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

NCT04523493 | Active Not Recruiting Phase 3 FDA Drug

• 1 other identifier: JS001-027-III-HCC
• Study Type: interventional
• Target: 530
• Locations: 5 countries
• Sites: 22

Brief Summary

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).

Conditions

Advanced Hepatocellular Carcinoma (HCC)

Outcome Measures

Primary Outcomes (1)

• Overall survival (OS)

  The time from randomization to death for any reason.

  Up to 3 years

Secondary Outcomes (10)

• ORR

  Up to 3 years

• Duration of Response (DOR)

  Up to 3 years

• DCR

  Up to 3 years

• TTP

  Up to 3 years

• Progression-free survival (PFS)

  Up to 3 years

Other Outcomes (2)

• Assessment of the correlation between tumor cell PD-L1 expression level/ percentage and efficacy

  Up to 3 years

• Tumor mutation burden (TMB)

  Up to 3 years

Study Arms (2)

Experimental group

EXPERIMENTAL

Toripalimab combined with Lenvatinib

Combination Product: Toripalimab combined with Lenvatinib

Control group

PLACEBO COMPARATOR

Placebo combined with Lenvatinib

Combination Product: Placebo combined with Lenvatinib

Interventions

Toripalimab combined with Lenvatinib COMBINATION_PRODUCT

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.

Experimental group

Placebo combined with Lenvatinib COMBINATION_PRODUCT

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.

Control group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age of 18-75 full years (inclusive), male or female.
• Histopathologically or cytologically confirmed HCC or participants with liver cirrhosis meet the clinical diagnostic criteria for HCC of the American Association for the Study of Liver Diseases (AASLD).
• Stage B (intermediate stage) or C (advanced stage) HCC determined in accordance with Barcelona Clinic Liver Cancer staging system (BCLC stage), be unsuitable for surgery and/or local therapy, or have progression of disease after surgery and/or local therapy.
• No previous use of any systemic therapy for HCC (mainly including systemic chemotherapy, antiangiogenic drugs or other molecular targeted therapy, immunotherapy containing CTLA-4, PD 1/PD-L1 monoclonal antibody).
• Having ≥ 1 measurable lesion in accordance with RECIST v1.1. Requirement: the selected target lesion has not been treated locally before, or is located in the area of previous local therapy and subsequently determined as PD through radiological examination and in accordance with RECIST v1.1.
• Child-Pugh class A or ≤7 class B, with no history of hepatic encephalopathy.
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score 0-1.
• Expected survival ≥12 weeks.
• Main organ function meets the following requirements: no blood transfusion within 14 days prior to screening, no use of hematopoietic stimulating factor (including G-CSF, GM-CSF, EPO and TPO etc.) or human albumin preparation.
• In case of HBsAg (+) and/or HBcAb (+), HBV DNA is required to be \< 1000 IU/mL (if the lowest detectable value at the local center is higher than 1000IU/mL, enrollment can be determined based on the specific condition after discussed with sponsor), and it is required to continue original anti-HBV therapy in the full course, or start to use Entecavir or tenofovir in the full course after screening during the study.
• Female patients at childbearing age must receive serum pregnancy test within 7 days before randomization, have negative result, and are willing to use reliable and effective contraceptive methods during the trial and within 5 months after last administration. Male patients whose partners are women of childbearing potential must agree to use reliable and effective contraceptive methods during the trial and within 5 months after last administration.
• Being voluntary to participate in the study, sufficiently informed consent and sign the written informed consent form, with good compliance.

You may not qualify if:

• Known cholangiocellular carcinoma (ICC) or mixed hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma and hepatic fibrolamellar carcinoma.
• Malignant tumor except HCC within 5 years: however, localized tumor cured in the study is excluded,including cervical carcinoma in situ, skin basal cell carcinoma and carcinoma in situ of prostate.
• Hepatic surgery and/or local therapy or treatment with investigational product for HCC within 4 weeks prior to randomization; palliative radiation therapy for bone metastatic lesion within 2 weeks prior to randomization; use of Chinese medicine preparations with anti-liver cancer effect within two weeks prior to randomization. Toxicity induced by previous therapy (except alopecia) not recovered to ≤ grade 1 (NCI-CTCAE v5.0).
• Prior use of other anti-PD-1 antibody or other immunotherapy targeting PD-1/PD-L1.
• Uncontrolled pericardial effusion, uncontrolled pleural effusion or clinically obvious moderate or severe peritoneal effusion at screening, defined as reaching the following criteria: having clinical symptoms and pleural and peritoneal effusion detected in physical examination at screening; or puncture for drainage required for pleural and peritoneal effusion and/or intracavitary administration during screening.
• History of gastrointestinal hemorrhage within 6 months prior to randomization or clear tendency of gastrointestinal hemorrhage (including severe esophageal-gastric varices with hemorrhagic risk, locally active peptic ulcer, persistent fecal occult blood (+)).
• Having ≥ grade 3 (NCI-CTCAE v5.0) gastrointestinal or non-gastrointestinal fistula at present.
• Cancer thrombus invasion in the main trunk of portal vein (Vp4) (more than 1/2 of the lumen), inferior vena cava cancer thrombus or cardiac involvement in accordance with CT/MRI.
• Serious cardiovascular and cerebrovascular diseases:
• Other obvious hemorrhagic tendency or evidence on important coagulation disorder:
• Medium to large surgical treatment within 4 weeks prior to randomization, not including diagnostic biopsy.
• Serious, uncured wound, active ulcer or untreated bone fracture.
• Vaccination of live vaccine within 30 days prior to randomization.
• Presence of immunodeficiency or receiving long-term systemic steroid therapy within 7 days prior to randomization (daily dose \>10mg Prednisone or other equivalent glucocorticoid), or other immunosuppressive therapy.
• Active autoimmune diseases requiring systemic treatment (i.e., immunomodulatory drug, corticosteroid or immunosuppressant) in the past two years; however, replacement therapy (e.g., thyroxine, insulin or physiological corticosteroid replacement therapy for renal or pituitary insufficiency) will not be considered as systemic therapy and is allowed to be used.

Sponsors & Collaborators

• Shanghai Junshi Bioscience Co., Ltd.: lead

Study Sites (22)

Qinhuai Medical Area, General Hospital of PLA Eastern Theater Command

Nanjing, Jiangsu, 21000, China

Location

Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico,Oncologia Medica

Milan, 20122, Italy

Location

IRCCS Fondazione Giovanni Pascale, Istituto Nazionale Dei Tumori

Naples, 80131, Italy

Location

Azienda Ospedaliero Universitaria Pisana

Pisa, 56126, Italy

Location

A.O.U. Citta della Salute e della Scienza di Torino

Tortona, Italy

Location

AOUI Verona - Policlinico "G.B. Rossi" di Borgo Roma

Verona, 37134, Italy

Location

Copernicus Podmiot Leczniczy sp. z o.o., Wojewodzkie Centrum Onkologii, Oddzial Onkologii Klinicznej/Chemioterapii

Gdansk, 80-219, Poland

Location

Szpital Wojewódzki im. Mikołaja Kopernika w Koszalinie, Oddzial Dzienny Chemioterapii

Koszalin, 75-581, Poland

Location

PRATIA MCM Kraków, ul. Pana Tadeusza 2,

Krakow, 30-727, Poland

Location

ID Clinic

Mysłowice, 41-400, Poland

Location

Wielkopolskie Centrum Onkologii, Oddział Onkologii Klinicznej i Immunoonkologii z Pododdziałem Dziennym i Izbą Przyjęć

Poznan, 61-866, Poland

Location

Centrum Medyczne Pratia Poznań

Skórzewo, 60-185, Poland

Location

Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie - Państwowy Instytut Badawczy, Klinika Onkologii i Radioterapii

Warsaw, 02-034, Poland

Location

National Cancer Centre Singapore

Singapore, 168583, Singapore

Location

Communal Non-commercial Enterprise City Clinical Hospital #4 of Dnipro City Council, Department of Chemotherapy

Dnipro, 49102, Ukraine

Location

Communal Non-profit Enterprise "Regional Center of Oncology", Department of Abdominal Organs Oncosurgery

Kharkiv, 61070, Ukraine

Location

Communal Non-Profit Institution of Kharkiv Regional Council Regional Clinical Specialized Dispensary of Radiation Protection of Population

Kharkiv, 61166, Ukraine

Location

State Inst. O.O.Shalimov Nat. scientific certer of Surgery and Transplantology of Nat. Academy of Med.Sciences of Ukraine, Dep.of Oncology

Kyiv, 03126, Ukraine

Location

Communal Enterprise Volyn Regional Clinical Hospital of Volyn Regional Council

Lutsk, 43018, Ukraine

Location

Communal Non-commercial Enterprise Odesa Regional Clinical Hospital of Odesa Regional Council, Department of General Surgery

Odesa, 65025, Ukraine

Location

Communal Non-commercial Enterprise of Sumy Regional Council, Sumy Regional Clinical Oncological Dispensar

Sumy, 40022, Ukraine

Location

Communal Non-commercial Enterprise Zaporizhzhia Regional Antitumor Center of Zaporizhzhia Regional Council

Zaporizhzhia, 69040, Ukraine

Location

MeSH Terms

Interventions

lenvatinib

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 9, 2020
• First Posted: August 21, 2020
• Study Start: June 29, 2020
• Primary Completion: December 31, 2025
• Study Completion (Estimated): September 1, 2026
• Last Updated: December 9, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

IT (5); CN (1); PL (7); SG (1); UA (8)