Nofazinlimab + Lenvatinib for Liver Cancer

Recruiting at 77 trial locations

Overseen By Hua Hu, Master

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: CStone Pharmaceuticals

Must be taking: Antivirals

Must not be taking: Corticosteroids, Immunosuppressants

Disqualifiers: HIV/AIDS, Diabetes, Hypertension, 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

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

534 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a multi-center, double-blind, randomized, phase III study to investigate the efficacy and safety of Nofazinlimab (CS1003) in combination with lenvatinib and placebo in combination with lenvatinib in the treatment of subjects with no prior systemic treatment and with unresectable advanced hepatocellular carcinoma (HCC). Subjects cannot be eligible for locoregional therapy. In this study, Nofazinlimab (CS1003) (or placebo) and lenvatinib are both considered as the study treatment while Nofazinlimab (CS1003) (or placebo) is the investigational product of and lenvatinib is selected as the basic treatment for HCC.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot use systemic corticosteroids (more than 10 mg/day prednisone or equivalent) or other immunosuppressive medications within 14 days before starting the study treatment.

What data supports the effectiveness of the drug Nofazinlimab + Lenvatinib for liver cancer?

Research shows that combining lenvatinib with anti-PD-1 antibodies, like nofazinlimab, has shown strong anti-tumor effects in advanced liver cancer, particularly in patients with hepatitis B. This suggests that the combination could be effective for treating liver cancer. ^{1 2 3 4 5}

Is the combination of Nofazinlimab and Lenvatinib safe for humans?

Lenvatinib has been shown to be generally safe in patients with liver cancer, even when used after other treatments have failed. It was well-tolerated when combined with immune checkpoint inhibitors, which are similar to Nofazinlimab. ^{6 7 8 9 10}

What makes the drug Nofazinlimab + Lenvatinib unique for liver cancer?

Nofazinlimab combined with Lenvatinib is unique because it pairs a PD-1 blockade (a type of immune therapy that helps the immune system attack cancer cells) with Lenvatinib, a drug that targets multiple pathways involved in tumor growth. This combination aims to enhance the effectiveness of treatment for liver cancer by using both immune system activation and direct tumor growth inhibition. ^{9 11 12 13 14}

Eligibility Criteria

Adults with advanced hepatocellular carcinoma (HCC) who haven't had systemic treatment and can't have surgery or locoregional therapy. They should be in relatively good health, not pregnant, agree to use contraception, and have no history of certain cancers or serious diseases that could affect the trial's outcome.

Inclusion Criteria

I am at least 18 years old (20 if I'm in Taiwan).

My liver cancer cannot be removed by surgery and is in an advanced stage.

I am not pregnant and agree to use birth control during and 6 months after the study.

Exclusion Criteria

I cannot take pills because my body doesn't absorb nutrients well or for another reason.

I have been diagnosed with HIV/AIDS.

I had surgery or local therapy for symptom relief within the last 4 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Nofazinlimab (CS1003) or placebo in combination with lenvatinib as first-line therapy for advanced hepatocellular carcinoma

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Treatment Details

Interventions

• Nofazinlimab (CS1003)

Trial Overview The study is testing Nofazinlimab combined with Lenvatinib versus a placebo combined with Lenvatinib in treating HCC. Participants are randomly assigned to either group in this double-blind phase III trial to compare effectiveness and safety.

Participant Groups

Group I: Nofazinlimab (CS1003) Experimental Treatment 1 Intervention

Group II: Nofazinlimab (CS1003) placebo Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

CStone Pharmaceuticals

Lead Sponsor

Trials

28

Recruited

4,100+

Findings from Research

In a study of 210 patients with advanced or unresectable hepatocellular carcinoma (HCC), the combination of lenvatinib and anti-PD-1 antibodies showed an objective response rate of 28.1% and a disease control rate of 75.2%, indicating significant anti-tumor efficacy in a real-world setting.

Patients with better liver function (Child-Pugh class A) experienced longer median overall survival (18.8 months) compared to those with poorer liver function (Child-Pugh class B, 5.9 months), highlighting the importance of liver function in treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and safety of lenvatinib plus anti-programmed death-1 antibodies in patients with hepatocellular carcinoma: A real-world cohort study. Xu, MH., Huang, C., Li, ML., et al.[2023]

In a study of 70 patients with unresectable hepatocellular carcinoma (u-HCC) infected with hepatitis B virus (HBV), combining lenvatinib with at least 3 cycles of anti-PD-1 therapy significantly improved overall survival (21.4 months) and progression-free survival (8.0 months) compared to lenvatinib alone (14 months and 6.3 months, respectively).

Patients with portal vein trunk invasion or extrahepatic spread, particularly those with Child-Pugh class B liver function, experienced the greatest benefit from the combination therapy, showing a 38% increase in 12-month survival rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Population Sensitive to Lenvatinib Plus Anti-PD-1 for Unresectable Hepatocellular Carcinoma Infected with Hepatitis B Virus. Chang, X., Yu, S., Pang, J., et al.[2023]

In a study involving 59 patients with advanced hepatocellular carcinoma, the combination of cadonilimab and lenvatinib showed an objective response rate of approximately 35.5% to 35.7%, with a median duration of response around 13.6 months, indicating promising efficacy as a first-line treatment.

While the treatment was effective, it also had a significant safety profile, with 66.1% of patients experiencing grade ≥ 3 treatment-related adverse events, including common issues like decreased platelet count and hypertension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and safety of cadonilimab combined with lenvatinib for first-line treatment of advanced hepatocellular carcinoma (COMPASSION-08): a phase Ib/II single-arm clinical trial. Qiao, Q., Han, C., Ye, S., et al.[2023]

In a study of 118 patients with unresectable hepatocellular carcinoma (HCC), triple therapy combining lenvatinib, a PD-1 inhibitor, and transarterial chemoembolization (TACE) significantly improved overall survival (29.0 months vs. 17.8 months) and progression-free survival (16.2 months vs. 10.2 months) compared to dual therapy with lenvatinib and PD-1 inhibitor.

The triple therapy also resulted in higher objective response rates (76.7% vs. 44.9%) and disease control rates (96.7% vs. 75.9%) without increasing the incidence or severity of adverse events, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of lenvatinib plus PD-1 inhibitor with or without transarterial chemoembolization in unresectable hepatocellular carcinoma. Xin, Y., Zhang, X., Liu, N., et al.[2023]

In a study of 648 matched patients with hepatocellular carcinoma, both atezolizumab plus bevacizumab (Atez/Bev) and lenvatinib (LEN) led to a significant worsening of liver function, as measured by the ALBI score, over 12 weeks, but there was no significant difference in deterioration rates between the two treatments.

Subgroup analyses indicated that LEN-treated patients with advanced BCLC stage or those receiving the full dose experienced a greater decline in liver function, suggesting that caution is needed when using LEN in these populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparing the impact of atezolizumab plus bevacizumab and lenvatinib on the liver function in hepatocellular carcinoma patients: A mixed-effects regression model approach. Hatanaka, T., Kakizaki, S., Hiraoka, A., et al.[2023]

Lenvatinib effectively inhibits the growth of liver cancer cells in vitro and in vivo, with its efficacy varying based on the expression levels of specific receptors (FGFR1-4, RET) in the cancer cells.

In animal models, lenvatinib reduced tumor growth by significantly decreasing blood vessel formation (angiogenesis) and increasing tumor necrosis, although it did not induce apoptosis in the cancer cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antiproliferative Effect of Lenvatinib on Human Liver Cancer Cell Lines In Vitro and In Vivo. Ogasawara, S., Mihara, Y., Kondo, R., et al.[2020]

In a phase 2 study involving 46 patients with advanced hepatocellular carcinoma, lenvatinib demonstrated significant clinical activity with a median time to progression of 7.4 months and a median overall survival of 18.7 months.

The treatment was associated with manageable side effects, although 74% of patients required dose reductions due to adverse events, particularly in those with lower body weight, suggesting that body weight should be considered for dose adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2 study of lenvatinib in patients with advanced hepatocellular carcinoma. Ikeda, K., Kudo, M., Kawazoe, S., et al.[2018]

References

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

A first-in-human phase 1 study of nofazinlimab, an anti-PD-1 antibody, in advanced solid tumors and in combination with regorafenib in metastatic colorectal cancer. [2023]

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

Effectiveness and safety of lenvatinib plus anti-programmed death-1 antibodies in patients with hepatocellular carcinoma: A real-world cohort study. [2023]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Population Sensitive to Lenvatinib Plus Anti-PD-1 for Unresectable Hepatocellular Carcinoma Infected with Hepatitis B Virus. [2023]

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

The efficacy and safety of cadonilimab combined with lenvatinib for first-line treatment of advanced hepatocellular carcinoma (COMPASSION-08): a phase Ib/II single-arm clinical trial. [2023]

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

Efficacy and safety of lenvatinib plus PD-1 inhibitor with or without transarterial chemoembolization in unresectable hepatocellular carcinoma. [2023]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Exploratory Analysis of Lenvatinib Therapy in Patients with Unresectable Hepatocellular Carcinoma Who Have Failed Prior PD-1/PD-L1 Checkpoint Blockade. [2023]

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

Postprogression treatment of lenvatinib plus PD-1 inhibitor in advanced hepatocellular carcinoma refractory to hepatic arterial infusion chemotherapy. [2023]

8. Greece pubmed.ncbi.nlm.nih.gov

Leaky Gut and Severe Adverse Events in Advanced Hepatocellular Carcinoma Treated With Lenvatinib. [2022]

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

Lenvatinib Plus Immune Checkpoint Inhibitors Improve Survival in Advanced Hepatocellular Carcinoma: A Retrospective Study. [2022]

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

Comparing the impact of atezolizumab plus bevacizumab and lenvatinib on the liver function in hepatocellular carcinoma patients: A mixed-effects regression model approach. [2023]

11. Greece pubmed.ncbi.nlm.nih.gov

Antiproliferative Effect of Lenvatinib on Human Liver Cancer Cell Lines In Vitro and In Vivo. [2020]

12. New Zealand pubmed.ncbi.nlm.nih.gov

Feasibility and Tolerability of Lenvatinib, Plus PD-1 Blockades for Patients with Unresectable Hepatocellular Carcinoma: A Retrospective Exploratory Study. [2022]

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

Conversion therapy for unresectable hepatocellular carcinoma after lenvatinib: Three case reports. [2022]

14. Japan pubmed.ncbi.nlm.nih.gov

Phase 2 study of lenvatinib in patients with advanced hepatocellular carcinoma. [2018]