Atezolizumab + Multi-Kinase Inhibitor for Liver Cancer
Recruiting in Palo Alto (17 mi)
+13 other locations
Overseen byWen Wee Ma
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Academic and Community Cancer Research United
Must be taking: Anti-HBV treatment
Must not be taking: Multi-kinase inhibitors, Immunosuppressants
Disqualifiers: Autoimmune disease, Brain metastasis, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This phase II trial tests whether atezolizumab in combination with a multi-kinase inhibitor (cabozantinib or lenvatinib) compared to multi-kinase inhibitor alone in treating patients with liver cancer that cannot be removed by surgery (unresectable), has spread to has spread to nearby tissue or lymph nodes (locally advanced), or has spread to other places in the body (metastatic), for which the patient has received treatment in the past (previously treated). Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Cabozantinib and lenvatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving atezolizumab with cabozantinib or lenvatinib may kill more tumor cells in patients with liver cancer.
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 certain medications like strong inducers or inhibitors of CYP3A4, you may need to stop them 14 days before starting the trial. It's best to discuss your current medications with the trial team.
What data supports the effectiveness of the drug combination Atezolizumab and Lenvatinib for liver cancer?
Research shows that Lenvatinib, a multikinase inhibitor, has been used for advanced liver cancer, and when combined with other immune therapies, it may enhance antitumor activity. Atezolizumab, when combined with other drugs, has been effective in treating liver cancer, suggesting potential benefits when used with Lenvatinib.
12345Is the combination of atezolizumab and multi-kinase inhibitors like lenvatinib safe for liver cancer patients?
The combination of atezolizumab with bevacizumab has been studied for safety in liver cancer patients, showing good overall survival, but lenvatinib alone has been evaluated for safety in patients unlikely to benefit from atezolizumab plus bevacizumab. Safety data specific to atezolizumab combined with multi-kinase inhibitors like lenvatinib is not directly available from the provided studies.
45678How is the drug combination of Atezolizumab, Cabozantinib, and Lenvatinib unique for liver cancer?
This drug combination is unique because it combines Atezolizumab, an immune system booster, with Cabozantinib and Lenvatinib, which are multi-kinase inhibitors that block cancer growth signals. This approach aims to enhance the body's immune response while simultaneously targeting cancer cell pathways, offering a novel strategy compared to existing treatments.
1391011Eligibility Criteria
This trial is for adults with advanced liver cancer that's inoperable, locally advanced, or metastatic and have previously been treated. Participants must be able to take oral meds, have a specific performance status (ECOG 0 or 1), and their liver function needs to meet certain criteria. Women of childbearing age must test negative for pregnancy and agree to use contraception.Inclusion Criteria
Consent to using archival tumor tissues, if available
Hemoglobin >= 90 g/L (9 g/dL)
My kidney function, measured by creatinine levels, is within the required range.
+23 more
Exclusion Criteria
Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab formulation
Other uncontrolled, significant intercurrent or recent illness including cardiovascular disorders, uncontrolled hypertensions, stroke, myocardial infarction, or other ischemic event =< 3 months prior to randomization, uncontrolled arrythmia, thromboembolic event =< 3 months prior to randomization, active bacterial infection requiring systemic treatment, known human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS) related illness, prior allogenic stem cell or solid organ transplantation, uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures, uncontrolled or symptomatic hypercalcemia, uncontrolled tumor-related pain, other malignancy(ies) =< 5 years prior to randomization, pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within at least 5 months after the last dose of study medication, uncontrolled hepatic encephalopathy occurring =< 6 weeks prior to randomization
I don't have any health issues that prevent me from taking new medications.
+14 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Patients receive atezolizumab IV and cabozantinib or lenvatinib PO in 21-day cycles, or cabozantinib or lenvatinib alone in 21-day cycles
21-day cycles, repeated until disease progression or unacceptable toxicity
Follow-up
Participants are monitored for safety and effectiveness after treatment
Every 9 weeks for up to 2 years
Participant Groups
The study tests atezolizumab combined with cabozantinib or lenvatinib against just the multi-kinase inhibitors alone. Atezolizumab is an immunotherapy drug while cabozantinib and lenvatinib block enzymes that help tumor cells grow. The goal is to see if combining these treatments works better for treating liver cancer.
2Treatment groups
Experimental Treatment
Active Control
Group I: Arm A (atezolizumab, cabozantinib or lenvatinib)Experimental Treatment3 Interventions
Patients receive atezolizumab IV over 30-60 minutes on day 1 and cabozantinib PO QD or lenvatinib PO QD on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Group II: Arm B (cabozantinib or lenvatinib)Active Control2 Interventions
Patients receive cabozantinib PO QD or lenvatinib PO QD on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Atezolizumab is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Tecentriq for:
- Melanoma
- Hepatocellular carcinoma
- Small cell lung cancer
- Non-small cell lung cancer
- Urothelial carcinoma
🇪🇺 Approved in European Union as Tecentriq for:
- Melanoma
- Hepatocellular carcinoma
- Small cell lung cancer
- Non-small cell lung cancer
- Urothelial carcinoma
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University Hospitals Cleveland Medical Center - Seidman Cancer CenterCleveland, OH
Mayo Clinic in ArizonaScottsdale, AZ
University of Chicago Comprehensive Cancer CenterChicago, IL
Carle Cancer Center NCI Community Oncology Research ProgramUrbana, IL
More Trial Locations
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Who Is Running the Clinical Trial?
Academic and Community Cancer Research UnitedLead Sponsor
National Cancer Institute (NCI)Collaborator
Genentech, Inc.Industry Sponsor
References
Phase Ib Study of Lenvatinib Plus Pembrolizumab in Patients With Unresectable Hepatocellular Carcinoma. [2022]The immunomodulatory effect of lenvatinib (a multikinase inhibitor) on tumor microenvironments may contribute to antitumor activity when combined with programmed death receptor-1 (PD-1) signaling inhibitors in hepatocellular carcinoma (HCC). We report results from a phase Ib study of lenvatinib plus pembrolizumab (an anti-PD-1 antibody) in unresectable HCC (uHCC).
EGFR activation limits the response of liver cancer to lenvatinib. [2023]Hepatocellular carcinoma (HCC)-the most common form of liver cancer-is an aggressive malignancy with few effective treatment options1. Lenvatinib is a small-molecule inhibitor of multiple receptor tyrosine kinases that is used for the treatment of patients with advanced HCC, but this drug has only limited clinical benefit2. Here, using a kinome-centred CRISPR-Cas9 genetic screen, we show that inhibition of epidermal growth factor receptor (EGFR) is synthetic lethal with lenvatinib in liver cancer. The combination of the EGFR inhibitor gefitinib and lenvatinib displays potent anti-proliferative effects in vitro in liver cancer cell lines that express EGFR and in vivo in xenografted liver cancer cell lines, immunocompetent mouse models and patient-derived HCC tumours in mice. Mechanistically, inhibition of fibroblast growth factor receptor (FGFR)  by lenvatinib treatment leads to feedback activation of the EGFR-PAK2-ERK5 signalling axis, which is blocked by EGFR inhibition. Treatment of 12 patients with advanced HCC who were unresponsive to lenvatinib treatment with the combination of lenvatinib plus gefitinib (trial identifier NCT04642547) resulted in meaningful clinical responses. The combination therapy identified here may represent a promising strategy for the approximately 50% of patients with advanced HCC who have high levels of EGFR.
Outcomes of Patients with Advanced Hepatocellular Carcinoma Receiving Lenvatinib following Immunotherapy: A Real World Evidence Study. [2023]Lenvatinib, a multikinase inhibitor, is an FDA-approved treatment for advanced hepatocellular carcinoma (HCC) in the first-line setting. Recent trial data have established atezolizumab plus bevacizumab as well as tremelimumab plus durvalumab as preferred first-line treatment options for advanced HCC. The role of lenvatinib following progression on immunotherapy in patients with advanced HCC remains unclear.
Comparison of Efficacy and Safety of Atezolizumab Plus Bevacizumab and Lenvatinib as First-Line Therapy for Unresectable Hepatocellular Carcinoma: A Propensity Score Matching Analysis. [2022]A comparison between atezolizumab plus bevacizumab (ATEZO/BEVA) and lenvatinib (LEN) for the treatment of hepatocellular carcinoma (HCC) remains unclear.
Clinical efficacy and safety of atezolizumab plus bevacizumab versus lenvatinib in the treatment of advanced hepatocellular carcinoma: A systematic review and meta-analysis. [2023]Assess the effectiveness and safety of treatment options atezolizumab plus bevacizumab (Atez/Bev) or lenvatinib in clinical practice for patients with advanced hepatocellular carcinoma (HCC) patients.
Atezolizumab plus bevacizumab versus lenvatinib for unresectable hepatocellular carcinoma: a large real-life worldwide population. [2023]Atezolizumab plus bevacizumab and lenvatinib have not been compared in a randomised controlled trial. We conducted a retrospective multi-centre study to compare the clinical efficacy and safety of lenvatinib and atezolizumab with bevacizumab as a first-line treatment for patients with unresectable HCC in the real-world scenario.
Comparing the impact of atezolizumab plus bevacizumab and lenvatinib on the liver function in hepatocellular carcinoma patients: A mixed-effects regression model approach. [2023]This retrospective study compared the impact of atezolizumab plus bevacizumab (Atez/Bev) and lenvatinib (LEN) on the liver function in patients with hepatocellular carcinoma.
Lenvatinib for Hepatocellular Carcinoma Patients with Nonviral Infection Who Were Unlikely to Respond to Immunotherapy: A Retrospective, Comparative Study. [2021]Atezolizumab plus bevacizumab (atezo + bev) shows a good overall survival (OS) in advanced hepatocellular carcinoma (HCC) patients. However, the OS of patients with nonviral infection is quite worse than that in those with viral infection. The present study investigated the efficacy and safety of lenvatinib in patients with nonviral infection, who were unlikely to obtain benefit from atezo + bev.
Rechallenge With Lenvatinib After Atezolizumab Plus Bevacizumab Treatment for Hepatocellular Carcinoma. [2022]Atezolizumab plus bevacizumab and lenvatinib are the key drugs in the current systemic chemotherapeutic regimen for hepatocellular carcinoma (HCC). Studies have reported the potential effectiveness of lenvatinib introduction after an atezolizumab plus bevacizumab treatment; however, the therapeutic effectiveness of a lenvatinib rechallenge after an atezolizumab plus bevacizumab treatment remains unclear.
Cabozantinib: A Review in Advanced Hepatocellular Carcinoma. [2020]Cabozantinib is an inhibitor of multiple receptor tyrosine kinases (RTKs) with roles in cancer pathogenesis. This review focuses on data relevant to the use of cabozantinib tablets (Cabometyx®) in the treatment of hepatocellular carcinoma (HCC) in patients who have been previously treated with the multi-RTK inhibitor sorafenib, an indication for which cabozantinib tablets are approved in the EU and USA. Approval of cabozantinib in this setting was based largely on the findings of CELESTIAL, a phase 3 trial in adults with advanced HCC who had previously received sorafenib, had progressive disease after at least one systemic therapy and had received up to two systemic treatments for their advanced disease. Compared with placebo in this study, cabozantinib prolonged both overall survival and progression-free survival, with these findings largely unaffected by patient/disease characteristics. The tolerability profile of cabozantinib in CELESTIAL was acceptable and consistent with that of other multi-RTK inhibitors, with adverse events that were manageable with dose modification and supportive care. Thus, cabozantinib is a welcome additional treatment option for use in adults with HCC previously treated with sorafenib.
Indirect Comparisons via Sorafenib for the Comparative Effectiveness of Two PD-1/PD-L1 Inhibitors to Treat Advanced Hepatocellular Carcinoma Patients without Prior Systemic Therapies. [2022]Advanced hepatocellular carcinoma (HCC) represents a major public health threat. Several emerging combination therapies have shown promising results for the first-line treatment of advanced HCC. The present study compared the efficacy of atezolizumab plus bevacizumab (AB) with lenvatinib plus pembrolizumab (LP), which were two of the leading combination therapies.