Neoplasms

All Conditions

Digestive System Diseases

Carcinoma

Carcinoma, Hepatocellular

Adenocarcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Liver Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Antineoplastic Agents

All Drugs and Chemicals

Lenvatinib

Protein Kinase Inhibitors

Enzyme Inhibitors

Experimental group:

Toripalimab, 240mg, IV infusion, every 3 weeks (q3w). combined with Lenvatinib 12 mg/day (Body Weight≥60 kg) or 8 mg/day (Body Weight\<60 kg) oral administration, once daily. Continuous infusion, in a cycle of 3 weeks (21 days), until occurrence of termination event specified in the protocol.

Toripalimab combined with Lenvatinib

Control group:

Placebo, one unit, IV infusion, once every 3 weeks, combined with Lenvatinib 12 mg/day (Body Weight≥60 kg) or 8 mg/day (Body Weight\<60 kg) oral administration, once daily. Continuous infusion, in a cycle of 3 weeks (21 days), until occurrence of termination event specified in the protocol.

Placebo combined with Lenvatinib

This is a prospective, randomized, placebo-controlled, double-blind, multicenter phase III registration clinical study to observe, compare and evaluate the efficacy and safety of Toripalimab combined with Lenvatinib versus placebo combined with Lenvatinib as the 1st-line therapy for advanced HCC.

Eligible subjects will be randomized at a ratio of 2:1 to receive Toripalimab combined with Lenvatinib (experimental group) or Placebo combined with Lenvatinib (control group).

Phase III Study of Toripalimab（JS001） Combined With Lenvatinib for Advanced HCC

A Prospective, Randomized, Placebo-controlled, Double-blind, Multicenter Phase III Study to Compare Toripalimab Combined With Lenvatinib Versus Placebo Combined With Lenvatinib as the 1st-line Therapy for Advanced HCC

Tumor biopsy specimen collected before the treatment and tumor specimen collected at progression of tumor will be used for immunohistochemical staining test to determine the expression of PD-L1

Correlation between TMB of tumor tissue and the efficacy

The time from randomization to death for any reason.

Defined as the proportion of subjects with the best overall response of complete response (CR) or partial response (PR).

Defined as the time from the first evaluation of CR or PR to the first evaluation of PD or death for any reason.

Defined as the proportion of subjects with the best overall response (BOR) of CR, PR or SD.

Defined as the time from randomization to objective tumor progression.

The time from randomization to progression of disease or death for any reason, whichever comes first. Progression of disease will be evaluated

The PFS rate on 6 months and 1year in both groups.

The OS rate on 1year and 2years in both groups.

Verbatim descriptions of adverse events will correspond to MedDRA synonymous terms, and AEs will be graded in accordance with NCI-CTCAE version 5.0. All the adverse events during or after the first dose of study drug will be summarized by treatment groups and NCI CTCAE grade. In addition, serious adverse events, adverse events (grade 3 or above) and the adverse events leading to discontinuation or suspension of study drug will be summarized correspondingly. Multiple occurrence of the same event will be counted once in accordance with the highest severity. The proportion of subjects with at least one adverse event will be reported by term of toxicity and treatment groups.

According to the test of blood samples, the pharmacokinetic parameters of Toripalimab, mainly trough concentration, will be analyzed.

Plasma level of anti-Toripalimab injection (JS001) antibody, immunoglobulin and Toripalimab injection (JS001) will be summarized descriptively.

Shanghai Junshi Bioscience Co., Ltd.

Symptoms and General Pathology

Rare Diseases

Cholangiocarcinoma

Death

Bile Duct Cancer

Intrahepatic Cholangiocarcinoma

Antibodies

Gemcitabine

Oxaliplatin

Immunoglobulins

1. Toripalimab: 240 mg, intravenous infusion, Q3W;
2. Lenvatinib: 8mg (body weight \<60kg) or 12mg (body weight ≥60kg), qd;

1. Lenvatinib: 8mg (body weight \<60kg) or 12mg (body weight ≥60kg), qd
2. Gemox chemotherapy D1: Oxaliplatin 85mg / m2, Gemcitabine 1g / m2 D8: Gemcitabine 1g / m2 Three weeks are a course, a total of 6-8 courses

Lenvatinib combined with gemox

Toripalimab combined with lenvatinib

Jian Zhou, MD & PhD

We aim to explore the effects and safety of the two cohorts of toripalimab combined with lenvatinib or gemox combined with lenvatinib as first-line therapy in advanced or unresectable intrahepatic cholangiocarcinoma

For advanced intrahepatic cholangiocarcinoma (ICC) that cannot be surgically removed or accompanied by metastasis, the NCCN guidelines (NCCN guidelines hepatobiliary cancer, 2019) recommend that the current treatment options are limited, mainly recommending gemcitabine combined with platinum-based antitumor drugs (cisplatin, oxaliplatin, etc.) chemotherapy as first-line treatment. Adding targeted drugs can enhance the anti-tumor effect. For those with microsatellite instability, it is recommended to add anti-PD1(programmed cell death protein 1) antibody. Gemox chemotherapy (oxaliplatin + gemcitabine) has been used in the treatment of advanced intrahepatic cholangiocarcinoma, but the efficacy is still not satisfactory. Lenvatinib is a small-molecule multi-kinase inhibitor that is currently approved for first-line treatment of advanced hepatocellular carcinoma. In recent years, the anti-PD1 antibody has shown efficacy in the treatment of primary liver cancer. Lenvatinib combined with anti-PD1 antibody or chemotherapy may have a better effect than single use for advanced ICC. At present, lenvatinib combined with anti-PD1 antibody or lenvatinib combined with Gemox in the first-line treatment of advanced ICC has not been reported.

Arm1: toripalimab combined with lenvatinib， Arm 2: lenvatinib combined with Gemox

Two-cohort Study of Toripalimab(PD1)+Lenvatnib, or Gemox+Lenvatinib in Advanced Intrahepatic Cholangiocarcinoma

A Randomized, Open, Two-cohort Phase 2 Study of Toripalimab(PD1) Combined With Lenvatnib, or Gemox Chemotherapy Combined With Lenvatinib as First-line Therapy in Patients With Advanced or Unresectable Intrahepatic Cholangiocarcinoma

Objective response rate of advanced and unresectable intrahepatic cholangiocarcinoma

From the beginning date of combined therapy to the date of death

From the beginning date of combined therapy to disease progression or death, whichever occurs first.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Phase III Study of Toripalimab（JS001） Combined With Lenvatinib for Advanced HCC	NCT04523493	Advanced Hepato...	Toripalimab com... Placebo combine...	18 Years - 75 Years	Shanghai Junshi Bioscience Co., Ltd.
Two-cohort Study of Toripalimab(PD1)+Lenvatnib, or Gemox+Lenvatinib in Advanced Intrahepatic Cholangiocarcinoma	NCT04361331	Cholangiocarcin...	Lenvatinib comb... Toripalimab com...	18 Years - 75 Years	Shanghai Zhongshan Hospital

Spots Global Cancer Trial Database for toripalimab combined with lenvatinib