Pembrolizumab + Radiotherapy for Sarcoma
Recruiting in Palo Alto (17 mi)
Overseen ByJeremy Harris, MD, MPhil
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase < 1
Recruiting
Sponsor: University of California, Irvine
No Placebo Group
Breakthrough Therapy
Approved in 3 jurisdictions
Trial Summary
What is the purpose of this trial?This trial is testing a combination of a drug that helps the immune system fight cancer and a precise form of radiation therapy. It targets patients with soft-tissue sarcoma whose cancer has spread or cannot be cured with surgery. The drug boosts the immune system, and the radiation targets tumors directly.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications. However, you must not be on active immunosuppression within 7 days before starting the treatment, and you cannot be receiving other investigational agents.
What data supports the effectiveness of the drug pembrolizumab for treating sarcoma?
Research shows that pembrolizumab, a drug that helps the immune system fight cancer, has been tested in patients with advanced sarcomas, showing some activity and safety. It has also been effective in treating other types of cancers, like lung cancer and melanoma, which suggests it might help with sarcoma too.
12345Is the combination of Pembrolizumab and Radiotherapy safe for humans?
Pembrolizumab, also known as Keytruda, has been used in various cancer treatments and is generally considered safe, but it can cause side effects like fatigue, cough, nausea, and more serious immune-related reactions such as pneumonitis (lung inflammation) and thyroid disorders. While specific safety data for the combination with radiotherapy in sarcoma is limited, Pembrolizumab alone has been studied in other cancers with known safety profiles.
45678What makes the treatment with pembrolizumab and radiotherapy unique for sarcoma?
This treatment is unique because it combines pembrolizumab, a drug that helps the immune system attack cancer cells, with radiotherapy, which can enhance the immune response against tumors. This combination aims to improve the effectiveness of treatment by using the body's own defenses alongside traditional cancer therapy.
5691011Eligibility Criteria
Adults with advanced or recurrent soft-tissue sarcoma, not eligible for curative surgery. Must have measurable lesions, life expectancy over 3 months, and proper organ/marrow function. HIV-positive patients can join if viral load is undetectable. Excludes pregnant/nursing women, those on active immunosuppression, with recent chemotherapy/radiotherapy or other investigational agents.Participant Groups
The trial tests the combination of pembrolizumab (an immunotherapy drug) and stereotactic ablative radiotherapy (SBRT) in treating metastatic sarcoma. It aims to see if this combo is feasible for patients who've had previous systemic therapy or are ineligible for it.
2Treatment groups
Experimental Treatment
Group I: B: Radiation Therapy with or without standard of care checkpoint inhibitor immunotherapyExperimental Treatment1 Intervention
Patients who are currently receiving a checkpoint inhibitor immunotherapy regimen will be allowed to continue their regimen at their treating oncologist's discretion. Radiation therapy will be delivered in 1 to 10 fractions starting on Day 1.
Group II: A: Pembrolizumab + Radiation TherapyExperimental Treatment2 Interventions
Patients receive pembrolizumab 400 mg intravenous every 42 days; Radiation therapy in 1 to 10 fractions.
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
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Chao Family Comprehensive Cancer Center, University of California, IrvineOrange, CA
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Who is running the clinical trial?
University of California, IrvineLead Sponsor
References
New Approved Use for Keytruda. [2022]Pembrolizumab (Keytruda) is now approved as a single agent to treat advanced endometrial carcinoma that is microsatellite instability-high or mismatch repair deficient in those whose disease has progressed following prior systemic therapy in any setting and who are not candidates for curative surgery or radiation.
Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]A phase II trial investigating the therapeutic effect of neoadjuvant programmed cell death 1 (PD-1) inhibitor pembrolizumab (MK-3475, KEYTRUDA®) administered prior to surgery for the treatment of non-small cell lung cancer (NSCLC) has been conducted (NCT03197467). We report the first clinical results of a planned interim safety analysis after 15 patients were enrolled.
Pembrolizumab in advanced osteosarcoma: results of a single-arm, open-label, phase 2 trial. [2022]To evaluate the activity and safety of the PD-1 antibody pembrolizumab in adult patients with advanced osteosarcoma.
Pembrolizumab in advanced soft-tissue sarcoma and bone sarcoma (SARC028): a multicentre, two-cohort, single-arm, open-label, phase 2 trial. [2022]Patients with advanced sarcomas have a poor prognosis and few treatment options that improve overall survival. Chemotherapy and targeted therapies offer short-lived disease control. We assessed pembrolizumab, an anti-PD-1 antibody, for safety and activity in patients with advanced soft-tissue sarcoma or bone sarcoma.
Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]New insights into the interaction between the immune system and the tumor microenvironment have led to the development of checkpoint inhibitors that target the PD-1/PD-L1 pathway. Pembrolizumab (MK-3475, lambrolizumab, Keytruda(®)) is a PD-1 inhibitor that has shown clinical activity in a variety of solid tumors and is currently approved for the second-line treatment of PD-L1-positive non-small-cell lung cancer and for unresectable/metastatic melanoma. This article will discuss the results of early-phase trials of pembrolizumab in thoracic malignancies as well as ongoing studies aimed to confirm clinical benefit.
FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]On September 4, 2014, the FDA approved pembrolizumab (KEYTRUDA; Merck Sharp & Dohme Corp.) with a recommended dose of 2 mg/kg every 3 weeks by intravenous infusion for the treatment of patients with unresectable or metastatic melanoma who have progressed following treatment with ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. Approval was based on demonstration of objective tumor responses with prolonged response durations in 89 patients enrolled in a randomized, multicenter, open-label, dose-finding, and activity-estimating phase 1 trial. The overall response rate (ORR) by blinded independent central review per RECIST v1.1 was 24% (95% confidence interval, 15-34); with 6 months of follow-up, 86% of responses were ongoing. The most common (≥20%) adverse reactions were fatigue, cough, nausea, pruritus, rash, decreased appetite, constipation, arthralgia, and diarrhea. Immune-mediated adverse reactions included pneumonitis, colitis, hepatitis, hypophysitis, and thyroid disorders. The benefits of the observed ORR with prolonged duration of responses outweighed the risks of immune-mediated adverse reactions in this life-threatening disease and represented an improvement over available therapy. Important regulatory issues in this application were role of durability of response in the evaluation of ORR for accelerated approval, reliance on data from a first-in-human trial, and strategies for dose selection. Clin Cancer Res; 23(19); 5666-70. ©2017 AACR.
Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. [2023]Pembrolizumab (Keytruda) is a monoclonal antibody against the programmed cell death-1 (PD-1) receptor on lymphocytes, which is one of the immune checkpoint inhibitors (ICIs) approved for multiple solid and hematologic malignancies. Although ICIs have proven to be more effective and less toxic compared to chemotherapy, there are reports of adverse side effects with ICIs. For example, pneumonitis is a potentially lethal side effect occurring in 1%-5% of patients who received ICIs in clinical trials, and there are case reports with clinical and radiological features of checkpoint inhibitor-pneumonitis (CIP).
Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. [2022]Pembrolizumab (Keytruda; Merck Sharp & Dohme) is a humanized IgG4 monoclonal antibody used in cancer immunotherapy. It targets the programmed cell death-1 (PD-1) receptor, which is important in maintaining self-tolerance. However, immune checkpoint blockade is associated with a risk for immune-related adverse events (irAEs) potentially affecting the endocrine organs. Type 1 diabetes mellitus is a rare irAE of PD-1 inhibitors, occurring in 0.2% of cases.
Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. [2017]Pembrolizumab (MK-3475) is a monoclonal antibody that binds to the PD-1 receptor on T cells and prevents binding to its ligands PD-L1 and PD-L2. Blocking this receptor frees T cells from the inhibitory effects of PD-L1 and allows them to mediate antitumor effects against cancer cells. In a large Phase I study of 411 patients with melanoma, high durable response rates over a range of doses and schedules have been shown with very little toxicity. A Phase III study of pembrolizumab comparing two schedules of administration with the current standard treatment with the anti-CTLA-4 monoclonal antibody is in progress. Combinations with other checkpoint inhibitors as well as other anticancer agents are also being evaluated. Approval of pembrolizumab for the treatment of melanoma is expected.
Immune biomarkers of treatment failure for a patient on a phase I clinical trial of pembrolizumab plus radiotherapy. [2022]Pembrolizumab is a monoclonal antibody that is designed against programmed cell death protein 1 (PD-1). Pembrolizumab and other immunocheckpoint-blocking monoclonal antibodies work by modulating a patient's own immune system to increase anti-tumor activity. While immunocheckpoint blockade has shown promising results, only 20-40 % of patients experience objective clinical benefit. Differences in individual tumor biology and the presence multiple immune checkpoints present a challenge for treatment. Because radiotherapy has immunomodulatory effects on the tumor microenvironment, it has the potential to synergize with immunotherapy and augment tumor response. NCT02318771 is a phase 1 clinical trial designed to investigate the immunomodulatory effects of radiation therapy in combination with pembrolizumab.
Acute myelomonocytic leukemia during pembrolizumab treatment for non-small cell lung cancer: A case report. [2020]Pembrolizumab is a highly selective IgG4 kappa isotype monoclonal antibody against the programmed cell death-1 (PD-1) molecule. In the treatment of non-small cell lung cancer (NSCLC), pembrolizumab has demonstrated significant efficacy, significant survival outcomes, long-lasting responses, and a good safety profile compared with cytotoxic chemotherapy.