Pembrolizumab for Thymic Cancer

Recruiting in Palo Alto (17 mi)

+1 other location

Overseen by Anne S Tsao

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Active TB, Active hepatitis, HIV, others

No Placebo Group

Breakthrough Therapy

Approved in 3 Jurisdictions

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}

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.

Trial 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 (Checkpoint Inhibitor)

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

M D Anderson Cancer Center Houston, TX

University of Texas MD Anderson Cancer Center Houston, TX

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center Lead Sponsor

Merck Sharp & Dohme LLC Industry Sponsor

National Cancer Institute (NCI) Collaborator

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] 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.

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

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.

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] 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.

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

Durable Response in Patients With Thymic Carcinoma Treated With Pembrolizumab After Prolonged Follow-Up. [2022] Here, we present an update of a phase 2 study of pembrolizumab in patients with advanced thymic carcinoma who failed previous therapies. Duration of response was approximately 3 years, and median survival was in excess of 2 years with a 5-year survival rate of 18%. The higher than expected incidence of severe autoimmune disorders (15%) did not substantially increase with a longer follow-up. Pembrolizumab induces durable responses in patients with thymic carcinoma. Careful selection of patients and monitoring of toxicities are warranted.

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

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.

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

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.