Trial Summary
What is the purpose of this trial?This phase II trial studies how well pembrolizumab and sunitinib malate work in treating participants with thymic cancer that has spread to other places in the body or cannot be removed by surgery and does not respond to treatment. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread. Sunitinib malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving pembrolizumab and sunitinib malate may work better in treating thymic cancer.
Is the drug Pembrolizumab + Sunitinib promising for treating Thymic Cancer?Yes, Pembrolizumab and Sunitinib show promise for treating Thymic Cancer. Pembrolizumab has been effective in patients with thymic carcinoma, especially those with high PD-L1 expression, and Sunitinib has shown potential in treating advanced thymic malignancies.12345
What safety data exists for Pembrolizumab and Sunitinib in treating thymic cancer?The safety data for Pembrolizumab in treating thymic cancer indicates that while it can be effective, there is a risk of severe immune-related adverse events, especially in thymic epithelial tumors (TETs). Pembrolizumab has shown promise in treating refractory or relapsed thymic carcinoma, particularly in cases with high PD-L1 expression, but close monitoring is necessary due to potential toxicities. There is no specific safety data available for the combination of Pembrolizumab and Sunitinib in thymic cancer from the provided research.45678
What data supports the idea that Pembrolizumab + Sunitinib for Thymic Cancer is an effective drug?The available research shows that Pembrolizumab, when combined with chemotherapy, has shown promising results in treating thymic cancer. In one case, a patient had a complete disappearance of cancer in the chest area for over 3 years, and another patient showed significant improvement for 20 months. Additionally, Pembrolizumab alone has been effective in reducing tumor size in patients whose cancer did not respond to initial treatments. These findings suggest that Pembrolizumab, especially when combined with other treatments, could be an effective option for thymic cancer.34567
Do I need to stop my current medications to join the trial?The trial protocol does not specify if you must stop taking your current medications. However, you cannot use strong CYP3A4/5 inhibitors or inducers within 10 days before starting the trial. It's best to discuss your current medications with the trial team.
Eligibility Criteria
This trial is for adults with advanced thymic cancer that has spread or can't be surgically removed and hasn't responded to platinum-based chemotherapy. Participants must have a life expectancy over 3 months, stable blood pressure, adequate organ function, no severe active infections or autoimmune diseases, not pregnant or breastfeeding, and willing to use contraception.Inclusion Criteria
I can swallow and keep down pills.
I am fully active or restricted in physically strenuous activity but can do light work.
My blood pressure is under control.
My kidney function, measured by creatinine or GFR, is within the normal range.
My thymic carcinoma is advanced and cannot be cured with treatment.
My cancer has worsened after receiving platinum-based chemotherapy.
I am willing to undergo a biopsy for my treatment.
Exclusion Criteria
I have been treated with sunitinib or pembrolizumab before.
I have an active case of tuberculosis.
I have not needed treatment for an autoimmune disease in the last 2 years.
I am currently being treated for an infection.
I have not had a clot in my arteries in the last 6 months.
I have a heart rhythm problem that is moderate to severe.
I have been treated with drugs targeting PD-1, PD-L1, or PD-L2.
I have a serious wound or fracture that is not healing.
I have not received a live vaccine in the last 30 days.
My cancer has spread to my brain or its coverings.
I am using or might need strong medication that affects liver enzymes.
I am not allergic to pembrolizumab or sunitinib.
I have had severe bleeding in the last 4 weeks.
I have another cancer that is getting worse or needs treatment.
I have a history of HIV or active hepatitis B or C.
Treatment Details
The study tests pembrolizumab (a monoclonal antibody) combined with sunitinib malate (an enzyme inhibitor) on participants with refractory metastatic or unresectable thymic cancer. It aims to see if this combination better inhibits tumor growth compared to current treatments.
1Treatment groups
Experimental Treatment
Group I: Treatment (pembrolizumab, sunitinib malate)Experimental Treatment3 Interventions
Participants receive pembrolizumab IV over 30 minutes on day 1 and sunitinib malate PO daily on days 1-14. Courses repeat every 21 days for 24 months in the absence of disease progression or unacceptable toxicity.
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:
Moffitt Cancer CenterTampa, FL
Indiana UniversityIndianapolis, IN
Ohio State University Comprehensive Cancer CenterColumbus, OH
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Who is running the clinical trial?
Dwight OwenLead Sponsor
National Cancer Institute (NCI)Collaborator
References
Sunitinib in metastatic thymic carcinomas: laboratory findings and initial clinical experience. [2021]Thymic carcinoma (TC) is a rare aggressive tumour. Median survival with current treatments is only 2 years. Sunitinib is a multi-targeted tyrosine kinase inhibitor that has shown benefit in various other cancers.
Sunitinib in patients with advanced thymic malignancies: Cohort from the French RYTHMIC network. [2018]Sunitinib is a potent oral tyrosine kinase inhibitor of VEGFRs, KIT, and PDGFRs. In a single arm phase II trial, sunitinib has demonstrated its potential activity in refractory thymic carcinoma (TC) and thymoma (T). Taking advantage of the French RYTHMIC network prospective database, we investigated the off-label efficacy of sunitinib in previously-treated thymic epithelial tumors (TETs) patients not included in a clinical trial.
Pembrolizumab in patients with thymic carcinoma: a single-arm, single-centre, phase 2 study. [2023]Treatment options are limited for patients with thymic carcinoma. These aggressive tumours are not typically associated with paraneoplastic autoimmune disorders, and strong PD-L1 expression has been reported in thymic epithelial tumours. We aimed to assess the activity of pembrolizumab, a monoclonal antibody that targets PD-1, in patients with advanced thymic carcinoma.
Pembrolizumab for Patients With Refractory or Relapsed Thymic Epithelial Tumor: An Open-Label Phase II Trial. [2020]Limited treatment options exist for patients with thymic epithelial tumor (TET) whose disease progresses after platinum-based chemotherapy. We conducted a phase II study of pembrolizumab in patients with TET to evaluate its efficacy and safety.
Successful Use of Pembrolizumab to Treat Refractory Thymic Carcinoma with High PD-L1 Expression. [2020]Thymic carcinoma is a relatively rare and aggressive thymic epithelial tumor. Herein, we report successful treatment of thymic carcinoma with pembrolizumab. A 68-year-old woman was admitted to our hospital for evaluation of chest pain. Chest computed tomography showed a mass in the anterior mediastinum and lymphadenopathy in the left cervical lymph node. Analysis of biopsy specimens detected squamous cell carcinoma in the left cervical lymph node, and immunohistochemical analysis showed 100% expression of programmed death-ligand 1 (PD-L1). Masaoka-Koga stage IVb thymic carcinoma was ultimately diagnosed. Since 3 cycles of first-line chemotherapy did not result in improvement, pembrolizumab was administered as second-line treatment every 3 weeks at a dosage of 200 mg. After 3 cycles of pembrolizumab treatment, the size of the anterior mediastinal tumor and metastatic lesions had notably decreased. Pembrolizumab may prove to be an effective therapy for thymic carcinoma with high PD-L1 expression.
Pembrolizumab Plus Chemotherapy in Metastatic Thymic Carcinoma: A Case Report. [2022]Metastatic thymic carcinomas have a poor prognosis. Pembrolizumab, an anti-PD-1 antibody, has recently been evaluated for patients with metastatic thymic carcinomas progressing after at least one line of platinum-based chemotherapy. The antitumor activity of immunotherapy appears to be promising for these patients and pembrolizumab in monotherapy is actually a treatment option in second metastatic line. To the best of our knowledge, we report the first case of a patient treated for metastatic thymic adenocarcinoma with a combination of chemotherapy-immunotherapy. The patient is a 46-year-old man with metastatic thymic adenocarcinoma treated in third metastatic line with a combination of pembrolizumab plus platinum-based chemotherapy with a very good metabolic tumor response. He had a progression-free survival of 7.9 months and did not experience any severe side effects related to pembrolizumab. The association of immunotherapy and chemotherapy, as in non-small cell and small cell lung cancers, could be of interest for future therapeutic trials evaluating the survival of patients with metastatic thymic carcinoma.
Robust and durable response to first-line treatment of pembrolizumab combined with chemotherapy in two patients with metastatic thymic squamous cell carcinoma: Case report. [2022]Thymic carcinoma is a rare and aggressive disease with poor outcome. There is no established treatment regimen for advanced thymic carcinoma. While the efficacy of pembrolizumab was proved to be promising, as a single agent, in patients with refractory/recurrent thymic carcinoma that progressed after chemotherapy, the efficacy and safety of combination of pembrolizumab and chemotherapy as front-line treatment in metastatic thymic carcinoma have not been explored yet. Herein, we report the first two cases of metastatic thymic squamous cell carcinoma receiving the combined approaches of pembrolizumab and chemotherapy as first-line treatment. Of the two patients, one had a complete radiological response of mediastinal masses with sustained remission over 3 years, and the other one with widespread disease had a good partial response over 20 months and achieved no evidence of disease radiologically after undergoing percutaneous radiofrequency ablation for residual liver metastases. Next-generation sequencing (NGS) showed low tumor mutation burden and MSS in both patients. Immunohistochemistry analysis of the tumor showed high PD-L1 expression in patient 1 and low PD-L1 expression in patient 2. Pembrolizumab combined with chemotherapy may be an attractive strategy for the first-line treatment of metastatic thymic carcinoma and thus warrants further evaluation.
Fatal toxicity induced by anti-PD-1 immune checkpoint inhibitor in thymic epithelial tumor. [2022]A standard treatment for advanced thymic epithelial tumors (TETs) after initial treatment remains unavailable to date. Targeted immune checkpoint inhibitors (ICIs) of the programmed cell death-1 (PD-1) pathway may produce objective responses in TETs, notably thymic carcinoma. Findings of clinical trials suggested ICIs are a practical choice. However, the risk of severe immuno-related adverse events is higher in TETs. Concerning histologic subtypes, thymomas are more frequently associated with autoimmune disorders than carcinomas, so close monitoring is needed for thymomas. In this article, we describe four cases of fatal toxicity caused by anti-PD-1 therapy in TETs. Four patients with metastatic thymomas or carcinoma difficult to treat with first-line standard chemotherapy were treated with the anti-PD-1 drug pembrolizumab or sintilimab. The association of PD-1 inhibitors with a high proportion of severe immuno-related adverse events in TETs necessitates attentive monitoring during treatment.