Pembrolizumab for Thyroid Cancer

Overseen by Saad Khan, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Stanford University

Must not be taking: Anti-PD-1, Anti-PD-L1

Disqualifiers: Immunodeficiency, Active infection, Autoimmune, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

This is a single-arm, open-label trial designed to evaluate the activity of pembrolizumab therapy in anaplastic thyroid cancer in patients with no curative alternative therapy. Pembrolizumab (Keytruda-Merck) 200 mg, given IV every 3 weeks, until evidence of progression, intolerance of treatment, withdrawal of consent or death

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are taking dabrafenib, trametinib, or lenvatinib, you will need a 1-week break from these before starting the trial.

What data supports the effectiveness of the drug Pembrolizumab for thyroid cancer?

Research shows that Pembrolizumab has been effective in treating advanced thyroid cancer, particularly in patients whose cancer expresses a specific protein called PD-L1. Additionally, Pembrolizumab has shown significant benefits in other cancers, like lung cancer, which suggests it might also help in thyroid cancer. ^{1 2 3 4 5}

Is pembrolizumab safe for humans?

Pembrolizumab has been associated with some immune-related side effects, including thyroid problems like hypothyroidism (underactive thyroid) and hyperthyroidism (overactive thyroid), as well as rare cases of Graves' disease and type 1 diabetes. These side effects are important to consider when evaluating its safety. ^{1 2 6 7 8}

How is the drug pembrolizumab unique for treating thyroid cancer?

Pembrolizumab is unique for treating thyroid cancer because it is an immune checkpoint inhibitor that targets the PD-1 receptor, helping the immune system attack cancer cells, and is used for advanced cases where standard treatments are ineffective. It is particularly used for thyroid cancers that express PD-L1, a protein that helps tumors evade the immune system. ^{1 2 3 4 8}

Research Team

Saad Khan, MD

Principal Investigator

Stanford University

Eligibility Criteria

Adults with advanced anaplastic or undifferentiated thyroid cancer, who have no curative treatment options left. Participants must have certain blood cell counts within a healthy range, measurable disease progression, and be in relatively good physical condition (ECOG 0-1). They should not be pregnant and agree to use contraception. Exclusions include recent other cancer treatments, live vaccines, active infections like HIV or hepatitis B/C, autoimmune diseases needing treatment in the last 2 years, severe allergies to pembrolizumab components.

Inclusion Criteria

I am fully active or restricted in physically strenuous activity but can do light work.

My thyroid cancer has spread, but it's either been fully removed by surgery or doesn't need neck surgery/radiation.

I've had radiation or surgery for my tumor and now have ATC/UTC.

Exclusion Criteria

I have previously been treated with specific immunotherapy drugs.

I have a history of HIV, Hepatitis B, or Hepatitis C.

I have not received a live vaccine in the last 30 days.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab 200 mg IV every 3 weeks for up to 35 cycles (approximately 2 years) or until disease progression, unacceptable toxicity, or withdrawal

Approximately 2 years

IV infusion every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Treatment Details

Interventions

• Pembrolizumab (PD-1 Inhibitor)

Trial Overview The trial is testing Pembrolizumab (Keytruda), given intravenously every three weeks at a dose of 200 mg. It continues until the patient's disease progresses further, they can't tolerate it anymore, withdraw consent or pass away. The goal is to see how effective this drug is for treating this type of thyroid cancer.

Participant Groups

Group I: Pembrolizumab 200 mg Experimental Treatment 1 Intervention

Participants will receive pembrolizumab (Keytruda) 200 mg administered by IV infusion every 3 weeks. Participants will remain on study and receive pembrolizumab for the nominal duration of treatment (35 cycles, approximately 2 years) or until there is evidence of disease progression by RECIST, unacceptable toxicity, withdrawal of consent, or discontinuation of the trial for any other reason.

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

Dr. Richard A. Miller

Stanford University

Chief Executive Officer since 2023

Stanford University, MD

Dr. Robert Schott

Stanford University

Chief Medical Officer since 2021

University of Michigan, MD

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

Findings from Research

In a phase Ib trial involving 22 patients with advanced differentiated thyroid cancer, pembrolizumab showed a manageable safety profile, with 82% experiencing treatment-related adverse events, primarily diarrhea and fatigue, but no treatment-related deaths.

The treatment demonstrated limited efficacy, with an objective response rate of 9% and a median progression-free survival of 7 months, indicating that while some patients may benefit, further research is needed to confirm these results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and antitumor activity of the anti-PD-1 antibody pembrolizumab in patients with advanced, PD-L1-positive papillary or follicular thyroid cancer. Mehnert, JM., Varga, A., Brose, MS., et al.[2020]

Pembrolizumab, an immune checkpoint inhibitor, has shown significant long-term survival benefits for lung cancer patients, highlighting its efficacy in cancer treatment.

The case study emphasizes the need for vigilance in monitoring thyroid health in lung cancer patients receiving pembrolizumab, as new thyroid lesions may indicate primary thyroid cancer rather than just metastatic disease or treatment-related thyroiditis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of Thyroid Carcinoma During Treatment With Pembrolizumab in a Lung Cancer Patient. Gorospe, L., García-Gómez-Muriel, I., Pian-Arias, HG., et al.[2020]

In a study of 103 patients with advanced thyroid cancer, pembrolizumab showed a modest objective response rate of 6.8%, with a median duration of response lasting 18.4 months, indicating some effectiveness in this challenging cancer type.

The treatment was associated with manageable toxicity, as 69.9% of patients experienced treatment-related adverse events, but only 14.6% had severe (grade 3-5) reactions, suggesting that pembrolizumab can be safely administered to this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of pembrolizumab monotherapy in patients with advanced thyroid cancer in the phase 2 KEYNOTE-158 study. Oh, DY., Algazi, A., Capdevila, J., et al.[2023]

In a systematic review of four randomized clinical trials involving 1603 patients with advanced or metastatic non-small cell lung cancer (NSCLC), Pembrolizumab was found to cause thyroid dysfunction in 19.8% of patients.

The treatment with Pembrolizumab significantly increased the risk of thyroid dysfunction by 3.9 times compared to controls, highlighting a notable side effect associated with this cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence and Risk of Thyroid Dysfunction in Advanced or Metastatic Non-small Cell Lung Cancer Patients Treated with Pembrolizumab: A Meta-analysis. Abid, H., Khavandi, M., Siddiqui, N., et al.[2020]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating unresectable or metastatic melanoma based on two clinical trials involving 1,374 patients, showing significant improvements in overall survival compared to ipilimumab, with hazard ratios indicating a reduced risk of death.

Patients receiving pembrolizumab also experienced significant improvements in progression-free survival, although some immune-mediated adverse reactions like hypothyroidism and pneumonitis were noted, highlighting the importance of monitoring for side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. Barone, A., Hazarika, M., Theoret, MR., et al.[2022]

Immune checkpoint inhibitors like pembrolizumab can lead to various immune-related adverse events, with thyroid dysfunction being a common issue.

This report highlights a rare case of Graves' disease causing thyrotoxicosis in a 50-year-old patient undergoing pembrolizumab therapy, emphasizing the need for awareness of this potential side effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Rare Case of Pembrolizumab-Associated Graves' Disease. Alqaisi, S., Rahman, A.[2023]

Pembrolizumab, a PD-1 inhibitor used in cancer treatment, can lead to rare but serious immune-related adverse events, including type 1 diabetes mellitus, occurring in about 0.2% of cases.

A review of 42 cases revealed that patients may develop diabetic ketoacidosis during treatment, highlighting the need for blood glucose monitoring and awareness of this potential side effect among clinicians.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. Clotman, K., Janssens, K., Specenier, P., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Safety and antitumor activity of the anti-PD-1 antibody pembrolizumab in patients with advanced, PD-L1-positive papillary or follicular thyroid cancer. [2020]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Development of Thyroid Carcinoma During Treatment With Pembrolizumab in a Lung Cancer Patient. [2020]

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

Efficacy and safety of pembrolizumab monotherapy in patients with advanced thyroid cancer in the phase 2 KEYNOTE-158 study. [2023]

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

Pembrolizumab: An Immunotherapeutic Agent Causing Endocrinopathies. [2020]

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

Incidence and Risk of Thyroid Dysfunction in Advanced or Metastatic Non-small Cell Lung Cancer Patients Treated with Pembrolizumab: A Meta-analysis. [2020]

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

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. [2022]

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

A Rare Case of Pembrolizumab-Associated Graves' Disease. [2023]

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

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. [2022]