Toripalimab + Lenvatinib for Liver Cancer

Recruiting at 35 trial locations

Overseen By Kai Cheng

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Shanghai Junshi Bioscience Co., Ltd.

Must be taking: Entecavir, Tenofovir

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Other cancers, Autoimmune diseases, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 3 years

530 Participants Needed

Trial Summary

What is the purpose of this trial?

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).

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on anti-HBV therapy, you are required to continue it throughout the study. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug combination of Toripalimab and Lenvatinib for liver cancer?

Research shows that combining Toripalimab with Lenvatinib and chemotherapy can improve survival and disease control in advanced liver cancer compared to using Lenvatinib alone. This combination has shown promising results in terms of longer progression-free survival and overall survival, with a higher rate of disease control and response. ^{1 2 3 4 5}

Is the combination of Toripalimab and Lenvatinib safe for liver cancer treatment?

Studies show that both Toripalimab and Lenvatinib, whether used alone or in combination, have acceptable safety profiles for treating advanced liver cancer, with no treatment-related deaths reported. ^{1 2 3 6 7}

How is the drug combination of Toripalimab and Lenvatinib unique for liver cancer treatment?

The combination of Toripalimab and Lenvatinib is unique because it combines an immune checkpoint inhibitor (Toripalimab) with a targeted therapy (Lenvatinib), potentially enhancing the body's immune response against liver cancer while also inhibiting tumor growth. This dual approach may offer improved outcomes compared to using Lenvatinib alone, as suggested by studies showing longer progression-free survival and overall survival in patients with advanced liver cancer. ^{1 2 3 8 9}

Eligibility Criteria

Adults aged 18-75 with advanced liver cancer (HCC), who haven't had systemic treatments for HCC, can join this trial. They should be in relatively good health (ECOG score 0-1) and have a life expectancy of at least 12 weeks. Women must test negative for pregnancy and use birth control, as must men if their partners can bear children.

Inclusion Criteria

I haven't had a blood transfusion or taken blood cell-boosting drugs in the last 14 days.

I have not used any drug treatments for my liver cancer.

I am not pregnant, can take a pregnancy test, and will use birth control during and after the trial.

Exclusion Criteria

Other participants who are unsuitable for inclusion as judged by the investigator.

I have not received a live vaccine in the last 30 days.

I cannot swallow pills or have a condition that affects how my body absorbs food or medicine.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Toripalimab combined with Lenvatinib or Placebo combined with Lenvatinib as the 1st-line therapy for advanced HCC

Up to 3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 90 days after the last investigational product administration

Treatment Details

Interventions

• Lenvatinib
• Toripalimab

Trial Overview The study is testing the effectiveness of Toripalimab combined with Lenvatinib versus a placebo combined with Lenvatinib in treating advanced liver cancer. Participants are randomly assigned to either the experimental group or control group in a ratio of 2:1.

Participant Groups

Group I: Experimental group Experimental Treatment 1 Intervention

Toripalimab combined with Lenvatinib

Group II: Control group Placebo Group 1 Intervention

Placebo combined with Lenvatinib

Lenvatinib is already approved in United States, European Union for the following indications:

Approved in United States as Lenvima for:

• Differentiated Thyroid Cancer
• Renal Cell Carcinoma
• Hepatocellular Carcinoma
• Endometrial Cancer

Approved in European Union as Lenvima for:

• Thyroid Cancer
• Renal Cell Carcinoma
• Hepatocellular Carcinoma
• Endometrial Cancer

Approved in European Union as Kisplyx for:

• Renal Cell Carcinoma

Who Is Running the Clinical Trial?

Shanghai Junshi Bioscience Co., Ltd.

Lead Sponsor

Trials

121

Recruited

28,800+

Findings from Research

In a phase II trial involving 30 patients with advanced hepatocellular carcinoma (HCC), the combination of FOLFOX chemotherapy with lenvatinib and toripalimab resulted in a promising 6-month progression-free survival (PFS) rate of 66.7% and a median overall survival (OS) of 14.63 months.

The study identified potential biomarkers for treatment response, indicating that patients with higher levels of tumor-infiltrating immune cells benefited more from the therapy, while specific hepatocyte subtypes (AKR1C2+ and CFHR4+) were linked to reduced clinical benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenvatinib, toripalimab plus FOLFOX chemotherapy in hepatocellular carcinoma patients with extrahepatic metastasis: A biomolecular exploratory, phase II trial (LTSC). He, M., Huang, Y., Du, Z., et al.[2023]

In a phase Ib study involving 104 patients with unresectable hepatocellular carcinoma (uHCC), the combination of lenvatinib and pembrolizumab demonstrated significant antitumor activity, with an objective response rate of 46% according to modified RECIST criteria.

The treatment was well-tolerated, with manageable toxicities and no new safety signals identified, indicating that this combination could be a viable option for patients with uHCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase Ib Study of Lenvatinib Plus Pembrolizumab in Patients With Unresectable Hepatocellular Carcinoma. Finn, RS., Ikeda, M., Zhu, AX., et al.[2022]

In a study of 71 patients with unresectable hepatocellular carcinoma (uHCC), the combination of lenvatinib and pembrolizumab demonstrated a high disease control rate of 84.1% for first-line treatment, indicating its efficacy in managing this condition.

The treatment did not adversely affect liver function, as measured by the Albumin-Bilirubin (ALBI) score, and factors such as prior nivolumab failure and Child-Pugh class B were associated with poorer progression-free and overall survival, highlighting the need for further investigation in these subgroups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenvatinib plus pembrolizumab for systemic therapy-naïve and -experienced unresectable hepatocellular carcinoma. Wu, CJ., Lee, PC., Hung, YW., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Lenvatinib, toripalimab plus hepatic arterial infusion chemotherapy in patients with high-risk advanced hepatocellular carcinoma: A biomolecular exploratory, phase II trial. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Toripalimab Combined With Hepatic Arterial Infusion Chemotherapy Versus Lenvatinib for Advanced Hepatocellular Carcinoma. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Lenvatinib, toripalimab plus FOLFOX chemotherapy in hepatocellular carcinoma patients with extrahepatic metastasis: A biomolecular exploratory, phase II trial (LTSC). [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

The efficacy and safety of lenvatinib plus transarterial chemoembolization in combination with PD-1 antibody in treatment of unresectable recurrent hepatocellular carcinoma: a case series report. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Phase Ib Study of Lenvatinib Plus Pembrolizumab in Patients With Unresectable Hepatocellular Carcinoma. [2022]

6. Germany pubmed.ncbi.nlm.nih.gov

Lenvatinib plus pembrolizumab for systemic therapy-naïve and -experienced unresectable hepatocellular carcinoma. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

A Retrospective Study of Lenvatinib Monotherapy or Combined With Programmed Cell Death Protein 1 Antibody in the Treatment of Patients With Hepatocellular Carcinoma or Intrahepatic Cholangiocarcinoma in China. [2022]

8. England pubmed.ncbi.nlm.nih.gov

High PD-L1 level of advanced hepatic lymphoepithelioma-like carcinoma response favorably to lenvatinib plus toripalimab. [2022]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Safety and feasibility of toripalimab plus lenvatinib with or without radiotherapy in advanced BTC. [2023]