Pembrolizumab +/− Lenvatinib for Head and Neck Cancer

(LEAP-10 Trial)

No longer recruiting at 195 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Merck Sharp & Dohme Corp.

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Cardiovascular impairment, Autoimmune disease, CNS metastases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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: 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of drugs, pembrolizumab (an immunotherapy) and lenvatinib (a targeted therapy), to determine if they work better together than pembrolizumab alone for a specific type of head and neck cancer. Researchers aim to see if this combination can improve the cancer's response to treatment, slow its progression, and extend patients' lives. Participants should have recurrent or metastatic head and neck squamous cell carcinoma that cannot be cured with local therapies, with tumors in the oropharynx, oral cavity, hypopharynx, or larynx. This trial is not suitable for those allergic to the study drugs or who have certain other medical conditions. As a Phase 3 trial, this study represents the final step before FDA approval, offering patients a chance to contribute to potentially groundbreaking treatment advancements.

Do I have to stop taking my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that you should not be on certain treatments like systemic steroids above a specific dose or have received certain therapies recently. It's best to discuss your current medications with the trial team to see if they might affect your eligibility.

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

A previous study found that almost all patients (98.7%) who took both pembrolizumab and lenvatinib experienced treatment-related side effects. This combination has been tested for other conditions and is usually well-tolerated, though side effects are common. Common issues include high blood pressure, tiredness, and diarrhea. However, some patients reported overall improvement and noticed their cancer symptoms improved. Pembrolizumab is an approved treatment for several types of cancer, so its safety is well-known. Lenvatinib is also approved for other uses. Current studies are examining how these drugs work together, especially for head and neck cancer, so understanding of their combined safety is still developing. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about pembrolizumab combined with lenvatinib for head and neck cancer because it offers a unique approach compared to standard treatments like chemotherapy and radiation. Pembrolizumab is an immunotherapy that helps the immune system target and destroy cancer cells, while lenvatinib is a targeted therapy that inhibits the growth of blood vessels feeding tumors. This combination could enhance the body's ability to fight cancer more effectively. Unlike traditional treatments that often cause significant side effects, this regimen aims to provide a more precise and potentially less toxic option.

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

Research has shown that using pembrolizumab and lenvatinib together can help patients with head and neck cancer. In this trial, one group of participants will receive this combination. Studies have found that this combination significantly increases the chance of the tumor shrinking or disappearing and delays the cancer from worsening. Specifically, one study found that 46% of patients experienced tumor shrinkage at 24 weeks, and the cancer did not worsen for an average of 4.7 months. However, this combination did not extend overall survival. These findings suggest that while the treatment may help control cancer growth, it might not increase life expectancy. Another group in this trial will receive pembrolizumab with a placebo, allowing researchers to compare the effectiveness of the combination treatment. ^{2 3 6 7 8}

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 or metastatic head and neck squamous cell carcinoma that can't be cured by surgery or radiation. They must have good organ function, not be pregnant or breastfeeding, agree to use contraception, and have a certain level of physical ability (ECOG score 0-1). People who've had recent major surgery, live vaccines, other cancer treatments like pembrolizumab or similar drugs in the past are excluded.

Inclusion Criteria

I am not pregnant, breastfeeding, and if able to bear children, I agree to use contraception as required.

Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If the contraception requirements in the local label for any of the study interventions is more stringent than the requirements above, the local label requirements are to be followed

My cancer can be measured and has grown in previously treated areas.

Exclusion Criteria

I have not had cancer treatment or been in a drug trial in the last 4 weeks.

I am currently being treated for an active infection.

I haven't had major heart problems or strokes in the last year.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab with or without lenvatinib as a first line intervention for up to 35 cycles

24 months

1 visit every 21 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

13 months

Long-term follow-up

Participants are monitored for overall survival and progression-free survival

Up to 37 months

What Are the Treatments Tested in This Trial?

Interventions

• Lenvatinib
• Pembrolizumab
• Placebo

Trial Overview The study tests if combining Pembrolizumab with Lenvatinib improves response rates, slows disease progression, and extends survival compared to Pembrolizumab with a placebo. Participants will either receive both drugs or one drug plus a placebo without knowing which group they're in.

How Is the Trial Designed?

Group I: Pembrolizumab with Lenvatinib Experimental Treatment 2 Interventions

Participants receive lenvatinib 20 mg orally once a day (QD) plus pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W). Pembrolizumab will be administered for up to 35 cycles (approximately 24 months). Lenvatinib will be administered until progressive disease or unacceptable toxicity.

Group II: Pembrolizumab with Placebo Active Control 2 Interventions

Participants receive lenvatinib-matching placebo orally once a day (QD) plus pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W). Pembrolizumab will be administered for up to 35 cycles (approximately 24 months).

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

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 ...

2. 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 ...

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. 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 ...

5. keytrudalenvima.com keytrudalenvima.com/clinical-trial-results/

Results from clinical trials with KEYTRUDA + LENVIMA View results from clinical trials with KEYTRUDA® (pembrolizumab) and LENVIMA® (lenvatinib). Select a type of cancer to see the results.

6. merck.com merck.com/news/merck-and-eisai-provide-update-on-phase-3-leap-012-trial-in-unresectable-non-metastatic-hepatocellular-carcinoma/

Merck and Eisai Provide Update on Phase 3 LEAP-012 ... As reported previously, KEYTRUDA plus LENVIMA in combination with TACE met the study's other primary endpoint of progression-free survival (PFS) ...

7. merck.com merck.com/news/keytruda-pembrolizumab-plus-lenvima-lenvatinib-combination-demonstrated-statistically-significant-improvement-in-overall-survival-progression-free-survival-and-objective-response-rate/

KEYTRUDA® (pembrolizumab) Plus LENVIMA® ... The safety profile of the KEYTRUDA plus LENVIMA combination was consistent with previously reported studies. Merck and Eisai will discuss these ...

8. 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 ...