Pembrolizumab + Sunitinib for Thymic Cancer

Recruiting at 2 trial locations

Overseen By The Ohio State University Comprehensive Cancer Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

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 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

Compensation: Varies

Number of Visits: 27

Duration: 24 months

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the combination of pembrolizumab and sunitinib to evaluate their effectiveness in treating thymic cancer that has spread or cannot be surgically removed. Pembrolizumab (KEYTRUDA) is a monoclonal antibody that may inhibit cancer cell growth, while sunitinib (Sutent) blocks enzymes necessary for cell growth. This trial targets individuals whose thymic cancer has not responded to other treatments, such as platinum-based chemotherapy, and who have experienced cancer progression. Participants must have thymic cancer that cannot be cured with available treatments and have already tried at least one chemotherapy regimen. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

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.

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

Research shows that pembrolizumab, when used alone, is generally well-tolerated by patients with advanced thymic carcinoma. Patients might experience side effects, but these are usually manageable. Common side effects include fatigue, rash, or mild digestive issues.

No specific safety information is available for using pembrolizumab with sunitinib in thymic cancer. However, previous studies on pembrolizumab alone have shown it to be safe, suggesting that pembrolizumab might be safe to use. The combination with sunitinib is still under investigation.

For sunitinib, studies on other cancer types have reported side effects like nausea, fatigue, or changes in blood pressure. Most patients manage these side effects, but monitoring is important.

Since this trial is in Phase 2, the combination has shown some safety in earlier trials but is still being studied to confirm these findings. Participants considering joining this trial should discuss potential risks and benefits with their doctors. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining pembrolizumab and sunitinib for thymic cancer because this treatment approach targets the cancer in two distinct ways. Pembrolizumab is an immunotherapy that helps your immune system recognize and attack cancer cells, which is different from traditional chemotherapy that directly kills fast-growing cells. Sunitinib, on the other hand, is a targeted therapy that blocks specific proteins that tumors need to grow. Together, these treatments may offer a powerful one-two punch against thymic cancer, potentially improving outcomes compared to standard therapies.

What evidence suggests that pembrolizumab and sunitinib malate might be an effective treatment for thymic cancer?

Research shows that pembrolizumab, a monoclonal antibody, targets and blocks a protein called PD-1, helping the immune system fight cancer cells. Studies have found pembrolizumab effective in patients with advanced thymic carcinoma, potentially slowing or shrinking the cancer. Sunitinib malate blocks certain enzymes that cancer cells need to grow, which can stop or slow tumor growth. In this trial, participants will receive a combination of pembrolizumab and sunitinib malate. Initial findings suggest that using pembrolizumab and sunitinib together may be more effective than using them separately for treating thymic cancer. Early trials are promising, but more research is needed to confirm these results. ^{1 2 3 6 7}

Who Is on the Research Team?

Dwight Owen, MD

Principal Investigator

Ohio State University Comprehensive Cancer Center

Are You a Good Fit for This Trial?

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.

Be willing to provide peripheral blood samples for correlative studies

Life expectancy greater than 3 months

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab
• Sunitinib Malate

Trial Overview 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.

How Is the Trial Designed?

Group I: Treatment (pembrolizumab, sunitinib malate) Experimental Treatment 3 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

Who Is Running the Clinical Trial?

Dwight Owen

Lead Sponsor

Trials

6

Recruited

210+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

The combination of pembrolizumab and chemotherapy as a first-line treatment for metastatic thymic carcinoma showed promising results in two cases, with one patient achieving a complete response lasting over 3 years and the other a partial response for 20 months.

This study highlights the potential of pembrolizumab combined with chemotherapy in treating advanced thymic carcinoma, suggesting it may be a viable treatment strategy that deserves further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Robust and durable response to first-line treatment of pembrolizumab combined with chemotherapy in two patients with metastatic thymic squamous cell carcinoma: Case report. Chen, C., Sun, P., Long, J.[2022]

Targeted immune checkpoint inhibitors (ICIs) like pembrolizumab and sintilimab show potential in treating advanced thymic epithelial tumors (TETs), particularly thymic carcinoma, but they come with a higher risk of severe immuno-related adverse events.

In a review of four cases, fatal toxicities were observed in patients with metastatic thymomas or carcinomas treated with anti-PD-1 therapy, highlighting the need for close monitoring during treatment due to the association of thymomas with autoimmune disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fatal toxicity induced by anti-PD-1 immune checkpoint inhibitor in thymic epithelial tumor. Jing, X., Zhu, H., Li, Y., et al.[2022]

In a study of 28 patients with thymic epithelial tumors treated with sunitinib, the disease control rate was 63%, indicating that sunitinib can effectively manage these tumors, especially in thymoma patients (86% disease control).

Sunitinib was found to be a tolerable treatment option, with manageable adverse events; however, 8 patients discontinued treatment due to toxicity after an average of 2.7 months, highlighting the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sunitinib in patients with advanced thymic malignancies: Cohort from the French RYTHMIC network. Remon, J., Girard, N., Mazieres, J., et al.[2018]

A 68-year-old woman with advanced thymic carcinoma showed significant tumor reduction after receiving pembrolizumab, a PD-1 inhibitor, as a second-line treatment after chemotherapy failed.

The patient's tumor expressed 100% PD-L1, suggesting that high PD-L1 expression may indicate a better response to pembrolizumab in treating thymic carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful Use of Pembrolizumab to Treat Refractory Thymic Carcinoma with High PD-L1 Expression. Isshiki, T., Isobe, K., Tochigi, N., et al.[2020]

In a phase 2 study involving 41 patients with advanced thymic carcinoma, pembrolizumab showed a response rate of 22.5%, with one patient achieving a complete response and eight achieving partial responses, indicating its potential efficacy as a treatment option.

While pembrolizumab was generally well-tolerated, 15% of patients experienced severe autoimmune toxicity, including cases of myocarditis, highlighting the need for careful monitoring of patients due to the increased risk of autoimmune disorders associated with thymic carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in patients with thymic carcinoma: a single-arm, single-centre, phase 2 study. Giaccone, G., Kim, C., Thompson, J., et al.[2023]

Sunitinib, a multi-targeted tyrosine kinase inhibitor, showed promising results in treating metastatic thymic carcinoma (TC), with three out of four patients experiencing partial remission lasting between 2 to over 18 months.

The overall survival of patients treated with sunitinib ranged from 4 to over 40 months, indicating its potential effectiveness, especially in patients with activated receptor tyrosine kinases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sunitinib in metastatic thymic carcinomas: laboratory findings and initial clinical experience. Ströbel, P., Bargou, R., Wolff, A., et al.[2021]

Pembrolizumab, an anti-PD-1 antibody, shows promising antitumor activity as a treatment option for patients with metastatic thymic carcinomas who have progressed after platinum-based chemotherapy, indicating its potential efficacy in this challenging condition.

In a reported case, a 46-year-old man with metastatic thymic adenocarcinoma achieved a 7.9-month progression-free survival with a combination of pembrolizumab and platinum-based chemotherapy, without severe side effects, suggesting that combining immunotherapy with chemotherapy may enhance treatment outcomes for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Plus Chemotherapy in Metastatic Thymic Carcinoma: A Case Report. Thomas, QD., Basse, C., Luporsi, M., et al.[2022]

In a phase II study of 33 patients with thymic epithelial tumors (TET) who had progressed after platinum-based chemotherapy, pembrolizumab demonstrated encouraging antitumor activity, with 28.6% of thymoma patients and 19.2% of thymic carcinoma patients achieving a partial response.

While pembrolizumab showed efficacy, it was associated with a significant incidence of immune-related adverse events, particularly in patients with thymoma, highlighting the need for further research to optimize treatment and minimize side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for Patients With Refractory or Relapsed Thymic Epithelial Tumor: An Open-Label Phase II Trial. Cho, J., Kim, HS., Ku, BM., et al.[2020]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03463460

NCT03463460 | Pembrolizumab and Sunitinib Malate in ... 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 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10683856/

Pembrolizumab in patients with thymic carcinoma: a single ... We aimed to assess the activity of pembrolizumab, a monoclonal antibody that targets PD-1, in patients with advanced thymic carcinoma.

3. centerwatch.com centerwatch.com/clinical-trials/listings/NCT03463460/pembrolizumab-and-sunitinib-malate-in-treating-participants-with-refractory-metastatic-or-unresectable-thymic-cancer

Pembrolizumab and Sunitinib Malate in Treating ... 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 ...

4. onclive.com onclive.com/view/critical-next-step-in-thymoma-thymic-carcinoma-involves-examining-immunotherapies

Critical Next Step in Thymoma/Thymic Carcinoma Field ... In the US, we [are examining] pembrolizumab plus sunitinib in an ongoing [phase 2] study to see if the combination of the 2 drugs improves ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0169500225004465

Therapeutic management of patients with advanced thymic ... Notably, the combination of gemcitabine and capecitabine demonstrated objective response rates (ORR) of 40 % in patients with thymoma and 38 % in those with ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S016950022300003X

Efficacy and safety of treatments for advanced thymic ... Median OS of 20 months or greater was reported in trials evaluating S-1 or pembrolizumab; this endpoint was not reached in trials evaluating lenvatinib, ...

7. withpower.com withpower.com/trial/phase-3-thymoma-5-2018-80202

Pembrolizumab + Sunitinib for Thymic Cancer There is no specific safety data available for the combination of Pembrolizumab and Sunitinib in thymic cancer, but Pembrolizumab alone has shown both ...