Pembrolizumab + Sunitinib for Thymic Cancer
Recruiting in Palo Alto (17 mi)
+2 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Dwight Owen
Must not be taking: Steroids, Immunosuppressants, CYP3A4/5 inhibitors, CYP3A4/5 inducers
Disqualifiers: Immunodeficiency, Active TB, CNS metastases, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
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.
Will I have to stop taking my current medications?
The trial does not specify if you must stop taking your current medications. However, you cannot use certain drugs that strongly affect liver enzymes (CYP3A4/5 inhibitors or inducers) within 10 days before starting the trial. It's best to discuss your current medications with the trial team.
What data supports the effectiveness of the drug Pembrolizumab for treating thymic cancer?
Research shows that Pembrolizumab, when used alone or with chemotherapy, has been effective in treating thymic cancer, especially in cases with high PD-L1 expression (a protein that helps cancer cells hide from the immune system). Some patients experienced significant tumor reduction and long-term remission, suggesting it could be a promising option for this aggressive cancer.
12345Is the combination of Pembrolizumab and Sunitinib safe for treating thymic cancer?
Pembrolizumab has been used in treating thymic cancer, but it can cause severe immune-related side effects, especially in thymic epithelial tumors, so close monitoring is necessary. There is no specific safety data available for the combination of Pembrolizumab and Sunitinib in thymic cancer, but Pembrolizumab alone has shown both effectiveness and potential for serious side effects.
12356What makes the drug combination of Pembrolizumab and Sunitinib unique for treating thymic cancer?
The combination of Pembrolizumab and Sunitinib is unique for treating thymic cancer because Pembrolizumab is an immune checkpoint inhibitor that targets PD-1, showing promise in tumors with high PD-L1 expression, while Sunitinib is a multi-targeted tyrosine kinase inhibitor that has shown potential in various cancers, including thymic malignancies. This combination leverages both immune modulation and targeted cancer cell inhibition, offering a novel approach for a condition with limited treatment options.
23478Eligibility 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
Be willing to provide peripheral blood samples for correlative studies
Life expectancy greater than 3 months
I can swallow and keep down pills.
+20 more
Exclusion Criteria
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.
+21 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive pembrolizumab intravenously on day 1 and sunitinib malate orally daily on days 1-14. Courses repeat every 21 days for up to 24 months.
24 months
Every 21 days
Follow-up
Participants are monitored for safety and effectiveness after treatment completion. Follow-up occurs every 6 weeks for 1 year, then every 9 or 12 weeks thereafter.
Up to 24 months
Every 6 weeks for 1 year, then every 9 or 12 weeks
Participant Groups
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
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.
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 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 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.
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.
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.
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.