Lenvatinib + Pembrolizumab for Advanced Thyroid Cancer

Overseen By Maria E Cabanillas

Age: 18+

Sex: Any

Trial Phase: Phase 2

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 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

Compensation: Varies

Number of Visits: 1

Duration: Up to 105 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two treatments, lenvatinib (a targeted therapy) and pembrolizumab (an immunotherapy), for individuals with advanced anaplastic thyroid cancer. It targets those whose cancer has spread locally or to other parts of the body and cannot be surgically removed. The trial investigates whether these treatments, which halt cancer growth and assist the immune system in fighting cancer, are more effective together. Individuals with locally advanced or metastatic anaplastic thyroid cancer, who cannot undergo surgery or radiation, might be suitable candidates for this trial. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of lenvatinib and pembrolizumab is generally well-tolerated. In studies, almost all patients experienced some side effects, but these were usually manageable. One study focusing on thyroid cancer patients found this combination to be both safe and effective. This finding reassures potential trial participants, as managing side effects is an important part of the treatment process. While side effects are common, the combination has shown promise in treating advanced cancers. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of lenvatinib and pembrolizumab for advanced thyroid cancer because it brings together two powerful cancer-fighting strategies. Lenvatinib is a tyrosine kinase inhibitor that blocks signals tumors need to grow, while pembrolizumab is an immunotherapy that helps the immune system better recognize and attack cancer cells. This dual approach targets the cancer from different angles, potentially leading to more effective results than the current standard treatments, which typically involve surgery, radioactive iodine, and standard chemotherapy. By combining these therapies, there's hope for improved outcomes and survival rates for patients with advanced thyroid cancer.

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

Research has shown that using lenvatinib and pembrolizumab together may help treat advanced thyroid cancer. In one study, patients who received this combination treatment lived an average of 17.4 months, compared to 12.0 months with other treatments. This suggests the combination can extend life expectancy. It was also effective for patients who hadn't tried other treatments before, with some experiencing significant improvements. Additionally, most people tolerate the treatment well, with generally manageable side effects. These findings suggest this combination could be a strong option for fighting advanced thyroid cancer. Participants in this trial will receive both lenvatinib and pembrolizumab as part of the treatment regimen. ^{1 3 6 7 8}

Who Is on the Research Team?

Maria E. Cabanillas, M.D.

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

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.

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

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Lenvatinib
• Pembrolizumab

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.

How Is the Trial Designed?

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.

Lenvatinib is already approved in United States, European Union for the following indications:

Approved in United States as Lenvima for:

• Differentiated Thyroid Cancer
• Renal Cell Carcinoma
• Hepatocellular Carcinoma
• Endometrial Cancer

Approved in European Union as Lenvima for:

• Thyroid Cancer
• Renal Cell Carcinoma
• Hepatocellular Carcinoma
• Endometrial Cancer

Approved in European Union as Kisplyx for:

• Renal Cell Carcinoma

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

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]

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]

Lenvatinib and pembrolizumab are emerging treatment options for anaplastic thyroid carcinoma (ATC), showing potential efficacy when used together, although most evidence comes from off-label use due to the rarity of ATC and lack of randomized controlled trials.

The review highlights the preclinical rationale for their combined use and discusses safety considerations, suggesting that this combination could improve treatment outcomes for patients with metastatic ATC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rationale Efficacy and Safety Evidence of Lenvatinib and Pembrolizumab Association in Anaplastic Thyroid Carcinoma. Boudin, L., Morvan, JB., Thariat, J., et al.[2023]

Lenvatinib, a multitargeted kinase inhibitor, has shown effectiveness in stabilizing progressive metastatic thyroid cancer and may improve overall survival, based on pivotal phase III trials.

While lenvatinib is a promising treatment option, it comes with a side-effect profile similar to other kinase inhibitors, necessitating careful monitoring and management of adverse events to maintain therapy continuity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimal use of lenvatinib in the treatment of advanced thyroid cancer. Takahashi, S., Kiyota, N., Tahara, M.[2023]

Citations

1. eisai.com eisai.com/news/2025/news202573.html

LENVIMA® (lenvatinib) Plus KEYTRUDA® ... In the primary analysis, the median OS was 17.4 months (95% CI, 14.2-19.9) for LENVIMA plus KEYTRUDA versus 12.0 months (95% CI, 10.8-13.3) for ...

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

First effectiveness data of lenvatinib and pembrolizumab as ... The combination of lenvatinib and pembrolizumab was effective and moderately tolerated in treatment-naïve ATC patients with occasional long- ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38383419/

First effectiveness data of lenvatinib and pembrolizumab as ... The median progression-free survival was 4.7 (range 0.8-5.9) months, and the median overall survival was 6.3 (range 0.8-not reached) months. At ...

4. 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 ...

5. merck.com merck.com/news/keytruda-pembrolizumab-plus-lenvima-lenvatinib-demonstrates-durable-5-year-survival-benefit-versus-chemotherapy-for-patients-with-advanced-endometrial-carcinoma-following-one-prior-pla/

KEYTRUDA® (pembrolizumab) Plus LENVIMA® ... At five years, KEYTRUDA plus LENVIMA showed a 16.7% overall survival (OS) rate for these patients with mismatch repair proficient (pMMR) advanced ...

6. eisai.com eisai.com/news/2024/news202466.html

LENVIMA® (lenvatinib) Plus KEYTRUDA® ... Treatment-related adverse events (TRAEs) occurred in 98.7% of patients receiving LENVIMA plus KEYTRUDA in combination with TACE versus 84.6% of ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04731740?term=AREA%5BInterventionSearch%5D(ER-203492-00)%20AND%20AREA%5BStudyType%5D(INTERVENTIONAL)&rank=3

Pembrolizumab and Lenvatinib/Chemotherapy for Poorly ... The aim of the study is to evaluate the efficacy of the combination of lenvatinib with pembrolizumab, and to establish a safe and effective systemic treatment ...

8. annalsofoncology.org annalsofoncology.org/article/S0923-7534(22)03577-3/fulltext

1646MO Phase II ATLEP trial: Final results for lenvatinib ... Our results implicate that a combination of lenvatinib and pembrolizumab is safe and effective in patients with ATC and PDTC, and induces high response rates.