T-VEC + Pembrolizumab for Sarcoma

Not currently 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

Must not be taking: Steroids, Antiherpetics

Disqualifiers: Active infection, CNS metastases, Autoimmune, 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: Unknown

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of combining talimogene laherparepvec (T-VEC) and pembrolizumab (an immunotherapy drug) for individuals with sarcoma, a cancer that begins in bones or soft tissues. The goal is to determine if these treatments can better manage sarcoma that has spread or cannot be surgically removed. Candidates for this trial include those who have tried at least one other systemic treatment, such as chemotherapy or immunotherapy, and have a treatable tumor not located on bone. Participants must have a specific type of sarcoma and at least one tumor that can be injected with the treatment. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to significant advancements in sarcoma treatment.

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.

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

Research has shown that the combination of talimogene laherparepvec (T-VEC) and pembrolizumab has been safe in previous studies. In one study, this treatment was used for patients with advanced sarcoma and was generally well-tolerated. Another study found that this combination had promising effects against certain types of cancer, with safety being acceptable.

These studies suggest that while some side effects might occur, they are not severe for most people. The treatment is still under investigation, so researchers are closely monitoring for any negative effects. Prospective trial participants should discuss any concerns with their healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of T-VEC and pembrolizumab for treating sarcoma because it offers a novel approach compared to existing therapies. Unlike traditional treatments that primarily involve surgery, chemotherapy, and radiation, T-VEC is a genetically modified virus that specifically targets and kills cancer cells, sparing healthy ones. Pembrolizumab, on the other hand, is a type of immunotherapy that boosts the body's natural defenses to fight cancer. This combination aims to enhance the immune response against tumors in a way that current treatments do not, potentially leading to more effective and targeted outcomes.

What evidence suggests that the combination of T-VEC and pembrolizumab could be effective for sarcoma?

Research has shown that combining talimogene laherparepvec (T-VEC) and pembrolizumab holds promise for treating advanced sarcoma. Studies found that this combination achieved important goals, such as shrinking tumors in some patients. These therapies enhance the body's immune system to attack cancer cells more effectively. Previous patients with various types of sarcoma responded positively to this combination. This evidence suggests that T-VEC and pembrolizumab could effectively treat sarcoma. ^{1 2 3 5 6}

Who Is on the Research Team?

Ciara Kelly, MBBCh BAO

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 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 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]

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 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]

Citations

1. 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 ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03069378

NCT03069378 | A Study of Talimogene Laherparepvec (T- ... 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 ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6990941/

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 ...

4. mskcc.org mskcc.org/clinical-updates/combination-immunotherapy-meets-primary-endpoint-phase-ii-clinical-trial-advanced-sarcoma

Combination Immunotherapy Meets Primary Endpoint in ... The combination immunotherapy of talimogene laherparepvec (T-VEC) and pembrolizumab met its primary endpoint of objective response rate at 24 weeks in our ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31971541/

A Phase 2 Clinical Trial - PubMed - NIH In this phase 2 clinical trial, treatment with T-VEC plus pembrolizumab was associated with antitumor activity in advanced sarcoma across a range of sarcoma ...

6. 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 ...