Casdozokitug + Toripalimab + Bevacizumab for Liver Cancer

Recruiting in Palo Alto (17 mi)

+1 other location

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Coherus Biosciences, Inc.

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

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

The main goals of this study are to evaluate the safety and efficacy of casdozokitug in combination with toripalimab plus bevacizumab and to define a recommended dose for casdozokitug in combination with toripalimab plus bevacizumab.

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.

What data supports the effectiveness of the drug Bevacizumab for liver cancer?

Research shows that Bevacizumab, when added to chemotherapy, improves the response in patients with liver metastases from colorectal cancer, suggesting it might help in liver cancer treatment by enhancing the effects of other drugs. ^{1 2 3 4 5}

Is the combination of Casdozokitug, Toripalimab, and Bevacizumab safe for humans?

Toripalimab has been studied for safety in various cancers, including liver cancer, and is generally considered safe, though it may cause side effects like fatigue and skin reactions. Bevacizumab is also widely used and generally safe, but it can cause high blood pressure and bleeding. There is no specific safety data available for Casdozokitug in the provided research. ^{6 7 8 9 10}

What makes the drug combination of Casdozokitug, Toripalimab, and Bevacizumab unique for liver cancer?

This drug combination is unique because it includes Casdozokitug, which is not mentioned in standard treatments for liver cancer, and combines it with Toripalimab, an immune checkpoint inhibitor, and Bevacizumab, a drug that inhibits blood vessel growth in tumors. This combination may offer a novel approach by targeting the cancer through multiple mechanisms. ^{6 10 11 12 13}

Research Team

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Bevacizumab (Monoclonal Antibodies)
• Casdozokitug (Other)
• Toripalimab (Checkpoint Inhibitor)

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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 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]

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]

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]

References

1. United States 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. [2022]

2. New Zealand 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. [2022]

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

Perioperative Bevacizumab-based Triplet Chemotherapy in Patients With Potentially Resectable Colorectal Cancer Liver Metastases. [2019]

4. Switzerland 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? [2021]

5. Greece pubmed.ncbi.nlm.nih.gov

Chemotherapy Plus Bevacizumab as Neoadjuvant or Conversion Treatment in Patients with Colorectal Liver Metastases. [2018]

6. 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]

7. United States 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. [2023]

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

Anlotinib Combined With Toripalimab as First-Line Therapy for Unresectable Hepatocellular Carcinoma: A Prospective, Multicenter, Phase II Study. [2023]

9. England 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. [2020]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Cost-effectiveness of toripalimab plus chemotherapy for advanced esophageal squamous cell carcinoma. [2023]

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

Impact of older age in patients receiving atezolizumab and bevacizumab for hepatocellular carcinoma. [2023]

12. Singapore pubmed.ncbi.nlm.nih.gov

Bevacizumab and atezolizumab as first-line therapy for advanced hepatocellular carcinoma: A Taiwanese subgroup analysis on efficacy and safety. [2022]

13. Greece pubmed.ncbi.nlm.nih.gov

Current Role of Atezolizumab Plus Bevacizumab Therapy in the Sequential Treatment of Unresectable Hepatocellular Carcinoma. [2022]