Lenvatinib After Progression on Atezolizumab-bevacizumab in Hepatocellular Carcinoma

NCT06138769 | Active Not Recruiting Phase 2

• 1 other identifier: LENVINEXT
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Although atezolizumab-bevacizumab has been positioned as the standard first-line therapy in unresectable heptocellular carcinoma, eventually most patients progressed on this regimen. Despite of multiple drugs are approved for the management of unresectable hepatocellular carcinoma, only a few trials have been conducted to investigate their efficacy in the second-line setting after the progression on atezolizumab-bevacizumab. Lenvatinib is approved first-line multikinase inhibitor in unresectable hepatocellular carcinoma, but has not yet been investigated as second-line therapy in prospective study. In this single arm phase 2 study, the efficacy and safety of lenvatinib will be investigated for patients who progressed on first-line atezolizumab-bevacizumab.

Conditions

Hepatocellular Carcinoma

Keywords

hepatocellular carcinoma; lenvatinib; atezolizumab-bevacizumab

Outcome Measures

Primary Outcomes (1)

• Progression-free survival

  Time interval between the start of lenvatinb to the disease progression or any cause of death.

  1 year

Secondary Outcomes (4)

• Overall survival

  1 year

• Overall response rate

  1 year

• Disease control rate

  1 year

• Adverse events

  1 year

Study Arms (1)

Lenvatinib

EXPERIMENTAL

Lenvatinib 12 mg (body weight 60 kg or greater) or 8 mg (body weight \< 60 kg) once orally every day

Drug: Lenvatinib

Interventions

Lenvatinib DRUG

Lenvatinib 12 mg (body weight 60 kg or greater) or 8 mg (body weight \< 60 kg) once orally every day

Lenvatinib

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of HCC according to AASLD guidelines
• Disease that is not amenable to a curative treatment (e.g. surgery, transplant, radiofrequency ablation)
• Prior treatment with atezolizumab plus bevacizumab as first-line treatment for unresectable HCC
• Progression after atezolizumab plus bevacizumab, the duration of these treatments must be 2 consecutive treatment cycles or more.
• At least 1 RECIST v1.1 measurable untreated lesion
• Recovery to ≤ Grade 1 from toxicities related to any prior treatments, unless the adverse events are clinically non-significant and/or stable on supportive therapy
• Life expectancy of 12 weeks or longer
• Age ≥ 19 years old
• ECOG performance status of 0, 1
• Adequate hematological function
• Absolute neutrophil count (ANC) ≥ 1.0 x109/L
• Platelets ≥ 75 x 109/L
• Hemoglobin ≥ 10 g/dL
• Adequate renal function
• serum creatinine ≤ 1.5 × upper limit of normal or calculated creatinine clearance ≥ 40 mL/min (using the Cockroft-Gault equation) AND

You may not qualify if:

• Fibrolamellar carcinoma or mixed hepatocellular cholangiocarcinoma
• Prior lenvatinib treatment
• Prior systemic treatment for HCC, except for atezolizumab plus bevacizumab (i.e. lenvatinib must be second-line systemic treatment)
• Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 3 months before randomization.
• The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
• a. Cardiovascular disorders including i. Significant cardiovascular impairment: history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, myocardial infarction or stroke within 6 months of the first dose of study drug, or cardiac arrhythmia requiring medical treatment at Screening.
• ii. Uncontrolled blood pressure (Systolic BP\>150 mmHg or diastolic BP \>90 mmHg) in spite of an optimized regimen of antihypertensive medication.
• iii. Stroke (including TIA), myocardial infarction, or other ischemic event within 6 months iv. Bleeding or thrombotic disorders or subjects at risk for severe hemorrhage. The degree of tumor invasion/infiltration of major blood vessels (e.g. carotid artery) should be considered because of the potential risk of severe hemorrhage associated with tumor shrinkage/necrosis following lenvatinib therapy.
• b. Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation/bleeding: i. Tumors invading the GI tract, active peptic ulcer disease, inflammatory bowel disease, diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis or acute obstruction of the pancreatic duct or common bile duct, or gastric outlet obstruction ii. Abdominal fistula, GI perforation, bowel obstruction, intra-abdominal abscess within 6 months
• Major surgery within 2 months before randomization. Complete healing from major surgery must have occurred 1 month before randomization. Complete healing from minor surgery (eg, simple excision, tooth extraction) must have occurred at least 7 days before registration. Subjects with clinically relevant co d. Cavitating pulmonary lesion(s) or endobronchial disease
• Moderate or severe ascites (Radiologically detected but clinically insignificant ascites is allowed)
• Corrected QT interval calculated by the Fridericia formula (QTcF) \> 500 ms within 21 days of registration
• \* If the QTcF is \> 500 ms in first ECG, a total of 3 ECGs should be performed. If the average of these 3 consecutive results for QTcF is ≤ 500 ms, the subject meets eligibility in this regard.
• Subjects having \> 1+ proteinuria on urine dipstick testing unless a 24-hour urine collection for quantitative assessment indicates that the urine protein is \<1 g/24 hours.
• Previously identified allergy or hypersensitivity to components of the study treatment formulations

Sponsors & Collaborators

• Asan Medical Center: lead
• Eisai Inc.: collaborator
• Chonnam National University Hospital: collaborator
• Seoul National University: collaborator
• Gangneung Asan Hospital: collaborator
• Ulsan University Hospital: collaborator
• Chosun University Hospital: collaborator
• Dong-A University Hospital: collaborator
• Bundang CHA Hospital: collaborator
• Seoul National University Bundang Hospital: collaborator
• Yonsei University: collaborator
• Hanyang University Seoul Hospital: collaborator
• Chungnam National University Hospital: collaborator
• Saint Vincent's Hospital, Korea: collaborator
• Gyeongsang National University Hospital: collaborator
• Ewha Womans University: collaborator
• Chungbuk National University Hospital: collaborator
• Severance Hospital: collaborator
• Gachon University Gil Medical Center: collaborator
• The Catholic University of Korea: collaborator
• Bucheon St. Mary's Hospital: collaborator

Study Sites (1)

Asan Medical Center

Seoul, 05505, South Korea

Location

Related Publications (4)

• Kudo M, Finn RS, Qin S, Han KH, Ikeda K, Piscaglia F, Baron A, Park JW, Han G, Jassem J, Blanc JF, Vogel A, Komov D, Evans TRJ, Lopez C, Dutcus C, Guo M, Saito K, Kraljevic S, Tamai T, Ren M, Cheng AL. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet. 2018 Mar 24;391(10126):1163-1173. doi: 10.1016/S0140-6736(18)30207-1.

  PMID: 29433850 BACKGROUND

• Finn RS, Qin S, Ikeda M, Galle PR, Ducreux M, Kim TY, Kudo M, Breder V, Merle P, Kaseb AO, Li D, Verret W, Xu DZ, Hernandez S, Liu J, Huang C, Mulla S, Wang Y, Lim HY, Zhu AX, Cheng AL; IMbrave150 Investigators. Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma. N Engl J Med. 2020 May 14;382(20):1894-1905. doi: 10.1056/NEJMoa1915745.

  PMID: 32402160 BACKGROUND

• Vogel A, Cervantes A, Chau I, Daniele B, Llovet JM, Meyer T, Nault JC, Neumann U, Ricke J, Sangro B, Schirmacher P, Verslype C, Zech CJ, Arnold D, Martinelli E; ESMO Guidelines Committee. Hepatocellular carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2018 Oct 1;29(Suppl 4):iv238-iv255. doi: 10.1093/annonc/mdy308. No abstract available.

  PMID: 30285213 BACKGROUND

• Kim HD, Sym SJ, Chon HJ, Kim M, Kang JH, Ryoo BY, Lee CK, Hong J, Ryu H, Bae WK, Kim H, Kim H, Kim JW, Kim TY, Yoo C. Multicenter phase II trial of lenvatinib in patients with advanced hepatocellular carcinoma after progression on first-line atezolizumab plus bevacizumab. J Hepatol. 2025 Sep 4:S0168-8278(25)02457-2. doi: 10.1016/j.jhep.2025.08.020. Online ahead of print.

  PMID: 41038766 DERIVED

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

lenvatinib

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

• Changhoon Yoo, MD, PhD

  Asan Medical Center

  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: Associate Professor

Study Record Dates

• First Submitted: November 14, 2023
• First Posted: November 18, 2023
• Study Start: July 20, 2023
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2027
• Last Updated: July 3, 2024

Record last verified: 2024-06

Locations

KR (1)