Lenvatinib + Pembrolizumab for Head and Neck Cancer

Not currently recruiting at 154 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Merck Sharp & Dohme Corp.

Must not be taking: Steroids, Immunosuppressants

Disqualifiers: CNS metastases, Autoimmune disease, HIV, 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: Unknown

Duration: Up to 3 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two drugs, lenvatinib and pembrolizumab, to determine if they can extend the lives of people with head and neck cancer. It targets individuals whose cancer has returned or spread after previous treatments. The trial compares this drug combination to standard chemotherapy. Candidates may qualify if their head and neck cancer has worsened after treatments with platinum-based drugs and immunotherapy. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you should discuss your current medications with the study team to ensure they don't interfere with the trial treatments.

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

Research has shown that using lenvatinib and pembrolizumab together yields promising results for treating cancer. In some studies, patients experienced significant improvements in symptoms and quality of life over extended treatment periods. However, results are mixed; while patients often had longer periods without disease progression, overall survival did not always increase.

This combination treatment has been linked to serious side effects. Approximately 67% of patients experienced severe side effects, leading some to discontinue treatment early.

When lenvatinib is used alone, studies on other cancer types have found heart-related issues in about 3% of patients. In head and neck cancer, some patients experienced serious side effects, with many discontinuing treatment as a result.

Discussing these potential risks and benefits with a healthcare provider is crucial when considering joining a clinical trial. ^{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 head and neck cancer because this duo offers a novel approach compared to standard chemotherapy options like docetaxel, paclitaxel, cetuximab, or capecitabine. Lenvatinib, an oral medication, inhibits multiple proteins that promote cancer cell growth, while pembrolizumab, an immune checkpoint inhibitor given intravenously, enhances the body's immune response against cancer cells. This combination targets cancer more directly and may offer a more effective treatment with potentially fewer side effects, setting it apart from traditional chemotherapy regimens.

What evidence suggests that this trial's treatments could be effective for head and neck cancer?

Research shows that combining lenvatinib and pembrolizumab may help treat certain types of recurring or spreading head and neck cancer. In this trial, participants will receive either the combination of lenvatinib and pembrolizumab, lenvatinib alone, or standard of care (SOC) chemotherapy. Some studies found that the lenvatinib and pembrolizumab combination helped more patients by shrinking their tumors or stopping them from growing. However, results on overall survival have been mixed. While it helped patients live longer without disease progression, it didn't always extend overall survival compared to other treatments. Despite these mixed results, this combination still offers a possible option for patients with few other choices. ^{2 4 5 6 7}

Who Is on the Research Team?

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Are You a Good Fit for This Trial?

This trial is for adults with recurrent/metastatic head and neck squamous cell carcinoma that worsened after platinum therapy and anti-PD-1/PD-L1 treatment. Participants must have measurable disease, be in good physical condition (ECOG 0 or 1), agree to use contraception, and not have other active cancers or severe health conditions.

Inclusion Criteria

Pre-study imaging showing disease progression per RECIST 1.1 criteria

Measurable disease by CT or MRI per RECIST 1.1 criteria

Female participants must not be pregnant or breastfeeding, meet contraceptive criteria, and agree not to donate or freeze/store eggs

Exclusion Criteria

I have undergone 4 or more treatments for my recurring or spreading cancer.

I have received an organ or tissue transplant from another person.

My condition can be treated with the aim of curing it.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive lenvatinib and pembrolizumab or standard chemotherapy until disease progression or discontinuation criteria are met

Up to 3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Capecitabine
• Cetuximab
• Docetaxel
• Lenvatinib
• Paclitaxel
• Pembrolizumab

Trial Overview The study tests lenvatinib combined with pembrolizumab against standard chemotherapy, and also lenvatinib alone. It aims to see if the combination is more effective based on tumor response rates. Patients are randomly assigned to these treatments.

How Is the Trial Designed?

Group I: Lenvatinib + Pembrolizumab Experimental Treatment 2 Interventions

Participants will be treated with the combination of lenvatinib (once daily 20 mg oral dose) plus pembrolizumab (200 mg 30-minute intravenous (IV) infusion on Day 1 of each 21-day cycle for 35 cycles), until centrally verified disease progression, or until a protocol-specified discontinuation criterion is met. Participants may receive up to an additional 17 cycles of pembrolizumab as Second Course treatment, with or without lenvatinib.

Group II: Lenvatinib Monotherapy Active Control 1 Intervention

Participants will be treated with lenvatinib monotherapy (once daily 24 mg oral dose) until centrally verified disease progression, or until a protocol-specified discontinuation criterion is met.

Group III: SOC Chemotherapy Active Control 4 Interventions

Participants will be treated with investigator's choice of standard of care (SOC) chemotherapy (docetaxel, paclitaxel, cetuximab, or capecitabine) until centrally verified disease progression, or until a protocol-specified discontinuation criterion is met.

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?

Merck Sharp & Dohme Corp.

Lead Sponsor

Trials

2,287

Recruited

4,582,000+

Chirfi Guindo

Merck Sharp & Dohme Corp.

Chief Medical Officer

Engineering degree from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme Corp.

Chief Executive Officer since 2021

J.D. from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Merck Sharp & Dohme LLC

Lead 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

Eisai Inc.

Industry Sponsor

Trials

524

Recruited

161,000+

Founded

Eisai Inc. was established in 1995 as the U.S. subsidiary of Eisai Co., Ltd.

Headquarters

Woodcliff Lake, NJ, USA

Known For

Neurology and Oncology

Top Products

Aricept (donepezil), Lenvima (lenvatinib), Leqembi (lecanemab), Halaven (eribulin)

Lynn Kramer

Eisai Inc.

Chief Medical Officer since 2019

MD

Tatsuyuki Yasuno

Eisai Inc.

Chief Executive Officer since 2023

MBA from Kellogg School of Management, Northwestern University; Bachelor of Political Science from Waseda University

Published Research Related to This Trial

The combination of lenvatinib, a multikinase inhibitor, and pembrolizumab, a PD-1 inhibitor, shows promising antitumor activity and durable responses in various solid tumors, as indicated by preliminary results from the LEAP clinical trial program.

This combination therapy has a manageable safety profile, suggesting it could be a valuable new treatment option for solid cancers that currently have limited therapeutic alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The LEAP program: lenvatinib plus pembrolizumab for the treatment of advanced solid tumors. Taylor, MH., Schmidt, EV., Dutcus, C., et al.[2021]

In a study of adult patients with metastatic head and neck squamous cell cancer, substituting 5-fluorouracil (5-FU) with a taxane in a pembrolizumab-based treatment regimen did not increase toxicity or worsen survival outcomes.

Patients receiving the taxane combination experienced significantly lower rates of mucositis and elevated creatinine levels compared to those on the 5-FU regimen, indicating a better safety profile for the taxane approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety outcomes of pembrolizumab with platinum agent chemotherapy combined with 5-fluorouracil or taxane derivative in head and neck cancer. Lee, B., Chehab, SS., Fan, W., et al.[2023]

In a study of 14 heavily pretreated patients with recurrent and metastatic head and neck squamous cell carcinoma (R/M HNSCC), the combination of pembrolizumab and lenvatinib showed an objective response rate of 28.6%, indicating potential efficacy even in patients who had previously failed anti-PD-1 therapy.

The disease control rate was 42.9%, with an overall survival of 6.2 months and progression-free survival of 4.6 months, suggesting that this combination therapy may provide meaningful benefits for patients who have limited treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination of pembrolizumab and lenvatinib is a potential treatment option for heavily pretreated recurrent and metastatic head and neck cancer. Chen, TH., Chang, PM., Yang, MH.[2021]

In the CLEAR study involving 352 patients, the combination of lenvatinib and pembrolizumab showed a manageable safety profile, with common adverse reactions including fatigue (63.1%), diarrhea (61.9%), and hypertension (56.3%).

Most adverse reactions occurred within approximately 5 months of starting treatment, and effective management strategies such as monitoring and dose modifications were identified to ensure patient safety and support ongoing treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization and Management of Adverse Reactions From the CLEAR Study in Advanced Renal Cell Carcinoma Treated With Lenvatinib Plus Pembrolizumab. Motzer, R., George, S., Merchan, JR., et al.[2023]

The combination of pembrolizumab and lenvatinib demonstrated significantly higher objective response rates (ORRs) and progression-free survival (mPFS) compared to their individual therapies in solid cancers, with ORRs reaching up to 70% in renal cell carcinoma.

Despite a high incidence of adverse events (68.0% for the combination therapy), the toxicities were manageable and no unexpected safety issues were reported, indicating that the combination therapy is both effective and relatively safe.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of pembrolizumab plus lenvatinib versus pembrolizumab and lenvatinib monotherapies in cancers: A systematic review. Mo, DC., Luo, PH., Huang, SX., et al.[2021]

Pembrolizumab (KEYTRUDA) received accelerated FDA approval for treating recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) based on a study of 174 patients, showing an objective response rate of 16% and a duration of response ranging from 2.4 to 27.7 months.

The safety profile included serious adverse reactions such as pneumonia and respiratory failure, but the overall benefit-risk assessment was deemed acceptable, marking pembrolizumab as the first new treatment option for HNSCC since 2006.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma with Disease Progression on or After Platinum-Containing Chemotherapy. Larkins, E., Blumenthal, GM., Yuan, W., et al.[2019]

In a phase 2 trial involving 29 patients with advanced gastric cancer, the combination of lenvatinib and pembrolizumab resulted in a promising objective response rate of 69%, indicating significant anti-tumor activity.

The treatment was generally well-tolerated, with the most common grade 3 adverse events being manageable, such as hypertension and proteinuria, and no serious treatment-related complications or deaths reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenvatinib plus pembrolizumab in patients with advanced gastric cancer in the first-line or second-line setting (EPOC1706): an open-label, single-arm, phase 2 trial. Kawazoe, A., Fukuoka, S., Nakamura, Y., et al.[2020]

The combination of lenvatinib and pembrolizumab shows significant clinical benefits for patients with endometrial carcinoma, with a safety profile consistent with each drug's individual use, primarily involving manageable side effects like hypertension and hypothyroidism.

Effective management of lenvatinib's common adverse events is crucial to maximize its efficacy, as most side effects can be prevented or mitigated through proactive monitoring and intervention during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimizing the use of lenvatinib in combination with pembrolizumab in patients with advanced endometrial carcinoma. Lorusso, D., Danesi, R., Locati, LD., et al.[2023]

Pembrolizumab, an immune checkpoint inhibitor, has been approved by the FDA for treating platinum-refractory recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC), offering a new option with potentially improved efficacy compared to traditional chemotherapy and EGFR inhibitors.

This review discusses the pharmacology and tolerability of pembrolizumab, emphasizing its mechanism of action by blocking the PD-1 receptor, which may enhance the immune response against HNSCC tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab and its use in the treatment of recurrent or metastatic head and neck cancer. Sheth, S., Weiss, J.[2019]

In a phase 3 study involving 495 patients with recurrent or metastatic head-and-neck squamous cell carcinoma, pembrolizumab demonstrated a median overall survival of 8.4 months, compared to 6.9 months for standard-of-care treatments, indicating a significant improvement in survival rates.

Pembrolizumab was associated with fewer severe treatment-related adverse events (13%) compared to standard-of-care therapies (36%), suggesting a better safety profile for patients receiving pembrolizumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus methotrexate, docetaxel, or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma (KEYNOTE-040): a randomised, open-label, phase 3 study. Cohen, EEW., Soulières, D., Le Tourneau, C., et al.[2019]

Citations

1. merck.com merck.com/news/merck-and-eisai-provide-update-on-phase-3-leap-010-trial-evaluating-keytruda-pembrolizumab-plus-lenvima-lenvatinib-in-patients-with-certain-types-of-recurrent-or-metastatic-head-and-ne/

Merck and Eisai Provide Update on Phase 3 LEAP-010 ... Merck and Eisai are studying the KEYTRUDA plus LENVIMA combination through the LEAP (LEnvatinib And Pembrolizumab) clinical program in various ...

2. ascopost.com ascopost.com/issues/march-25-2024/lenvatinib-plus-pembrolizumab-fails-to-improve-overall-survival-in-advanced-head-and-neck-cancer/

Lenvatinib Plus Pembrolizumab Fails to Improve Overall ... The overall response rate at 24 weeks was 46%, with a median progression-free survival of 4.7 months. “These findings reinforce pembrolizumab ...

3. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK601704/

Clinical Review - Pembrolizumab in Combination With ... - NCBI The Health Canada–approved indication of interest for this review is PEM in combination with lenvatinib (LEN) for the treatment of adult patients with advanced ...

4. journals.lww.com journals.lww.com/jcma/fulltext/2021/04000/combination_of_pembrolizumab_and_lenvatinib_is_a.5.aspx

Combination of pembrolizumab and lenvatinib is a potential... This study supported the use of pembrolizumab/lenvatinib combination therapy in R/M HNSCC patients without standard of care. 1. INTRODUCTION. The treatment of ...

5. cancernetwork.com cancernetwork.com/view/pembrolizumab-lenvatinib-combo-shows-mixed-results-in-recurrent-metastatic-hnscc

Pembrolizumab/Lenvatinib Combo Shows Mixed Results ... Combining lenvatinib (Lenvima) with pembrolizumab (Keytruda) significantly improved overall response rate (ORR) and progression-free survival (PFS) but not ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9601195/

Rationale Efficacy and Safety Evidence of Lenvatinib and ... With treatment periods ranging from 1 to 40 months, the median progression-free survival for ATCs was 16.5 months. Four patients experienced ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2020.38.15_suppl.6541

A phase I/Ib study of lenvatinib and cetuximab in patients ... Of the 9 evaluable HNSCC pts treated with lenvatinib 20mg daily, 6 pts had a PR with a 67% ORR. For the 8 pts who have completed treatment, the ...