Immune Therapy + Bevacizumab for Advanced Liver Cancer

Recruiting at 38 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: MedImmune LLC

Must not be taking: Immunosuppressants, Chemotherapy

Disqualifiers: Hepatic encephalopathy, Gastrointestinal bleeding, 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: Until confirmed progressive disease or other discontinuation criteria

433 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a multicenter, open-label, stratified, randomized study to evaluate the safety, tolerability, antitumor activity, pharmacokinetics, pharmacodynamics, and immunogenicity of durvalumab or tremelimumab monotherapy, or durvalumab in combination with tremelimumab or bevacizumab in advanced hepatocellular carcinoma.

Research Team

MedImmune, LLC MedImmune, LLC

Principal Investigator

MedImmune LLC

Eligibility Criteria

This trial is for adults with advanced liver cancer who have either not responded to, cannot tolerate, or chose not to use sorafenib or similar drugs. It's also open to those who haven't had any systemic therapy for their cancer. People can't join if they've had certain complications like ascites needing intervention, hepatic encephalopathy, major blood vessel thrombosis in the liver, active autoimmune diseases, recent immunosuppressive meds use, or gastrointestinal bleeding within the last year.

Inclusion Criteria

I have liver cancer and cannot tolerate or have refused standard treatments.

I am at least 18 years old (20 if in Japan).

I have never received immunotherapy.

Exclusion Criteria

I've needed a procedure to remove excess belly fluid in the last 6 months.

I am not currently on any cancer treatments like chemotherapy or immunotherapy.

I haven't taken immunosuppressive drugs in the last 14 days, with some exceptions.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive various dosing regimens of durvalumab, tremelimumab, and bevacizumab based on the study part and cohort

Until confirmed progressive disease or other discontinuation criteria

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months after the first dose of study drug given to the last participant

Survival Follow-up

All participants will be followed for survival until the end of study visit

Until the last participant discontinues the study treatment

Treatment Details

Interventions

• Bevacizumab
• Durvalumab
• Tremelimumab

Trial Overview The study is testing different treatments: Durvalumab alone; Tremelimumab alone; and combinations of Durvalumab with Tremelimumab or Bevacizumab. The goal is to see how safe these treatments are and how well they work against advanced liver cancer by monitoring tumor response and changes in the body's immune system.

Participant Groups

Group I: Parts 2 and 3: Tremelimumab 750 mg Experimental Treatment 1 Intervention

Participants will receive tremelimumab 750 mg Q4W 7 doses followed by every 12 weeks (Q12W) until confirmed progressive disease, withdrawal of consent, lost to follow-up, or development of other reason for treatment discontinuation, whichever occurs first.

Group II: Parts 2 and 3: Tremelimumab 75 mg + Durvalumab 1500 mg Experimental Treatment 2 Interventions

Participants will receive tremelimumab 75 mg Q4W 4 doses and durvalumab 1500 mg Q4W until confirmed progressive disease, withdrawal of consent, lost to follow-up, or development of other reason for treatment discontinuation, whichever occurs first. Participant recruitment to this arm was closed following protocol amendment 5.

Group III: Parts 2 and 3: Tremelimumab 300 mg + Durvalumab 1500 mg Experimental Treatment 2 Interventions

Participants will receive tremelimumab 300 mg 1 dose and durvalumab 1500 mg Q4W until confirmed progressive disease, withdrawal of consent, lost to follow, or development of other reason for treatment discontinuation, whichever occurs first.

Group IV: Parts 2 and 3: Durvalumab 1500 mg Experimental Treatment 1 Intervention

Participants will receive durvalumab 1500 mg Q4W until confirmed progressive disease, withdrawal of consent, lost to follow-up, or development of other reason for treatment discontinuation, whichever occurs first.

Group V: Part 4: Durvalumab 1120 mg + Bevacizumab 15 mg/kg Experimental Treatment 2 Interventions

Participants will receive durvalumab 1120 mg and bevacizumab 15 mg/kg every 3 weeks (Q3W) until confirmed progressive disease, withdrawal of consent, lost to follow-up, or development of other reason for treatment discontinuation, whichever occurs first

Group VI: Part 1: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg Experimental Treatment 2 Interventions

Participants in Part 1A (safety run-in cohort) and Part 1 B (efficacy-gating cohort) will receive tremelimumab 1 mg/kg every 4 weeks (Q4W) 4 doses and durvalumab 20 mg/kg Q4W until confirmed progressive disease, withdrawal of consent, lost to follow-up, or development of other reason for treatment discontinuation, whichever occurs first.

Group VII: China Cohort: Tremelimumab 10 mg/kg Experimental Treatment 1 Intervention

Participants will receive tremelimumab 10 mg/kg Q4W 7 doses followed by Q12W until confirmed progressive disease, withdrawal of consent, lost to follow-up, or development of other reason for treatment discontinuation, whichever occurs first.

Group VIII: China Cohort: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg Experimental Treatment 2 Interventions

Participants will receive tremelimumab 1 mg/kg Q4W 4 doses and durvalumab 20 mg/kg Q4W until confirmed progressive disease, withdrawal of consent, lost to follow-up, or development of other reason for treatment discontinuation, whichever occurs first.

Group IX: China Cohort: Durvalumab 20 mg/kg Experimental Treatment 1 Intervention

Participants will receive durvalumab 20 mg/kg Q4W until confirmed progressive disease, withdrawal of consent, lost to follow-up, or development of other reason for treatment discontinuation, whichever occurs first.

Durvalumab is already approved in European Union, United States, Japan for the following indications:

Approved in European Union as Imfinzi for:

• Locally advanced, unresectable non-small cell lung cancer (NSCLC)

Approved in United States as Imfinzi for:

• Extensive-stage small cell lung cancer (ES-SCLC)
• Limited-stage small cell lung cancer (LS-SCLC)
• Locally advanced or metastatic urothelial carcinoma

Approved in Japan as Imfinzi for:

• Not specified in provided sources

Who Is Running the Clinical Trial?

MedImmune LLC

Lead Sponsor

Trials

348

Recruited

788,000+

Founded

1988

Headquarters

Gaithersburg, USA

Known For

Biologics research

Top Products

Synagis, FluMist

Dr. Reginald Seeto

MedImmune LLC

Chief Medical Officer since 2008

MD from University of Sydney, B.Sc. from University of Sydney

Peter Greenleaf

MedImmune LLC

Chief Executive Officer since 2006

MBA from St. Joseph’s University, B.S. from Western Connecticut State University