Pembrolizumab for Thymic Cancer

Recruiting at 1 trial location

Overseen By Anne S. Tsao

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Active TB, Active hepatitis, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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: 27

Duration: Up to 2 years

37 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase I trial studies the sides effects and best dose of pembrolizumab in treating participants with thymoma or thymic cancer that cannot be removed by surgery. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

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 cannot be on systemic steroid therapy or any other form of immunosuppressive therapy within 7 days before starting the trial treatment.

What data supports the effectiveness of the drug pembrolizumab for thymic cancer?

Research shows that pembrolizumab, when used alone or with chemotherapy, can lead to significant tumor reduction and long-lasting responses in patients with thymic carcinoma, especially those with high PD-L1 expression. Some patients experienced complete or partial responses lasting over 20 months, and a study reported a 5-year survival rate of 18%. ^{1 2 3 4 5}

Is pembrolizumab safe for treating thymic cancer?

Pembrolizumab has been used in patients with thymic cancer, and while it can lead to durable responses, there is a higher than expected risk of severe autoimmune disorders (conditions where the immune system attacks the body) in about 15% of patients. Careful monitoring for side effects is important when using this treatment. ^{1 2 3 4 5}

How is the drug pembrolizumab unique in treating thymic cancer?

Pembrolizumab is unique for thymic cancer because it targets PD-1, a protein that helps cancer cells evade the immune system, and it has shown promise when combined with chemotherapy, especially in cases with high PD-L1 expression. This combination approach is novel as there are no established treatments for advanced thymic carcinoma. ^{1 2 3 5 6}

Research Team

Anne S Tsao

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for people with thymoma or thymic cancer that can't be surgically removed. Participants must not have significant autoimmune diseases, active hepatitis, HIV, or a history of certain treatments within specific time frames. They should have normal organ function tests and agree to use contraception if applicable.

Inclusion Criteria

I have received previous treatments for my condition.

I do not have active hepatitis or HIV.

My liver function tests are within the required range.

Exclusion Criteria

I haven't had cancer treatment with a monoclonal antibody in the last 4 weeks or have recovered from its side effects.

I have stable brain metastases, not on steroids for 7 days, and no carcinomatous meningitis.

I have had pneumonitis treated with steroids or have it now.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab intravenously over 30 minutes on day 1, with courses repeating every 21 days for up to 2 years

Up to 2 years

Every 21 days

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

1 year with visits every 6 weeks, then every 3 months for up to 3 years

Every 6 weeks for 1 year, then every 3 months

Treatment Details

Interventions

• Pembrolizumab

Trial Overview The trial is testing the safety and optimal dosage of pembrolizumab, an immunotherapy drug designed to help the immune system fight cancer by blocking tumor growth. It's given to patients who meet strict health criteria and are willing to provide tissue samples for research.

Participant Groups

Group I: Treatment (pembrolizumab) Experimental Treatment 1 Intervention

Participants receive pembrolizumab IV over 30 minutes on day 1. Courses repeat every 21 days for up to 2 years 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?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

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

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

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]

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 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]

Pembrolizumab shows promising efficacy in patients with advanced thymic carcinoma, with a duration of response lasting approximately 3 years and a median survival exceeding 2 years, along with a 5-year survival rate of 18%.

Despite a notable incidence of severe autoimmune disorders (15%), the risk did not significantly increase with longer follow-up, indicating that while monitoring for toxicities is essential, the treatment can still be considered durable and effective.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durable Response in Patients With Thymic Carcinoma Treated With Pembrolizumab After Prolonged Follow-Up. Giaccone, G., Kim, C.[2022]

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]

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]

References

1. Switzerland 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. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Successful Use of Pembrolizumab to Treat Refractory Thymic Carcinoma with High PD-L1 Expression. [2020]

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

Pembrolizumab for Patients With Refractory or Relapsed Thymic Epithelial Tumor: An Open-Label Phase II Trial. [2020]

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

Durable Response in Patients With Thymic Carcinoma Treated With Pembrolizumab After Prolonged Follow-Up. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab in patients with thymic carcinoma: a single-arm, single-centre, phase 2 study. [2023]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Pembrolizumab Plus Chemotherapy in Metastatic Thymic Carcinoma: A Case Report. [2022]