Lenvatinib + Pembrolizumab for Advanced Thyroid Cancer

Overseen by Maria E. Cabanillas, M.D.

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Waitlist Available

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Antihypertensives, Immunosuppressants, Corticosteroids, others

Disqualifiers: Uncontrolled hypertension, Cardiovascular impairment, Autoimmune disease, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This phase II trial studies how well lenvatinib and pembrolizumab work in treating patients with anaplastic thyroid cancer that is stage IVB and has spread to nearby tissue or lymph nodes (locally advanced) and cannot be removed by surgery (unresectable), or stage IVC that has spread to other places in the body (metastatic). Lenvatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. 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. Given lenvatinib and pembrolizumab may work better than giving either one alone in treating stage IVB or C anaplastic thyroid cancer.

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 on certain treatments like chemotherapy or anti-angiogenic therapy, you may need to stop them before starting the trial. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug combination Lenvatinib and Pembrolizumab for advanced thyroid cancer?

Lenvatinib has shown effectiveness in treating advanced thyroid cancer by improving progression-free survival and response rates in patients whose cancer does not respond to radioactive iodine. Combining Lenvatinib with Pembrolizumab, a PD-1 inhibitor, has shown promising results in early reports for treating aggressive forms of thyroid cancer. ^{1 2 3 4 5}

Is the combination of Lenvatinib and Pembrolizumab safe for treating advanced thyroid cancer?

Lenvatinib and Pembrolizumab have been studied for safety in treating advanced thyroid cancer. Lenvatinib can cause side effects similar to other cancer drugs, and careful management is needed to handle these. The combination with Pembrolizumab is emerging as a treatment option, and while some safety data exists, more research is needed to fully understand its safety profile. ^{1 2 5 6 7}

How is the drug combination of Lenvatinib and Pembrolizumab unique for advanced thyroid cancer?

The combination of Lenvatinib and Pembrolizumab is unique because it pairs a multi-tyrosine kinase inhibitor (Lenvatinib) with an immune checkpoint inhibitor (Pembrolizumab), potentially enhancing treatment effectiveness for aggressive thyroid cancers like anaplastic thyroid carcinoma, which have limited options and poor prognosis. ^{1 2 3 4 7}

Research Team

Maria E. Cabanillas, M.D.

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for adults with advanced anaplastic thyroid cancer that's either spread to nearby areas and can't be surgically removed, or has metastasized. Participants need functioning major organs, no recent surgeries, controlled blood pressure without intense medication, and no severe heart issues. They must not have had chemotherapy within the last week or suffer from unmanaged autoimmune diseases. Pregnant or breastfeeding women are excluded.

Inclusion Criteria

My thyroid cancer diagnosis includes specific aggressive features.

I am willing to have tumor biopsies before and after treatment, unless my doctor advises against it.

The participant (or legally acceptable representative if applicable) provides written informed consent for the trial

Exclusion Criteria

You have had a severe allergic reaction to pembrolizumab or any of the substances it contains.

Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial

I haven't needed systemic treatment for an autoimmune disease in the last 2 years.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab IV on day 1 and lenvatinib PO daily on days 1-21, repeating every 3 weeks for up to 35 cycles

Up to 105 weeks

1 visit every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years every 3 months, then 2 years every 6 months, then annually

Regular follow-up visits

Treatment Details

Interventions

• Lenvatinib (Tyrosine Kinase Inhibitor)
• Pembrolizumab (PD-1 Inhibitor)

Trial Overview The study tests a combination of lenvatinib (which may halt tumor growth by blocking enzymes needed for cell growth) and pembrolizumab (an immunotherapy drug that might help the immune system fight cancer). The goal is to see if this combo works better than each drug alone in treating stage IVB/C anaplastic thyroid cancer.

Participant Groups

Group I: Treatment (pembrolizumab, lenvatinib) Experimental Treatment 2 Interventions

Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 3 weeks for up to 35 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive lenvatinib PO daily on days 1-21. Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Dr. Peter WT Pisters

M.D. Anderson Cancer Center

Chief Executive Officer since 2017

MD from University of Western Ontario

Dr. Jeffrey E. Lee

M.D. Anderson Cancer Center

Chief Medical Officer

MD from Stanford University School of Medicine

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School

Findings from Research

In a Phase 3 study involving 392 patients with radioiodine-refractory differentiated thyroid cancer, lenvatinib treatment resulted in a median tumor size reduction of 42.9%, with responders experiencing an even greater reduction of 51.9%.

The initial assessment at 8 weeks showed a rapid tumor size decline of 24.7%, followed by a slower continuous shrinkage, indicating that early tumor response may be a predictor of longer progression-free survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization of Tumor Size Changes Over Time From the Phase 3 Study of Lenvatinib in Thyroid Cancer. Robinson, B., Schlumberger, M., Wirth, LJ., et al.[2019]

Lenvatinib is effective for treating advanced thyroid cancer but can cause significant side effects like hypertension, diarrhea, and weight loss, which require careful management and monitoring.

Guidelines recommend proactive management strategies, including regular blood pressure checks and treatment breaks for adverse events, to help patients maintain optimal dosing while minimizing side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expert Consensus on the Management of Adverse Events During Treatment with Lenvatinib for Thyroid Cancer. Reed, N., Glen, H., Gerrard, G., et al.[2021]

Lenvatinib, a small-molecule tyrosine kinase inhibitor, has shown significant efficacy in treating advanced radioactive iodine-refractory differentiated thyroid cancer (DTC), achieving a 65% overall response rate and a median progression-free survival of 18.3 months in a phase III trial.

The drug works by targeting multiple receptors involved in tumor growth and blood vessel formation, and while it is effective, it is associated with common side effects such as hypertension and fatigue, affecting more than 50% of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenvatinib: Role in thyroid cancer and other solid tumors. Cabanillas, ME., Habra, MA.[2017]

In a study of 140 thyroid carcinoma samples, high PD-L1 expression was found in 42% of anaplastic thyroid carcinoma (ATC) cases, suggesting that immune checkpoint inhibitors like pembrolizumab could be effective for these patients.

The low expression of FGFR in thyroid tumor cells indicates that while lenvatinib (a FGFR-targeting drug) alone may not be effective, its combination with pembrolizumab may enhance treatment efficacy through immune modulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FGF-Receptors and PD-L1 in Anaplastic and Poorly Differentiated Thyroid Cancer: Evaluation of the Preclinical Rationale. Adam, P., Kircher, S., Sbiera, I., et al.[2022]

In a study of 23 patients with advanced thyroid cancer treated with lenvatinib over a median of 23 months, the treatment demonstrated long-term safety and efficacy, with a median progression-free survival of 25 months and overall survival of 46 months.

Most patients (21 out of 23) received lenvatinib as their first-line therapy, and while some experienced serious adverse events leading to treatment discontinuation, no drug-related deaths occurred, indicating that lenvatinib can be safely managed even in cases of slowly progressive disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term management of lenvatinib-treated thyroid cancer patients: a real-life experience at a single institution. Porcelli, T., Luongo, C., Sessa, F., et al.[2021]

References

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

Characterization of Tumor Size Changes Over Time From the Phase 3 Study of Lenvatinib in Thyroid Cancer. [2019]

2. England pubmed.ncbi.nlm.nih.gov

Expert Consensus on the Management of Adverse Events During Treatment with Lenvatinib for Thyroid Cancer. [2021]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Lenvatinib: Role in thyroid cancer and other solid tumors. [2017]

4. Switzerland pubmed.ncbi.nlm.nih.gov

FGF-Receptors and PD-L1 in Anaplastic and Poorly Differentiated Thyroid Cancer: Evaluation of the Preclinical Rationale. [2022]

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

Long-term management of lenvatinib-treated thyroid cancer patients: a real-life experience at a single institution. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Optimal use of lenvatinib in the treatment of advanced thyroid cancer. [2023]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Rationale Efficacy and Safety Evidence of Lenvatinib and Pembrolizumab Association in Anaplastic Thyroid Carcinoma. [2023]