Pembrolizumab + Radiotherapy for Soft Tissue Sarcoma

(SU2C-SARC032 Trial)

Not currently recruiting at 21 trial locations

Overseen By SARC Trials

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Sarcoma Alliance for Research through Collaboration

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Active malignancies, Autoimmune disease, HIV, 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

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether adding pembrolizumab, a type of immunotherapy, to standard radiotherapy before surgery can improve outcomes for people with certain types of soft tissue sarcoma. This cancer affects tissues that connect, support, or surround other structures and organs in the body. Participants will receive either standard radiotherapy alone or pembrolizumab combined with radiotherapy, followed by surgery and additional pembrolizumab. The trial seeks participants with a specific type of soft tissue sarcoma (grade 2 or 3 UPS or certain forms of LPS) in their limbs, without signs of cancer spreading to other parts of the body. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important advancements in cancer therapy.

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 steroid therapy or any form of immunosuppressive therapy, you may need to stop these at least 7 days before starting the trial treatment.

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

Research has shown that pembrolizumab is generally well-tolerated by patients with soft tissue sarcoma. Studies have found that combining pembrolizumab with radiotherapy can help patients with advanced cancer live longer without disease progression.

Regarding safety, patients using pembrolizumab have experienced side effects that are usually manageable. Common side effects resemble those of other cancer treatments, such as tiredness and nausea. However, serious side effects occur less frequently. This suggests that pembrolizumab, when combined with radiotherapy, is relatively safe for most people.

Overall, current research supports the safety of this treatment combination for soft tissue sarcoma, but discussing potential risks with the study team remains important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment for soft tissue sarcoma?

Pembrolizumab is unique because it harnesses the power of the immune system to fight soft tissue sarcoma, which is different from traditional treatments like surgery and radiotherapy alone. Most treatments for this condition focus on removing or shrinking tumors physically, but pembrolizumab is an immunotherapy drug that targets and blocks the PD-1 pathway. This mechanism helps unleash the body's immune response to target and destroy cancer cells more effectively. Researchers are excited about pembrolizumab because it could potentially enhance the effectiveness of radiotherapy, offering a more comprehensive approach to tackling the disease.

What evidence suggests that this trial's treatments could be effective for soft tissue sarcoma?

This trial will compare the effects of adding pembrolizumab to the usual treatment for soft tissue sarcoma. In one arm of the trial, participants will receive neoadjuvant pembrolizumab with concurrent radiotherapy, followed by surgical resection and adjuvant pembrolizumab. Studies have shown that this combination can lead to better outcomes, helping patients live longer without cancer recurrence. Research indicates that pembrolizumab effectively treats advanced stages of this cancer, especially when combined with surgery and radiotherapy. This combination enhances the body’s immune response against the tumor. Additionally, pembrolizumab has shown promise for ongoing treatment, demonstrating success over long periods. ^{1 3 4 6 7}

Who Is on the Research Team?

David Kirsch, MD, PhD

Principal Investigator

Princess Margaret Cancer Center

Are You a Good Fit for This Trial?

This trial is for people aged 12 or older with high-risk soft tissue sarcoma of the extremity that's larger than 5 cm and hasn't spread. Participants must be in good health, have no other active cancers, not had major surgery recently, and agree to use birth control. Those with autoimmune diseases, infections needing treatment, HIV/Hepatitis B/C, or who are pregnant/nursing can't join.

Inclusion Criteria

My cancer is a specific type and grade, and it's larger than 5 cm.

My cancer has not spread and can be surgically removed.

My organs are functioning well, as tested within the last 10 days.

Exclusion Criteria

I have not received a live vaccine in the last 30 days.

I have had pneumonitis treated with steroids or have it now.

I am currently on medication for an infection.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Neoadjuvant pembrolizumab with concurrent radiotherapy followed by surgical resection

Approximately 5 weeks

Multiple visits for radiotherapy sessions

Adjuvant Treatment

Up to fourteen cycles of adjuvant pembrolizumab after surgical resection

1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab

Trial Overview The study compares two treatments: one group receives radiotherapy followed by surgery; the other gets a drug called Pembrolizumab with radiotherapy before surgery and continues Pembrolizumab for a year after. It aims to see if adding Pembrolizumab helps more than just radiotherapy and surgery alone.

How Is the Trial Designed?

Group I: Treatment Experimental Treatment 1 Intervention

Neoadjuvant pembrolizumab with concurrent radiotherapy, followed by surgical resection and adjuvant pembrolizumab.

Group II: Standard of Care Active Control 1 Intervention

Neoadjuvant radiotherapy followed by surgical resection.

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?

Sarcoma Alliance for Research through Collaboration

Lead Sponsor

Trials

26

Recruited

2,000+

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

Stand Up To Cancer

Collaborator

Trials

53

Recruited

40,100+

Published Research Related to This Trial

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating unresectable or metastatic melanoma based on two clinical trials involving 1,374 patients, showing significant improvements in overall survival compared to ipilimumab, with hazard ratios indicating a reduced risk of death.

Patients receiving pembrolizumab also experienced significant improvements in progression-free survival, although some immune-mediated adverse reactions like hypothyroidism and pneumonitis were noted, highlighting the importance of monitoring for side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. Barone, A., Hazarika, M., Theoret, MR., et al.[2022]

In a study of 38 patients with soft tissue sarcoma treated with pembrolizumab, the overall objective response rate was 19.4%, with higher efficacy observed in first-line treatment (42.9%) compared to later lines of therapy.

The median progression-free survival was 2.9 months and overall survival was 12.0 months, indicating limited effectiveness in real-world settings, particularly for certain sarcoma subtypes, and highlighting the potential increased risk of severe adverse events when combined with other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world experience with pembrolizumab in patients with advanced soft tissue sarcoma. Liu, J., Fan, Z., Bai, C., et al.[2022]

Pembrolizumab, an immunotherapy targeting PD-1, showed limited effectiveness in a patient with metastatic renal cell carcinoma, highlighting that only 20-40% of patients benefit from such treatments due to individual tumor biology and immune checkpoint diversity.

The patient's rapid disease progression during treatment may be linked to a lack of tumor-infiltrating lymphocytes (TILs) and the specific radiation dose and schedule used, which could affect the tumor microenvironment and the potential synergy with pembrolizumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune biomarkers of treatment failure for a patient on a phase I clinical trial of pembrolizumab plus radiotherapy. Alexander, GS., Palmer, JD., Tuluc, M., et al.[2022]

In a phase II study of pembrolizumab for advanced sarcoma, a 17.5% response rate was observed, particularly in undifferentiated pleomorphic sarcoma and dedifferentiated liposarcoma, indicating its potential efficacy in these subtypes.

Higher densities of activated T cells and tumor-associated macrophages expressing PD-L1 in pre-treatment biopsies were associated with better responses to pembrolizumab, suggesting that specific immune features may predict treatment outcomes and progression-free survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Correlative Analyses of the SARC028 Trial Reveal an Association Between Sarcoma-Associated Immune Infiltrate and Response to Pembrolizumab. Keung, EZ., Burgess, M., Salazar, R., et al.[2021]

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 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]

Citations

1. medschool.pitt.edu medschool.pitt.edu/news/immunotherapy-drug-pembrolizumab-improves-outcomes-patients-soft-tissue-sarcoma

Immunotherapy Drug Pembrolizumab Improves Outcomes ... Addition of the immunotherapy drug pembrolizumab to standard of care for patients with advanced soft tissue sarcoma of the limb significantly improved disease- ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11236331/

Long Duration Pembrolizumab for Metastatic ... This report is unique owing to the probable longest reporting of successful continuous immunotherapy for metastatic UPS over 6.5 years and 109 cycles.

3. cancerletter.com cancerletter.com/clinical-roundup/20241115_7d/

Keytruda improves outcomes in soft tissue sarcoma Keytruda to standard of care for patients with advanced soft tissue sarcoma of the limb significantly improved disease-free survival.

4. thelancet.com thelancet.com/journals/lancet/article/PIIS0140-6736(24)01812-9/fulltext

Safety and efficacy of pembrolizumab, radiation therapy ... This study showed pembrolizumab activity in patients with metastatic soft tissue sarcomas, with varied response depending on histology. A ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0140673624018129

Safety and efficacy of pembrolizumab, radiation therapy ... Addition of pembrolizumab to preoperative radiotherapy and surgery improves disease-free survival for patients with stage III undifferentiated pleomorphic ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/28988646/

Pembrolizumab in advanced soft-tissue sarcoma and bone ... We assessed pembrolizumab, an anti-PD-1 antibody, for safety and activity in patients with advanced soft-tissue sarcoma or bone sarcoma.

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2020.38.15_suppl.11519

A pilot study evaluating the safety, tolerability, and efficacy ... Conclusions: The combination of pembrolizumab with doxorubicin has manageable toxicity and preliminary promising activity in the treatment of ...