Pembrolizumab + Radiotherapy for Soft Tissue Sarcoma

(SU2C-SARC032 Trial)

Recruiting at 19 trial locations

Overseen By SARC Trials

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Sarcoma Alliance for Research through Collaboration

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

126 Participants Needed

Trial Summary

What is the purpose of this trial?

This is an open-label, multi-institutional phase II randomized study comparing neoadjuvant radiotherapy followed by surgical resection to neoadjuvant pembrolizumab with concurrent radiotherapy, followed by surgical resection and adjuvant pembrolizumab. The total duration of pembrolizumab will be one year in the experimental arm.

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.

What data supports the effectiveness of the drug pembrolizumab for soft tissue sarcoma?

Research shows that pembrolizumab, a drug that helps the immune system fight cancer, had a 17.5% response rate in patients with advanced sarcoma, particularly in certain types like undifferentiated pleomorphic sarcoma and dedifferentiated liposarcoma. This suggests it may help some patients with these specific sarcoma types. ^{1 2 3 4 5}

Is pembrolizumab safe for humans?

Pembrolizumab, also known as KEYTRUDA, has been used in various clinical trials and is generally considered safe for humans, though it can cause side effects like fatigue, cough, nausea, and immune-related issues such as thyroid problems and lung inflammation. It has been approved for use in conditions like melanoma, indicating that its benefits outweigh the risks in certain serious diseases. ^{1 3 4 5 6}

How is the drug pembrolizumab combined with radiotherapy unique for treating soft tissue sarcoma?

Pembrolizumab is a drug that helps the immune system fight cancer by blocking a protein called PD-1, which can stop the immune system from attacking cancer cells. When combined with radiotherapy, which can also affect the immune system, this treatment may enhance the body's ability to fight soft tissue sarcoma, offering a novel approach compared to traditional chemotherapy. ^{1 3 5 7 8}

Research Team

David Kirsch, MD, PhD

Principal Investigator

Princess Margaret Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

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 (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]

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]

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]

References

1. England 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. [2022]

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

Correlative Analyses of the SARC028 Trial Reveal an Association Between Sarcoma-Associated Immune Infiltrate and Response to Pembrolizumab. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]

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

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]

5. China pubmed.ncbi.nlm.nih.gov

Real-world experience with pembrolizumab in patients with advanced soft tissue sarcoma. [2022]

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

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Immune biomarkers of treatment failure for a patient on a phase I clinical trial of pembrolizumab plus radiotherapy. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. [2017]