Toripalimab + Lenvatinib for Liver Cancer

Not currently recruiting at 38 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for advanced liver cancer that cannot be treated with surgery or has worsened after treatment. It compares the effectiveness of Toripalimab, an immunotherapy that helps the immune system fight cancer, combined with Lenvatinib, a targeted therapy drug, to a placebo combined with Lenvatinib. The goal is to determine if this combination works better than the current standard treatment. People with liver cancer unsuitable for surgery and who have not tried systemic treatments before might be a good fit for this study. As a Phase 3 trial, this study represents the final step before FDA approval, offering patients a chance to access potentially groundbreaking treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the combination of Toripalimab and Lenvatinib is generally well-tolerated by patients. Studies have found that this combination has manageable side effects and is effective against liver cancer, with no unexpected safety issues reported.

Previous patients reported common side effects like tiredness and high blood pressure, mostly mild to moderate. More serious side effects occurred less frequently. The combination has been tested for similar conditions, yielding promising results.

This trial is in a late stage, indicating a good understanding of the treatment's safety and patient response. For prospective participants, this is a positive sign. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for liver cancer?

Researchers are excited about this treatment combination for liver cancer because it brings together Toripalimab, an innovative immunotherapy, with Lenvatinib, a targeted therapy already used in treatment. Unlike traditional treatments that may rely solely on chemotherapy, Toripalimab is a PD-1 inhibitor that works by helping the immune system recognize and attack cancer cells more effectively. When combined with Lenvatinib, which blocks the proteins that promote tumor growth, this dual approach could potentially enhance the overall effectiveness of liver cancer treatment, offering new hope to patients. This combination aims to improve patient outcomes by harnessing the body's own immune system alongside targeted cancer growth inhibition.

What evidence suggests that this trial's treatments could be effective for liver cancer?

Research shows that using Toripalimab and Lenvatinib together may help treat advanced liver cancer (HCC). In this trial, participants in the experimental group will receive this combination. Earlier studies found that this combination led to smaller tumors and manageable side effects. Toripalimab helps the immune system find and attack cancer cells, while Lenvatinib targets and blocks proteins that tumors need to grow. Together, they have shown promise in improving outcomes for advanced HCC. These findings suggest that this combination could be a hopeful option for treating liver cancer. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

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 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.

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

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12540137/

Case Report: Efficacy of preoperative conversion therapy with ... The successful experience of this case indicates that lenvatinib, toripalimab combined with HAIC has a good prospect as a conversion therapy for ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0959804922004257

Lenvatinib, toripalimab plus hepatic arterial infusion ... Lenvatinib, toripalimab and FOLFOX-HAIC showed safe and encouraging antitumour activity for advanced HCC with high-risk features.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04523493

NCT04523493 | Phase III Study of Toripalimab（JS001） ... This is a prospective, randomized, placebo-controlled, double-blind, multicenter phase III registration clinical study to observe, compare and evaluate the ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2021.39.15_suppl.4083

A phase II trial of lenvatinib plus toripalimab and hepatic ... Combination treatment with lenvatinib and toripalimab plus HAIC showed promising antitumor activity and manageable toxicity in patients with advanced HCC.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04368078

Study Details | NCT04368078 | Lenvatinib Combined ... The investigators design a phase IIB clinical study to explore the efficacy and safety of Lenvatinib plus Toripalimab in patients with advanced hepatocellular ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9887048/

Safety and feasibility of toripalimab plus lenvatinib with or ... Toripalimab shows antitumor efficacy in cholangiocarcinoma. Radiotherapy (RT) may enhance systemic responses of PD-1 inhibitors and lenvatinib.

7. asco.org asco.org/abstracts-presentations/ABSTRACT332263

A phase II trial of lenvatinib plus toripalimab and hepatic ... A phase II trial of lenvatinib plus toripalimab and hepatic arterial infusion chemotherapy as a first-line treatment for advanced hepatocellular carcinoma ( ...