Lenvatinib + Pembrolizumab + TACE for Liver Cancer

Recruiting at 213 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

450 Participants Needed

Trial Summary

What is the purpose of this trial?

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 (IV) placebos in participants with incurable, non-metastatic hepatocellular carcinoma (HCC). The primary hypotheses are that pembrolizumab plus lenvatinib in combination with TACE is superior to placebo plus TACE with respect to progression-free survival (PFS) and overall survival (OS).

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.

What data supports the effectiveness of the treatment Lenvatinib + Pembrolizumab + TACE for liver cancer?

Research shows that combining lenvatinib with pembrolizumab and TACE has promising effects on treating unresectable liver cancer, suggesting it could be effective for patients who cannot have surgery. ^{1 2 3 4 5}

What makes the Lenvatinib, Pembrolizumab, and TACE treatment unique for liver cancer?

This treatment is unique because it combines Lenvatinib, a drug that targets cancer growth, with Pembrolizumab, an immune system booster, and TACE, a procedure that delivers chemotherapy directly to the liver, offering a novel approach for patients with liver cancer that cannot be surgically removed. ^{1 3 5 6 7}

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Lenvatinib plus pembrolizumab for systemic therapy-naïve and -experienced unresectable hepatocellular carcinoma. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy and safety of transarterial chemoembolization combined with lenvatinib and camrelizumab in patients with BCLC-defined stage C hepatocellular carcinoma. [2023]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Safety and efficacy of lenvatinib combined with camrelizumab plus transcatheter arterial chemoembolization for unresectable hepatocellular carcinoma: A two-center retrospective study. [2022]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Lenvatinib Combined with Anti-PD-1 Antibodies Plus Transcatheter Arterial Chemoembolization for Unresectable Hepatocellular Carcinoma: A Multicenter Retrospective Study. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Transarterial Chemoembolization Combined With Lenvatinib Plus PD-1 Inhibitor for Advanced Hepatocellular Carcinoma: A Retrospective Cohort Study. [2022]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of TACE Combined with Lenvatinib and PD-(L)1 Inhibitor in the Treatment of Unresectable Hepatocellular Carcinoma: A Retrospective Study. [2023]

7. Germany pubmed.ncbi.nlm.nih.gov

Efficacy and safety of transarterial chemoembolization plus lenvatinib with or without programmed death-1 inhibitors in the treatment of unresectable hepatocellular carcinoma: a systematic review and meta-analysis. [2023]