Casdozokitug + Toripalimab + Bevacizumab for Liver Cancer

Recruiting at 45 trial locations

Overseen By Clinical Operations Team

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Coherus Biosciences, Inc.

Disqualifiers: Prior systemic therapy, Anti-IL-27, Fibrolamellar HCC, Moderate ascites, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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: 12 weeks

72 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for liver cancer that cannot be surgically removed or has spread. It evaluates the safety and effectiveness of a new drug, casdozokitug, in combination with toripalimab (an immunotherapy) and bevacizumab (an anti-angiogenic drug). The study includes different groups testing varying doses to determine the best treatment plan. Suitable participants have liver cancer that cannot be treated with surgery and have not received any previous treatments for their cancer. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to significant advancements in liver cancer treatment.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you have received prior systemic therapy for liver cancer, you may not be eligible to participate.

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

Previous studies have shown that the combination of casdozokitug with toripalimab and bevacizumab is well tolerated. The safety profile aligns with known effects of each drug when used individually, meaning the side effects were expected and similar to previous observations. The trial also demonstrated promising early safety results, with patients managing the treatment combination fairly well. This suggests that the treatment is manageable for many, which is encouraging for potential participants. However, discussing these findings with a doctor is crucial to understand their personal implications. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Casdozokitug combined with Toripalimab and Bevacizumab for liver cancer because this treatment approach targets the cancer in a novel way. Unlike standard treatments that might focus solely on inhibiting blood vessel growth, the combination of Casdozokitug and Toripalimab enhances the immune system's ability to fight the cancer. Casdozokitug, a newer agent, is being tested at both lower and higher doses to determine the optimal balance of efficacy and safety. Meanwhile, Toripalimab is an immune checkpoint inhibitor that helps unleash the body's immune response against cancer cells. This combination aims to offer a more comprehensive attack on liver cancer, potentially leading to better outcomes than current treatments.

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

This trial will explore different combinations of casdozokitug, toripalimab, and bevacizumab to enhance the immune system's ability to fight liver cancer. In Arm A, participants will receive a lower dose of casdozokitug combined with toripalimab and bevacizumab. Arm B will test a higher dose of casdozokitug with the same combination. Arm C will focus on toripalimab and bevacizumab without casdozokitug. Research has shown that casdozokitug can activate immune cells like T and NK cells, which help attack cancer cells. Toripalimab and bevacizumab are already used for other types of cancer, indicating potential effectiveness. Previous studies have demonstrated that these treatments together can create positive responses in liver cancer patients, suggesting further exploration is worthwhile. Overall, this combination aims to strengthen the body's natural defenses against cancer growth. ^{3 4 5 6 7}

Are You a Good Fit for This Trial?

This trial is for adults with advanced or metastatic liver cancer that can't be removed by surgery. Participants must have a confirmed diagnosis and at least one measurable, untreated lesion. They should not be candidates for curative treatments or have progressive disease after such treatments.

Inclusion Criteria

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

I have at least one tumor that can be measured and hasn't been treated.

My condition cannot be cured with surgery or local treatments, or it got worse after such treatments.

Exclusion Criteria

I have moderate to severe fluid buildup in my abdomen.

I have had treatment for liver cancer before.

I have been treated with anti-IL-27 therapy before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive casdozokitug in combination with toripalimab plus bevacizumab to evaluate safety and efficacy

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Bevacizumab
• Casdozokitug
• Toripalimab

Trial Overview

The study tests the safety and effectiveness of a new drug combo: Casdozokitug with Toripalimab and Bevacizumab in liver cancer patients. It aims to find the best dose of Casdozokitug when used with the other two drugs.

How Is the Trial Designed?

Group I: Arm B: Casdozokitug Higher dose + Toripalimab + Bevacizumab Experimental Treatment 3 Interventions

Group II: Arm A: Casdozokitug Lower Dose + Toripalimab + Bevacizumab Experimental Treatment 3 Interventions

Group III: Arm C: Toripalimab + Bevacizumab Active Control 2 Interventions

Who Is Running the Clinical Trial?

Coherus Biosciences, Inc.

Lead Sponsor

Trials

19

Recruited

3,700+

Coherus Oncology, Inc.

Lead Sponsor

Published Research Related to This Trial

In a phase II study involving 31 patients with unresectable hepatocellular carcinoma (HCC), the combination of anlotinib and toripalimab resulted in an objective response rate of 29.0% to 32.3%, indicating promising efficacy as a first-line treatment.

The treatment demonstrated a median progression-free survival of 11.0 months and a median overall survival of 18.2 months, with manageable safety profiles, as the most common severe side effects were hand-foot syndrome, hypertension, and arthralgia, each occurring in about 9.7% of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anlotinib Combined With Toripalimab as First-Line Therapy for Unresectable Hepatocellular Carcinoma: A Prospective, Multicenter, Phase II Study. Zhang, CS., Zeng, ZM., Zhuo, MY., et al.[2023]

Toripalimab, a monoclonal antibody targeting the PD-1 receptor, was well tolerated in a phase I study with 33 heavily pretreated patients, showing no dose-limiting toxicity up to 10 mg/kg every two weeks.

The treatment demonstrated promising efficacy, with an objective response rate of 22.7% in solid tumors and a remarkable 90.9% in lymphoma patients, along with a median duration of response of 21.5 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and clinical efficacy of toripalimab, a PD-1 mAb, in patients with advanced or recurrent malignancies in a phase I study. Yang, J., Dong, L., Yang, S., et al.[2020]

Atezolizumab plus bevacizumab therapy shows promising efficacy for advanced hepatocellular carcinoma (HCC), achieving an objective response rate of 15.6% and a high disease control rate of 93.8% among 34 patients, regardless of liver function or treatment line.

Following the failure of atezolizumab plus bevacizumab therapy, lenvatinib treatment can also be effective, but careful monitoring of liver function is necessary, as indicated by significant reductions in liver function scores in patients receiving lenvatinib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current Role of Atezolizumab Plus Bevacizumab Therapy in the Sequential Treatment of Unresectable Hepatocellular Carcinoma. Komatsu, S., Yano, Y., Fujishima, Y., et al.[2022]

The COI-B regimen, which includes capecitabine, oxaliplatin, irinotecan, and bevacizumab, demonstrated a high pathologic response rate of 63% in patients with potentially resectable colorectal cancer liver metastases, indicating its efficacy as a perioperative treatment strategy.

Dynamic imaging biomarkers, such as early tumor shrinkage (ETS) and lower SUV-2, were found to be significantly associated with pathologic response, suggesting they could be useful for early prediction of treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perioperative Bevacizumab-based Triplet Chemotherapy in Patients With Potentially Resectable Colorectal Cancer Liver Metastases. Pietrantonio, F., Cotsoglou, C., Fucà, G., et al.[2019]

Toripalimab, an immune checkpoint inhibitor, significantly improves progression-free survival and overall survival in advanced esophageal squamous cell carcinoma when combined with chemotherapy, as shown in the JUPITER-06 trial.

However, from a cost-effectiveness perspective in China, adding toripalimab to chemotherapy is not considered cost-effective unless its price is reduced by over 40%, as the incremental cost-effectiveness ratio exceeds the country's willingness-to-pay threshold.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-effectiveness of toripalimab plus chemotherapy for advanced esophageal squamous cell carcinoma. Xu, K., Wu, H., Zhou, C., et al.[2023]

In a study of 40 Taiwanese patients with unresectable hepatocellular carcinoma (HCC), the combination of bevacizumab and atezolizumab showed a response rate of 37.5% and a disease control rate of 85%, indicating significant efficacy as a first-line treatment.

The median overall survival was 24.9 months, and while common adverse events included proteinuria and hypertension, treatment interruptions did not negatively impact progression-free survival or overall survival, suggesting a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab and atezolizumab as first-line therapy for advanced hepatocellular carcinoma: A Taiwanese subgroup analysis on efficacy and safety. Shao, YY., Feng, YH., Yen, CJ., et al.[2022]

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 study of 105 patients with colorectal liver metastases, adding bevacizumab to 5FU/OX chemotherapy significantly reduced tumor viability compared to chemotherapy alone (32.9% vs 45.3%; P = .02).

Patients receiving bevacizumab also experienced lower rates and severity of hepatic sinusoidal dilation, indicating less liver injury, with any grade incidence at 27.4% compared to 53.5% in the 5FU/OX-only group (P < .01).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab improves pathologic response and protects against hepatic injury in patients treated with oxaliplatin-based chemotherapy for colorectal liver metastases. Ribero, D., Wang, H., Donadon, M., et al.[2022]

In a study of 22 patients with unresectable liver cancer, adding intravenous bevacizumab (Bev) to hepatic arterial infusion (HAI) with floxuridine (FUDR) and dexamethasone (Dex) resulted in a partial response in 31.8% of patients and stable disease in 68.2%, with a median survival of 31.1 months.

However, the addition of Bev increased biliary toxicity, with 24% of patients experiencing elevated bilirubin levels, leading to the premature termination of the trial, as there was no significant improvement in progression-free survival compared to HAI alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treating primary liver cancer with hepatic arterial infusion of floxuridine and dexamethasone: does the addition of systemic bevacizumab improve results? Kemeny, NE., Schwartz, L., Gönen, M., et al.[2021]

In a study of 74 patients with colorectal liver metastases, the combination of chemotherapy and bevacizumab showed a high overall response rate of 63.4% and a complete resection rate of 71.6%.

Achieving an optimal pathological response was linked to longer overall survival and trends towards improved progression-free and relapse-free survival, indicating that this treatment approach is both effective and well-tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy Plus Bevacizumab as Neoadjuvant or Conversion Treatment in Patients with Colorectal Liver Metastases. García-Alfonso, P., Cavanagh Podesta, M., Muñoz Martín, A., et al.[2018]

In a study of 191 patients with unresectable hepatocellular carcinoma (HCC), the combination therapy of atezolizumab and bevacizumab showed similar overall survival and progression-free survival rates in older patients (≥65 years) compared to younger patients (<65 years), indicating its efficacy across age groups.

The safety profile of the combination therapy was comparable between older and younger patients, with similar rates of treatment-related adverse events, including severe adverse events, suggesting that older patients can tolerate this treatment as well as younger patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of older age in patients receiving atezolizumab and bevacizumab for hepatocellular carcinoma. Vithayathil, M., D'Alessio, A., Fulgenzi, CAM., et al.[2023]

In a study involving 146 patients with previously treated unresectable hepatocellular carcinoma (HCC), combining local ablation with the PD-1 inhibitor toripalimab significantly improved treatment outcomes, showing a higher objective response rate (33.8% vs. 16.9%) and longer progression-free survival (7.1 months vs. 3.8 months) compared to toripalimab alone.

The combination treatment also resulted in better overall survival (18.4 months vs. 13.2 months) while maintaining an acceptable safety profile, with only a small percentage of patients experiencing severe adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase 1/2 Multicenter Randomized Trial of Local Ablation plus Toripalimab versus Toripalimab Alone for Previously Treated Unresectable Hepatocellular Carcinoma. Zhou, C., Li, Y., Li, J., et al.[2023]

Neoadjuvant treatment with bevacizumab plus chemotherapy (BEV + CT) significantly improved the 5-year disease-free survival (DFS) rate in patients with HER2-negative nonmetastatic breast cancer compared to chemotherapy alone, with a hazard ratio of 0.84.

While BEV + CT also resulted in higher rates of pathological complete response (pCR) in both hormone receptor-positive and negative breast cancer patients, there was no significant difference in the 5-year overall survival (OS) rate between the two treatment groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early and late outcomes of bevacizumab plus chemotherapy versus chemotherapy alone as a neoadjuvant treatment in HER2-negative nonmetastatic breast cancer: a meta-analysis of randomized controlled trials. Wei, J., Luo, Y., Fu, D.[2022]

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