Pembrolizumab for Thyroid Cancer

Overseen By Emmanuel Ugwu

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Stanford University

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

Disqualifiers: Immunodeficiency, Active infection, Autoimmune, 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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: Approximately 2 years

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests pembrolizumab (KEYTRUDA), administered through an IV every three weeks, to evaluate its effectiveness for individuals with anaplastic thyroid cancer who lack other treatment options. The trial targets those whose cancer has spread beyond the thyroid or cannot be surgically removed. Suitable candidates include those with confirmed anaplastic thyroid cancer who have undergone surgery or radiation but still have active disease. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, providing access to potentially effective 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, if you are taking dabrafenib, trametinib, or lenvatinib, you will need a 1-week break from these before starting the trial.

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

Research has shown that pembrolizumab is generally safe. While it can cause side effects, they are usually manageable. Common side effects include fatigue, loss of appetite, and elevated levels of the digestive enzyme lipase. In past studies, patients with advanced thyroid cancer tolerated the treatment well. Pembrolizumab has also demonstrated positive results in treating other types of thyroid cancer, suggesting it could be a safe option for those with difficult-to-treat cancer. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for thyroid cancer?

Pembrolizumab is unique because it harnesses the power of the immune system to fight thyroid cancer. Unlike traditional treatments like surgery and radioactive iodine therapy, pembrolizumab is an immunotherapy that works by targeting and blocking the PD-1 pathway. This pathway often prevents the immune system from attacking cancer cells. Researchers are excited about pembrolizumab because it offers a novel approach that could be more effective for patients, especially those who have not responded well to conventional treatments.

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

Research has shown that pembrolizumab yields promising results for treating advanced thyroid cancer. In one study, patients experienced manageable side effects and a significant decrease in tumor size. Another report found that after six months, all patients remained alive, and about 59% showed no cancer progression. This trial will evaluate pembrolizumab as a treatment option for those with limited alternatives. The treatment enhances the immune system's ability to attack cancer cells more effectively. ^{1 4 5 6 7}

Who Is on the Research Team?

Saad Khan, MD

Principal Investigator

Stanford University

Are You a Good Fit for This Trial?

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.

Ability to understand and sign the informed consent document

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab

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.

How Is the Trial Designed?

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.

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?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

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

Published Research Related to This Trial

Pembrolizumab, an immune checkpoint inhibitor, has demonstrated significant efficacy in reducing tumor size and improving survival rates in patients with non-small cell lung carcinoma (NSCLC).

However, the treatment is associated with an increased risk of immune-related adverse effects, including cases of type 1 diabetes mellitus and autoimmune thyroiditis, highlighting the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab: An Immunotherapeutic Agent Causing Endocrinopathies. Chaudry, A., Chaudry, M., Aslam, J.[2020]

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]

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 (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, 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 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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36748723/

Efficacy and safety of pembrolizumab monotherapy in ... Pembrolizumab demonstrated manageable toxicity and durable antitumor activity in a small subset of patients with advanced thyroid cancer.

2. sciencedirect.com sciencedirect.com/science/article/pii/S0305737225001641

Effectiveness of immune checkpoint inhibitor therapy in ... Most studies reported that pembrolizumab was generally well tolerated. Rates of AEs and TRAEs spanned as high as 100 % and 82 % respectively [29 ...

3. cinj.org cinj.org/fighting-advanced-thyroid-cancer-immunotherapy

Fighting Advanced Thyroid Cancer with Immunotherapy The six-month overall survival rate was 100 percent and the six month progression free survival rate was 58.7 percent. Updated results will be announced at the ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10882904/

First effectiveness data of lenvatinib and pembrolizumab as ... Here, we present real-world outcome data on the activity of the combination of lenvatinib and pembrolizumab as a systemic first-line therapy ...

5. acsjournals.onlinelibrary.wiley.com acsjournals.onlinelibrary.wiley.com/doi/full/10.1002/cncr.34657

Efficacy and safety of pembrolizumab monotherapy in patients ... Pembrolizumab demonstrated manageable toxicity and durable antitumor activity in a small subset of patients with advanced thyroid cancer. These ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/30832606/

Safety and antitumor activity of the anti-PD-1 ... - PubMed Results of this phase Ib proof-of-concept study suggest that pembrolizumab has a manageable safety profile and demonstrate evidence of antitumor activity.

7. merck.com merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf

keytruda_pi.pdf Safety data are available for the first 203 patients who received KEYTRUDA and chemotherapy (n=101) or placebo and chemotherapy (n=102). Patients with ...