Nofazinlimab + Lenvatinib for Liver Cancer

Not currently recruiting at 86 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of a new drug combination for individuals with advanced liver cancer that cannot be treated with surgery or local therapies. It compares the effects of the experimental drug Nofazinlimab (CS1003) combined with lenvatinib against lenvatinib with a placebo. The aim is to determine if adding Nofazinlimab improves patient outcomes. Individuals who have not received systemic treatment for their liver cancer and have at least one measurable tumor may be suitable candidates for this study. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to potentially groundbreaking treatment advancements.

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.

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

Research has shown that Nofazinlimab, when combined with lenvatinib, generally has a manageable safety profile. In a study involving Chinese patients with advanced liver cancer, this combination was mostly well-tolerated, with side effects typically ranging from mild to moderate. Another study tested Nofazinlimab with a different drug for another type of cancer and also found the safety to be manageable.

Lenvatinib, included in this trial, has FDA approval for treating liver cancer, indicating its well-established safety.

This trial is in a later phase, meaning more is known about the treatment's safety. However, discussing this with a doctor is important to understand its implications. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for liver cancer?

Researchers are excited about Nofazinlimab for liver cancer because it offers a fresh approach to treatment. Unlike traditional therapies that often focus on stopping cancer cell growth, Nofazinlimab is an immunotherapy drug designed to help the body's immune system recognize and attack cancer cells. It targets the PD-1 pathway, which can sometimes allow cancer cells to hide from the immune system. By blocking this pathway, Nofazinlimab may enhance the body's natural defenses, potentially leading to better outcomes. Plus, when combined with Lenvatinib, a standard treatment that inhibits tumor blood vessel growth, this combination could prove more effective than existing options alone.

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

This trial will evaluate the effectiveness of nofazinlimab, with some participants receiving nofazinlimab alone and others receiving a placebo. Studies have shown that nofazinlimab, when combined with lenvatinib, offers promising results as a first treatment option for advanced liver cancer, particularly in cases where surgery isn't possible. Research indicates that this combination can lead to significant improvements, including tumor shrinkage. Nofazinlimab is an anti-PD-1 antibody that helps the immune system better recognize and attack cancer cells. Additionally, this combination is generally safe, with manageable side effects. These findings suggest that nofazinlimab, along with lenvatinib, could be an effective option for those with advanced liver cancer. ^{1 5 6 7 8}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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 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 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]

Citations

1. cstonepharma.com cstonepharma.com/en/html/news/3625.html

CStone Announces Publication of First-in-Human Study ... The research data show that nofazinlimab monotherapy demonstrates good safety and tolerability, with no observed dose-limiting toxicities.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04194775

NCT04194775 | A Study of Nofazinlimab (CS1003) in ... This is a multi-center, double-blind, randomized, phase III study to investigate the efficacy and safety of Nofazinlimab (CS1003) in combination with ...

3. clinicaltrials.eu clinicaltrials.eu/trial/study-on-the-effectiveness-and-safety-of-nofazinlimab-and-lenvatinib-for-patients-with-advanced-liver-cancer/

Study on the Effectiveness and Safety of Nofazinlimab ... Nofazinlimab · Lenvatinib. CS1003 is a medication being studied for its potential to help treat advanced liver cancer, specifically hepatocellular carcinoma.

4. firstwordpharma.com firstwordpharma.com/story/5587899

CStone presents updated results of anti-PD-1 antibody ... Nofazinlimab in combination with lenvatinib as first-line treatment for unresectable hepatocellular carcinoma demonstrated an objective ...

5. acsjournals.onlinelibrary.wiley.com acsjournals.onlinelibrary.wiley.com/doi/full/10.1002/cncr.35226

Dual CTLA‐4 and PD‐1 checkpoint blockade using CS1002 ... Treatment-related adverse events (TRAEs) were reported in 30.8%, 83.3%, and 75.0% of patients in parts 1, 2, and 3, respectively. Grade ≥3 TRAEs ...

6. cstonepharma.com cstonepharma.com/uploads/2023/06/168800787342898.pdf

A Phase 1b study of the PD-1 antagonist CS1003 ... Herein, we present the efficacy and safety data of 1L treatment of CS1003 + LEN in Chinese uHCC pts. In this open-label Phase 1b study, Chinese pts with 1L ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10646086/

A first-in-human phase 1 study of nofazinlimab, an anti-PD-1 ... Regorafenib plus nofazinlimab had a manageable safety profile but was not associated with any response in mCRC. Clinical trial registr ation.

8. researchgate.net researchgate.net/publication/361125195_Updated_efficacy_and_safety_results_from_a_phase_1b_study_of_the_PD-1_antagonist_CS1003_combined_with_lenvatinib_LEN_as_first-line_1L_treatment_in_Chinese_patients_pts_with_unresectable_hepatocellular

Updated efficacy and safety results from a phase 1b study ... In addition, the combination of nofazinlimab and an anti-CTLA-4 antibody was explored in one phase 1a/1b study (NCT03523819); this combination ...