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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests pembrolizumab, a type of immunotherapy, to determine the best dose and understand side effects for people with thymic cancer that cannot be surgically removed. Pembrolizumab aids the immune system in targeting and fighting cancer cells, potentially stopping their growth and spread. The trial suits those with thymoma or thymic carcinoma who have inoperable tumors and have not experienced significant autoimmune diseases like myasthenia gravis or lupus. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this promising therapy.

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.

Is there any evidence suggesting that pembrolizumab is likely to be safe for humans?

Research has shown that pembrolizumab was tested in patients with thymic cancer. In these studies, about 45.5% of patients experienced some side effects. The most common issues were immune-related, such as heart inflammation and liver problems. These early trials primarily aimed to determine the right dose and identify initial side effects. Therefore, more research is necessary to fully understand the safety of pembrolizumab for thymic cancer. Prospective participants should discuss these findings and any concerns with their doctor before joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for thymic cancer, which often involve chemotherapy or radiation, pembrolizumab is a type of immunotherapy that works by boosting the body's own immune system to target and destroy cancer cells. Pembrolizumab is a monoclonal antibody that blocks the PD-1 pathway, which tumors often use to hide from the immune system. This new mechanism of action offers a potentially more precise way to combat cancer, with the hope of fewer side effects than traditional treatments. Researchers are excited because pembrolizumab could provide a more effective treatment option for patients with thymic cancer, especially those who haven't responded well to other therapies.

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

Research has shown that pembrolizumab, which participants in this trial will receive, can help treat thymic cancer. In one study, 22.5% of patients with thymic carcinoma saw their tumors shrink. Another study found an overall response rate of 28.6% for thymoma and 19.2% for thymic carcinoma. Additionally, pembrolizumab reduced tumor size after just three treatment cycles. These findings suggest that pembrolizumab could help the immune system fight thymic cancer by slowing or reducing tumor growth. ^{1 3 6 7 8}

Who Is on the Research Team?

Anne S Tsao

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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]

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]

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]

Citations

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

Pembrolizumab in patients with thymic carcinoma: a single ... The proportion of patients who achieved a response was 22·5% (95% CI 10·8–38·5); one (3%) patient achieved a complete response, eight (20%) patients achieved ...

2. med.amegroups.org med.amegroups.org/article/view/9369/html

Current immunotherapy for thymic epithelial tumors This report showed the ORR of thymoma and thymic carcinoma were 28.6% and 19.2%, respectively. The median PFS was 6.1 months for both thymoma and thymic ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6243955/

Successful Use of Pembrolizumab to Treat Refractory ... After 3 cycles of pembrolizumab treatment, the size of the anterior mediastinal tumor and metastatic lesions had notably decreased. Pembrolizumab may prove to ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S155608642031025X

Durable Response in Patients With Thymic Carcinoma ... The median duration of response was 2.99 years, median progression-free survival was 4.2 months, and median overall survival (OS) was 2.12 years (Fig. 1). The 5 ...

5. acsjournals.onlinelibrary.wiley.com acsjournals.onlinelibrary.wiley.com/doi/full/10.1002/cncr.34678

Understanding the landscape of immunotherapy in thymic ... Of those patients with thymoma, the ORR was 28.6% (two partial responses) and 71.6% (five patients) had stable disease. Of the 26 thymic ...

6. jto.org jto.org/article/S1556-0864(20)31025-X/fulltext

Pembrolizumab in patients with thymic carcinoma Duration of response was approximately 3 years, and median survival was in excess of 2 years with a 5-year survival rate of 18%.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03295227

Study Details | NCT03295227 | Pembrolizumab in Treating ... 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 ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10028091/

Analysis of the efficacy and safety of immunotherapy in ... The incidence of adverse events was 45.5% among the 11 thymoma patients, including immune‐related myocarditis (36.4%), immune‐related liver ...