Lenvatinib Combined Toripalimab in Advanced Hepatocellular Carcinoma

March 27, 2023 updated by: Peking Union Medical College Hospital

Lenvatinib Combined Toripalimab in Advanced Hepatocellular Carcinoma: a Single-center, Single-arm, Non-randomized Clinical Study

The investigators design a phase IIB clinical study to explore the efficacy and safety of Lenvatinib plus Toripalimab in patients with advanced hepatocellular carcinoma and to analyze potential biomarkers of therapeutic response.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This trial is a single-arm, non-randomized and single-center clinical study of targeted therapy combined immunotherapy in patients with hepatocellular carcinoma.

It is estimated that 76 patients who met the study criteria will be enrolled in Peking Union Medical College Hospital(PUMCH) and treated with Lenvatinib and Toripalimab. The investigators will follow up and collect subjects' data monthly to evaluate the efficacy and safety of treatment, including overall survival and time to progression. Multi-omics data analysis will be used to find potential biomarkers of treatment response.

Study Type

Interventional

Enrollment (Anticipated)

76

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Beijing
      • Beijing, Beijing, China, 100730
        • Recruiting
        • Chinese Academy of Medical Sciences & Peking Union Medical College Hospital
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Subjects volunteer to participate in the study and agree to sign the informed consent with good compliance and follow-up.
  • Subjects are 18 years old or older when signing the informed consent and gender is not limited.
  • Imaging (by AASLD or Standard for the diagnosis and treatment of primary liver cancer 2017 in China) or histopathologically or cytologically confirmed advanced Hepatocellular carcinoma.
  • BCLC stage B or C. The disease is not suitable for radical surgery and/or topical treatment, or disease progression occurs after surgery and/or local treatment.
  • Subjects who have received first-line systemic treatment (targeted therapies other than Lenvatinib, chemotherapy, biological immunotherapy, etc.) except Toripalimab and Lenvatinib could be involved.
  • At least one measurable lesion (according to RECIST version 1.1): the measurable lesion has a long diameter ≥ 10 mm or lymphadenpathy has a short diameter ≥ 15 mm in spiral CT scan.
  • The ECOG score is 0-1 within 1 week before enrollment.
  • Liver function assessment: Child-Pugh Grade A (5-6 points).
  • Estimated survival time ≥ 3 months.
  • 10. Subjects with HBV infection: HBV DNA<2000 IU/ml or <10^4 copy/mL, and have received anti-HBV therapy for at least 14 days prior to enrollment in the study, subjects with HCV-RNA(+) must receive antiviral therapy;
  • Hematology and organ function are sufficient based on the following laboratory results within 14 days prior to the treatment of this study:
  • Whole blood cell examination (no blood transfusion within 14 days, no G-CSF use and no drugs use): WBC≥3.0×10^9/L, Hb≥85g/L, ANC≥1.5×10^9/L, PLT≥75×10^9/L.
  • Biochemical examination (no ALB infused within 14 days): ALB≥29 g/L, ALP and ALT and AST<5×ULN, TBIL≤3×ULN, creatinine≤1.5×ULN or CCr >50mL/min (standard Cockcroft-Gault formula): Female: CrCl=((140-age) × body weight (kg) × 0.85) / 72 × Serum creatinine (mg/dL); Male: CrCl=((140- age) × body weight (kg) × 1.00) / 72 × Serum creatinine (mg/dL)
  • Agree to abstain from sex (avoid heterosexual intercourse) or use contraceptive methods with an annual contraceptive failure rate of less than 1% during treatment and for at least 6 months after the last administration.

Exclusion Criteria:

  • Hepatocellular carcinoma patients with any of the following: Suitable for radical surgery; or without an assessment lesion after radical surgery; or liver transplantation history or ready for liver transplantation;
  • ECOG score ≥ 2 points.
  • Previously received Lenvatinib or Toripalimab treatment.
  • History of hepatic encephalopathy.
  • Histopathological result show hepatobiliary carcinoma, sarcomatoid liver cancer, mixed cell carcinoma and layered cell carcinoma.
  • Already known to be allergic or intolerant to recombinant humanized PD-1 monoclonal antibody drugs (or components) or Lenvatinib.
  • Pregnant (positive pregnancy test before taking medicine) or lactating women.
  • Received any topical treatment within 4 weeks prior to the study, including but not limited to surgery, radiotherapy, hepatic artery embolization, TACE, hepatic artery perfusion, radiofrequency ablation, cryoablation or percutaneous ethanol injection.
  • Previous or existing grade 3 (CTCAE5.0 ) and above gastrointestinal fistula or non-gastrointestinal fistula (such as skin).
  • Factors affect Lenvatinib use, such as inability to swallow, chronic diarrhea, intestinal obstruction, or other conditions that significantly affect drug intake and absorption.
  • Ascites with clinical symptoms which requires abdominal puncture or drainage therapy, or Child-Pugh score >2.
  • Surgery performed within 4 weeks or minor surgery (simple resection or biopsy) within 7 days prior to the trial and patients must be evaluated before the first medication.
  • Severe cardiovascular and cerebrovascular diseases, including but not limited to acute myocardial infarction, severe/unstable angina pectoris, cerebrovascular accident or transient ischemic attack, congestive heart failure and arrhythmias within 6 months before enrollment.
  • Hepatic and renal dysfunction evidence: jaundice, ascites, and/or bilirubin ≥ 3× ULN, and/or ≥ 3 grade (CTC-AE 5.0) proteinuria (> 3.5g /24 hours), or renal failure requiring blood dialysis or peritoneal dialysis, and / or urine examination shows urinary protein ≥ ++ or 24 hours urine protein >1.0g.
  • Persistent >2 grade (CTCAE 5.0) infection.
  • Thromboembolism (including stroke and / or transient ischemic attack) within 12 months.
  • Hypertension that cannot be controlled well with antihypertensive drugs (systolic blood pressure> 160mmHg, diastolic blood pressure> 100mmHg).
  • Already known active central nervous system metastasis and/or cancerous meningitis.
  • Active autoimmune disease or autoimmune disease within two years.
  • Known central nervous system metastasis and/or cancerous meningitis.
  • Prepared or previously received an organ or allogeneic bone marrow transplant
  • History of active tuberculosis, such as mycobacterium tuberculosis.
  • Gastrointestinal bleeding history in the past 6 months or tendency to gastrointestinal bleeding, such as esophageal varices, local active ulceration lesions, fecal occult blood ≥ (++) (gastroscopy is required when fecal occult blood is (+)).
  • History of human immunodeficiency virus infection.
  • History of hepatitis B virus or hepatitis C virus infection, and not receive regular treatment.
  • Severe non-healing wounds, ulcers or fractures.
  • With other malignant tumors within 5 years.
  • Previous and current evidence of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-associated pneumonia and severe impairment of lung function.
  • Received a potent CYP3A4 inhibitor treatment within 7 days prior to the study or received a potent CYP3A4 inducer within 12 days prior to the study.
  • With other active malignant tumor except Hepatocellular carcinoma within 5 years or simultaneously.
  • Patients are unsuitable for participation in this research after comprehensive assessment by the researchers.
  • Patients participate in another clinical study at the same time.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Toripalimab plus Lenvatinib

Lenvatinib is a novel angiogenesis inhibitor which targets vascular endothelial growth factor 1-3, fibroblast growth factor receptor 1-4, platelet-derived growth factor receptor β, RET and KIT.

Toripalimab is a recombinant anti-human PD-1 monoclonal antibody.
Drug: Toripalimab plus Lenvatinib

Toripalimab 240mg, every 3 weeks, intravenous infused, day 1, 6 weeks a cycle. Lenvatinib 8mg (weight<60kg) or 12mg (weight≥60kg), once a day, oral at least 38 days of each 6 weeks cycle, day 2.

Number of cycle: until progression or unacceptable toxicity events develop

Other Names:
  • JS001 plus E7080

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate (ORR)
Time Frame: Up to 1 year
Proportion of patients whose tumor volume has reached a predetermined value and can maintain a minimum time limit, including complete response and partial response patients.
Up to 1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Disease Control Rate (DCR)
Time Frame: Up to 1 year
Proportion of patients whose tumor volume control (reduced or enlarged) reaches a predetermined value and can maintain a minimum time limit.
Up to 1 year
Progression-free Survival (PFS)
Time Frame: Up to 1 years
A duration from the date of initial treatment with lenvatinib plus pembrolizumab to disease progression (defined by RECIST 1.1) or death of any cause.
Up to 1 years
3-months and 6-month Progression free survival rate
Time Frame: Up to 6 months
Portion of patients who do not experience disease progression (defined by RECIST 1.1) or death of any cause after treated with toripalimab plus lenvatinib for 3 months and 6 months, respectively.
Up to 6 months
6-months and 1-year mortality rate
Time Frame: Up to 1 years
Portion of patients who die of any cause after treated with toripalimab plus lenvatinib at 6 months and 1 year, respectively.
Up to 1 years
Duration of Response (DOR)
Time Frame: Up to 1 years
Duration from the first time reported partial response or complete response to the first time of disease progression or death.
Up to 1 years
Overall Survival (OS)
Time Frame: Up to 2 years
Duration from the date of initial treatment with lenvatinib plus pembrolizumab to the date of death due to any cause.
Up to 2 years
clinical benefit rate (CBR)
Time Frame: up to 2 years
Proportion of patients achieved complete response and partial response for more than 6 months.
up to 2 years
Adverse events (AE)
Time Frame: up to 2 years
Any adverse events related with treatment drugs and details include adverse events type, frequency and severity.
up to 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Peking Union Medical College Hospital

Collaborators

Shanghai Junshi Bioscience Co., Ltd.

Investigators

  • Principal Investigator: Haitao Zhao, MD, Peking Union Medical College Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 11, 2020

Primary Completion (Anticipated)

April 1, 2024

Study Completion (Anticipated)

April 1, 2025

Study Registration Dates

First Submitted

April 27, 2020

First Submitted That Met QC Criteria

April 27, 2020

First Posted (Actual)

April 29, 2020

Study Record Updates

Last Update Posted (Actual)

March 29, 2023

Last Update Submitted That Met QC Criteria

March 27, 2023

Last Verified

January 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • JS-2295

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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