Lenvatinib + Pembrolizumab + TACE for Liver Cancer

Not currently recruiting at 271 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Merck Sharp & Dohme LLC

Disqualifiers: Liver transplant candidate, Gastric bleeding, Ascites, Cardiovascular impairment, 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: 6

Duration: Up to 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for liver cancer that surgery cannot cure. Researchers aim to determine if lenvatinib (a targeted therapy) and pembrolizumab (an immunotherapy), combined with TACE (a procedure that targets the liver directly), help patients live longer and prevent cancer progression compared to TACE with placebos. It targets individuals with liver cancer confined to the liver who are not eligible for a liver transplant. Participants should have controlled blood pressure and must have completed any Hepatitis C treatment at least a month before starting the trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that participants must have adequately controlled blood pressure, which may involve continuing antihypertensive medications.

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

Research has shown that using lenvatinib, pembrolizumab, and TACE (a liver cancer treatment) together is generally safe. Earlier studies demonstrated that this combination helped patients live longer without their cancer worsening. These studies assessed both the treatment's effectiveness and safety.

Patients tolerated the treatment well, with no unexpected safety issues. Lenvatinib and pembrolizumab have been used in other cancer treatments, which supports confidence in their safety. However, like most cancer treatments, some side effects occurred. Common ones included fatigue and high blood pressure, but these were usually manageable.

Overall, this treatment combination has shown promise in being both effective and safe for people with liver cancer. ^{1 2 3 4 5}

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

Researchers are excited about the combination of lenvatinib, pembrolizumab, and TACE for liver cancer because it offers a multi-faceted approach that could enhance treatment effectiveness. Lenvatinib targets and inhibits proteins involved in tumor growth, while pembrolizumab is an immunotherapy that helps the immune system recognize and attack cancer cells. TACE, which delivers chemotherapy directly to the liver tumor, complements these by cutting off the tumor's blood supply. Unlike standard treatments that might focus on a single pathway, this combination addresses the cancer from different angles, potentially leading to better outcomes for patients.

What evidence suggests that lenvatinib, pembrolizumab, and TACE could be effective for liver cancer?

In this trial, participants will receive either a combination of lenvatinib, pembrolizumab, and TACE or a placebo with TACE. Research has shown that combining lenvatinib, pembrolizumab, and TACE holds promise for treating liver cancer. Studies have found that this combination reduces the risk of cancer progression or death by 34% compared to TACE alone. It also extends the time patients live without cancer worsening. This treatment uses lenvatinib to target cancer growth, pembrolizumab to boost the immune system, and TACE to cut off the tumor's blood supply. This combined approach appears more effective than TACE alone. ^{1 2 3 5 6}

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 non-metastatic, incurable liver cancer (HCC) confirmed by radiology or pathology. Eligible participants may have had Hepatitis B or C if treated properly. They must have stable blood pressure and organ function, and their cancer should be limited to the liver but not suitable for curative treatment.

Inclusion Criteria

My liver cancer cannot be cured with surgery or other treatments.

My organs are functioning well.

My blood pressure is under control, with or without medication.

Exclusion Criteria

I have a serious wound or broken bone that isn't healing.

I haven't had major heart problems like heart failure in the last year.

I have had treatment directly on liver tumors.

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 in combination with TACE or placebo plus TACE

Up to 2 years

Pembrolizumab IV every 6 weeks, lenvatinib daily

Follow-up

Participants are monitored for progression-free survival and overall survival

Up to 43 months

Long-term Follow-up

Participants are monitored for disease control rate and adverse events

Up to 95 months

What Are the Treatments Tested in This Trial?

Interventions

• Lenvatinib
• Pembrolizumab
• TACE

Trial Overview

The study tests the effectiveness of lenvatinib plus pembrolizumab with TACE against placebo plus TACE in improving survival without cancer progression in patients with HCC. The goal is to see if combining these drugs with TACE leads to better outcomes than TACE alone.

How Is the Trial Designed?

Group I: Lenvatinib plus Pembrolizumab plus TACE Experimental Treatment 3 Interventions

Participants will receive a combination of lenvatinib, pembrolizumab, and TACE. Lenvatinib will be administered at a dose of 12 mg (for participants with screening body weight ≥60 kg) or 8 mg (for participants with screening body weight \<60 kg) orally once a day during each 21-day cycle until progressive disease or unacceptable toxicity (up to 2 years \[\~35 cycles\] or longer with Sponsor approval). Pembrolizumab will be administered via IV infusion at a dose of 400 mg once every 6 weeks (Q6W) for up to 2 years (\~17 doses). Participants will undergo TACE as a background procedure of chemotherapeutic and embolic agent(s).

Group II: Oral Placebo plus IV Placebo plus TACE Active Control 3 Interventions

Participants will receive a combination of lenvatinib-matching oral placebo, pembrolizumab-matching IV placebo, and TACE. Lenvatinib-matching oral placebo will be administered once a day during each 21-day cycle for up to 2 years (\~35 cycles) or longer with Sponsor approval and pembrolizumab-matching IV placebo will be administered once every 6 weeks (Q6W) for up to 2 years (\~17 doses). Participants will undergo TACE as a background procedure of chemotherapeutic and embolic agent(s).

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 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

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

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

In a study of 71 patients with unresectable hepatocellular carcinoma (uHCC), the combination of lenvatinib and pembrolizumab demonstrated a high disease control rate of 84.1% for first-line treatment, indicating its efficacy in managing this condition.

The treatment did not adversely affect liver function, as measured by the Albumin-Bilirubin (ALBI) score, and factors such as prior nivolumab failure and Child-Pugh class B were associated with poorer progression-free and overall survival, highlighting the need for further investigation in these subgroups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenvatinib plus pembrolizumab for systemic therapy-naïve and -experienced unresectable hepatocellular carcinoma. Wu, CJ., Lee, PC., Hung, YW., et al.[2022]

In a study of 62 patients with unresectable hepatocellular carcinoma (uHCC), the combination of lenvatinib, anti-PD-1 antibodies, and transcatheter arterial chemoembolization (TACE) resulted in a high objective response rate of approximately 80%, indicating strong efficacy in shrinking tumors.

Over half of the patients (53.2%) became eligible for surgical resection after treatment, demonstrating the potential of this triple therapy to convert previously unresectable tumors into resectable ones, with manageable side effects reported in 74.2% of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenvatinib Combined with Anti-PD-1 Antibodies Plus Transcatheter Arterial Chemoembolization for Unresectable Hepatocellular Carcinoma: A Multicenter Retrospective Study. Wu, JY., Yin, ZY., Bai, YN., et al.[2022]

Citations

1.

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 ...

The five-year relative survival rate for liver cancer in the U.S. is 22% based on Surveillance, Epidemiology, and End Results (SEER) data from ...

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11936454/

Lenvatinib plus Pembrolizumab Combined with Transarterial ...

The combination of lenvatinib (LEN), pembrolizumab (PEM), and transarterial chemoembolization (TACE) (LEN-PEM-TACE) was found to prolong ...

3.

eisai.com

eisai.com/news/2024/news202466.html

LENVIMA® (lenvatinib) Plus KEYTRUDA® ...

LENVIMA plus KEYTRUDA in combination with TACE reduced the risk of disease progression or death by 34% compared to TACE alone.

4.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04246177

NCT04246177 | Safety and Efficacy of Lenvatinib (E7080/ ...

The purpose of this study is to evaluate the efficacy and safety of lenvatinib and pembrolizumab in combination with TACE versus TACE plus oral and ...

5.

thelancet.com

thelancet.com/journals/lancet/article/PIIS0140-6736(24)02575-3/abstract

Transarterial chemoembolisation combined with lenvatinib ...

TACE plus lenvatinib plus pembrolizumab showed significant, clinically meaningful improvement in progression-free survival in patients with unresectable, non- ...

6.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04246177

NCT04246177 | Safety and Efficacy of Lenvatinib (E7080/ ...

The purpose of this study is to evaluate the efficacy and safety of lenvatinib and pembrolizumab in combination with TACE versus TACE plus oral and intravenous ...