Lenvatinib Combined Toripalimab in Advanced Hepatocellular Carcinoma

• Status: Recruiting
• Trial end date: 2023-04-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Peking Union Medical College Hospital
• Collaborators: Shanghai Junshi Bioscience Co., Ltd.; Shanghai Junshi Biosciences Co., LTD
• Treatments: Lenvatinib

Criteria

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.