Pembrolizumab and Lenvatinib for Resectable Hepatocellular Carcinoma

NCT05389527 | Active Not Recruiting Phase 2

• 1 other identifier: NeoLeap-HCC
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 4

Brief Summary

This is an open-label, multi-center, single-arm, phase II study to evaluate the efficacy and safety of lenvatinib in combination with pembrolizumab as a neoadjuvant therapy in subjects with resectable hepatocellular carcinoma (HCC).

Conditions

Carcinoma, Hepatocellular

Keywords

Hepatocellular carcinoma; Neoadjuvant therapy; Pembrolizumab; Lenvatinib

Outcome Measures

Primary Outcomes (1)

• Major pathological response (MPR)

  Defined as ≤ 50% viable tumor cells pathologically in the resected specimen.

  up to 24 weeks

Secondary Outcomes (7)

• Pathologic complete response (pCR)

  up to 24 weeks

• Objective response rate (ORR)

  up to 24 weeks

• R0 resection rate

  up to 24 weeks

• Disease-free survival (DFS)

  up to 2 years

• 1-year DFS rate

  up to 2 years

Study Arms (1)

experimental arm

EXPERIMENTAL

Pembrolizumab+Lenvatinib

Drug: Pembrolizumab+Lenvatinib

Interventions

Pembrolizumab+Lenvatinib DRUG

After enrollment, subjects receive pembrolizumab 200 mg via IV infusion on Day 1 of each 3-week cycle for 9 weeks: Lenvatinib 8 mg (body weight \<60 kg) or 12 mg (body weight ≥60 kg) orally once daily for 9 weeks. Subjects conduct surgery 1 week after the last dose of Lenvatinib. 4 weeks after surgery, Pembrolizumab and Lenvatinib will restart as adjuvant treatment for up to 1 year.

experimental arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male/female participants who are at least 18 years of age on the day of signing informed consent with histologically/cytologically or clinically (according to American Association for the Study of Liver Diseases (AASLD) criteria) confirmed diagnosis of HCC, excluding fibrolamellar sarcomatoid or mixed cholangiocarcinoma-hepatocellular carcinoma.
• Have not received any locoregional or systemic treatment before enrolment. Patients had recurrence for more than 2 years after the previous surgery could be included.
• Tumor within Milan criteria should be accompanied with microvascular invasion (judged by radionics nomogram of Fudan Zhongshan Hosp); Or beyond Milan criteria without extrahepatic metastasis.
• Resectable disease as judged by a multidisciplinary treatment group.
• Child-Pugh A.
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 to 1 and performed within 7 days prior to date of enrolment.
• In case of hepatitis B virus (HBV) positive (HBsAg (+)) subjects:
• HBV DNA \< 2000 IU/mL within 28 days before treatment; subjects received anti-HBV therapy should stay on the same therapy throughout study treatment.
• Subjects with HBV DNA \> 2000 IU/mL without anti-HBV therapy, should receive anti-HBV therapy and stay the same therapy throughout study treatment, and 2 days before treatment, the HBV DNA should decrease for at least 1 log.
• Subjects with HBV DNA \> 2000 IU/mL with anti-HBV therapy, should receive anti-HBV therapy and stay the same therapy throughout study treatment, and 2 days before treatment, the HBV DNA should decrease at least 1 log.
• Adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP ≤150/90 mmHg at Screening and no change in antihypertensive medications within 1 week prior to the treatment.
• Have measurable disease based on RECIST 1.1.
• Have adequate organ function. Specimens collected within 7 days prior to start of study treatment.
• Male participants: A male participant must agree to use a contraception of this protocol during the treatment period and for at least 120 days after the last dose of study treatment and refrain from donating sperm during this period.
• Female participants: A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:

You may not qualify if:

• Imaging findings for HCC of clear invasion into the bile duct or portal vein invasion with Vp4.
• Positive pregnancy test in female patients with childbearing potential within 72 hours prior to enrollment.
• Prior anticancer treatment or any investigational agent.
• Subjects having ≥2+ proteinuria on urinalysis will undergo 24-hour urine collection for quantitative assessment of proteinuria. Subjects with urine protein ≥1 g/24-hour will be ineligible.
• Gastrointestinal malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of lenvatinib.
• New York Heart Association congestive heart failure of grade II or above, unstable angina, myocardial infarction within the past 6 months, or serious cardiac arrhythmia associated with significant cardiovascular impairment within the past 6 months.
• Prolongation of corrected QT (QTc , Fridericia formula) interval to \>480 ms.
• Gastrointestinal bleeding event or active hemoptysis (bright red blood of at least 0.5 teaspoon) within 3 weeks prior to the first dose of study drug.
• Bleeding or thrombotic disorders or use of factor X inhibitors or anticoagulants requiring therapeutic international normalized ratio (INR) monitoring, eg, warfarin or similar agents. Treatment with low molecular weight heparin is permitted. Antiplatelet agents are prohibited throughout the study.
• Known additional malignancy that is progressing or has required active treatment within the past 3 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin or carcinoma in situ, excluding carcinoma in situ of the bladder, that have undergone potentially curative therapy are not excluded.
• Subject is known to be positive for Human Immunodeficiency Virus (HIV).
• Serious nonhealing wound, ulcer, or bone fracture.
• History of solid organ or hematologic transplant.
• Any medical or other condition which, in the opinion of the investigator, would preclude participation in a clinical trial.
• Active, known or suspected autoimmune disease that has required systemic treatment in the past 2 years or a documented history of clinically severe autoimmune disease, or any other syndrome that requires systemic steroids or immunosuppressive agents, patients with hypothyroidism stable on hormone replacement, or type 1 diabetes on insulin replacement will not be excluded from the study.

Sponsors & Collaborators

• Shanghai Zhongshan Hospital: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (4)

Zhongshan hospital

Shanghai, Shanghai Municipality, 200032, China

Location

Eastern Hepatobiliary Surgery Hospital

Shanghai, Shanghai Municipality, China

Location

Ruijin Hospital

Shanghai, Shanghai Municipality, China

Location

The first affiliated hospital, Yat-sen university

Guangzhou, China

Location

Related Publications (3)

• Bruix J, Sherman M; American Association for the Study of Liver Diseases. Management of hepatocellular carcinoma: an update. Hepatology. 2011 Mar;53(3):1020-2. doi: 10.1002/hep.24199. No abstract available.

  PMID: 21374666 RESULT

• Finn RS, Ikeda M, Zhu AX, Sung MW, Baron AD, Kudo M, Okusaka T, Kobayashi M, Kumada H, Kaneko S, Pracht M, Mamontov K, Meyer T, Kubota T, Dutcus CE, Saito K, Siegel AB, Dubrovsky L, Mody K, Llovet JM. Phase Ib Study of Lenvatinib Plus Pembrolizumab in Patients With Unresectable Hepatocellular Carcinoma. J Clin Oncol. 2020 Sep 10;38(26):2960-2970. doi: 10.1200/JCO.20.00808. Epub 2020 Jul 27.

  PMID: 32716739 RESULT

• Pinato DJ, Fessas P, Sapisochin G, Marron TU. Perspectives on the Neoadjuvant Use of Immunotherapy in Hepatocellular Carcinoma. Hepatology. 2021 Jul;74(1):483-490. doi: 10.1002/hep.31697. Epub 2021 Jun 28. No abstract available.

  PMID: 33369758 RESULT

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Officials

• Huichuan Sun

  Fudan University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Surgery

Study Record Dates

• First Submitted: May 20, 2022
• First Posted: May 25, 2022
• Study Start: September 30, 2022
• Primary Completion: December 15, 2023
• Study Completion: July 31, 2025
• Last Updated: July 11, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (4)