.[2023]

In a phase Ib study involving 34 patients with triple negative breast cancer (TNBC) and colorectal cancer (CRC) with liver metastases, the combination of talimogene laherparepvec (T-VEC) and atezolizumab showed a manageable safety profile, with no dose-limiting toxicities in TNBC patients and a 17% incidence in CRC patients, primarily involving serious adverse events.

Despite the safety of the combination treatment, the efficacy was limited, with only a 10% overall response rate in TNBC and no responses in CRC, indicating that while the treatment is safe, it may not provide significant antitumor benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase Ib study of talimogene laherparepvec in combination with atezolizumab in patients with triple negative breast cancer and colorectal cancer with liver metastases. Hecht, JR., Raman, SS., Chan, A., et al.[2023]

In the phase III OPTiM trial involving 436 patients with advanced melanoma, talimogene laherparepvec (T-VEC) led to a significant reduction in size of injected lesions (64% showed a decrease of ≥50%) and also demonstrated systemic effects by reducing the size of uninjected lesions (34% of non-visceral lesions).

The study found that while some patients experienced progression prior to response (PPR), this did not negatively affect the overall clinical effectiveness of T-VEC, indicating that the treatment can still be effective even if new lesions appear.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patterns of Clinical Response with Talimogene Laherparepvec (T-VEC) in Patients with Melanoma Treated in the OPTiM Phase III Clinical Trial. Andtbacka, RH., Ross, M., Puzanov, I., et al.[2021]

References

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

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

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

Randomized, Double-Blind, Placebo-Controlled, Global Phase III Trial of Talimogene Laherparepvec Combined With Pembrolizumab for Advanced Melanoma. [2023]

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

Objective Response Rate Among Patients With Locally Advanced or Metastatic Sarcoma Treated With Talimogene Laherparepvec in Combination With Pembrolizumab: A Phase 2 Clinical Trial. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Activity of TNT: a phase 2 study using talimogene laherparepvec, nivolumab and trabectedin for previously treated patients with advanced sarcomas (NCT# 03886311). [2023]

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

Phase Ib study of talimogene laherparepvec in combination with atezolizumab in patients with triple negative breast cancer and colorectal cancer with liver metastases. [2023]

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

A Retrospective Chart Review Study of Real-World Use of Talimogene Laherparepvec in Unresectable Stage IIIB-IVM1a Melanoma in Four European Countries. [2021]

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

Patterns of Clinical Response with Talimogene Laherparepvec (T-VEC) in Patients with Melanoma Treated in the OPTiM Phase III Clinical Trial. [2021]