TARE + Durvalumab + Bevacizumab for Liver Cancer

(EMERALD-Y90 Trial)

Recruiting in Palo Alto (17 mi)

+19 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: AstraZeneca

Disqualifiers: Curative surgery, HBV and HDV, Cardiovascular, Hypertension, Thrombotic event, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

The purpose of this study is to measure the efficacy and safety of durvalumab intravenous (IV) solution plus bevacizumab IV solution after transarterial radioembolization (Yttrium 90 glass microspheres TARE) in participants with unresectable hepatocellular carcinoma (HCC) amenable to embolization.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Bevacizumab, when used in combination with chemotherapy, has been shown to improve survival in patients with metastatic colorectal cancer, which sometimes involves the liver. This suggests it may have potential benefits for liver cancer treatment as well. ^{1 2 3 4 5}

Is the combination of TARE, Durvalumab, and Bevacizumab generally safe for humans?

Bevacizumab, one of the drugs in the combination, has been associated with side effects like bleeding, high blood pressure, and blood clots in various cancer treatments. However, it has been generally well-tolerated in some studies, with serious side effects occurring in about 10% of patients. There is no specific safety data available for the combination of TARE, Durvalumab, and Bevacizumab. ^{6 7 8 9 10}

How is the drug combination of TARE, Durvalumab, and Bevacizumab unique for liver cancer treatment?

This treatment is unique because it combines TARE (a type of radiation therapy) with Durvalumab, an immune checkpoint inhibitor that enhances the body's immune response against cancer, and Bevacizumab, which inhibits blood vessel growth in tumors. This combination aims to target liver cancer through multiple mechanisms, potentially offering a novel approach compared to standard treatments. ^{11 12 13 14 15}

Research Team

Eligibility Criteria

This trial is for adults with unresectable liver cancer (HCC) who can undergo TARE, have a Child-Pugh score class A (indicating good liver function), no cancer outside the liver, at least one measurable tumor in the liver, and are generally in good health or only mildly ill. They must also meet specific criteria for lung safety during treatment and have enough healthy liver tissue.

Inclusion Criteria

My liver function is mildly affected.

I have a measurable tumor and am eligible for a specific radiation therapy.

My liver cancer cannot be removed with surgery.

Exclusion Criteria

I have not had a heart attack, stroke, or similar event in the last 6 months.

I have had treatment for liver cancer that couldn't be removed by surgery.

I haven't had any major stomach or intestine issues, like bleeding or unhealed ulcers, in the last 6 months.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 visit (in-person)

Transarterial Radioembolization (TARE)

Participants undergo Yttrium 90 glass microspheres TARE according to the dosimetry recommendation

1 day

1 visit (in-person)

Treatment

Participants receive durvalumab monotherapy followed by durvalumab + bevacizumab

Approximately 3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

90 days after the last dose of study drug

Treatment Details

Interventions

• Bevacizumab (Monoclonal Antibodies)
• Durvalumab (Checkpoint Inhibitor)
• Transarterial Radioembolization (TARE) (Radiation)

Trial Overview The study tests if combining Durvalumab (an IV drug) and Bevacizumab (another IV drug) after Transarterial Radioembolization (TARE using Yttrium 90 microspheres) improves outcomes for patients with HCC that cannot be surgically removed. The effectiveness and safety of this combination therapy are being evaluated.

Participant Groups

Group I: Yttrium 90 glass microspheres TARE in combination with Durvalumab and Bevacizumab Experimental Treatment 3 Interventions

Participants will undergo Yttrium 90 glass microspheres TARE according to the dosimetry recommendation.

Bevacizumab is already approved in Japan, Canada for the following indications:

Approved in Japan as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Breast cancer
• Renal cell carcinoma
• Ovarian cancer

Approved in Canada as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Breast cancer
• Renal cell carcinoma
• Ovarian cancer

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Findings from Research

In a phase II study involving 66 patients with previously treated metastatic colorectal cancer, dilpacimab combined with FOLFIRI resulted in a median progression-free survival of only 3.78 months, significantly shorter than the 7.36 months seen with bevacizumab plus FOLFIRI.

Dilpacimab treatment was associated with serious adverse events, including one fatal intestinal perforation, highlighting its poor tolerability compared to bevacizumab, which had no reported serious side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of dilpacimab (ABT-165) versus bevacizumab plus FOLFIRI in metastatic colorectal cancer: a phase II study. Strickler, JH., Cubillo, A., Liang, JT., et al.[2022]

In a study of six patients with unresectable colorectal cancer treated with bevacizumab, the combination chemotherapy was well-tolerated, with most adverse drug reactions being grade 2 or less.

Only one patient experienced grade 3 neutropenia, and there were no specific adverse effects directly related to bevacizumab, suggesting it can be safely used in combination with chemotherapy for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A clinical experience in treatment with bevacizumab for unresectable colorectal cancer]. Fujimoto, T., Yoshimatsu, K., Yokomizo, H., et al.[2016]

Durvalumab, a PD-L1 blocking antibody, has shown clinical efficacy and a manageable safety profile in treating advanced non-small-cell lung cancer, especially in patients with ≥25% PD-L1 expression.

The drug is being evaluated in various treatment settings, including as a monotherapy and in combination with other therapies, showing promising results particularly after chemoradiation, although lower response rates were noted in patients with EGFR and ALK mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab in non-small-cell lung cancer patients: current developments. Mezquita, L., Planchard, D.[2018]

Durvalumab is an FDA-approved monoclonal antibody that enhances T-cell responses against cancer by blocking the PD-L1 pathway, specifically for patients with advanced urothelial carcinoma who have progressed after platinum-based chemotherapy.

The drug is currently being tested in phase III trials for various cancers, including lung and head and neck cancers, indicating its potential broad application in oncology beyond urothelial carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab: First Global Approval. Syed, YY.[2022]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Bevacizumab in combination with FOLFIRI chemotherapy in patients with metastatic colorectal cancer: an assessment of safety and efficacy in the province of Newfoundland and Labrador. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of dilpacimab (ABT-165) versus bevacizumab plus FOLFIRI in metastatic colorectal cancer: a phase II study. [2022]

3. England pubmed.ncbi.nlm.nih.gov

The combination of FOLFOX4 and bevacizumab may enable salvage surgery of unresectable liver metastases in colon cancer. [2009]

4. Germany pubmed.ncbi.nlm.nih.gov

Effect of bevacizumab in older patients with metastatic colorectal cancer: pooled analysis of four randomized studies. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Phase IV study of bevacizumab in combination with infusional fluorouracil, leucovorin and irinotecan (FOLFIRI) in first-line metastatic colorectal cancer. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Bevacizumab in Cancer Patients with Inflammatory Bowel Disease. [2022]

7. Germany pubmed.ncbi.nlm.nih.gov

Comparative safety profiles of intravitreal bevacizumab, ranibizumab and pegaptanib: the analysis of the WHO database of adverse drug reactions. [2022]

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

FDA drug approval summary: bevacizumab plus interferon for advanced renal cell carcinoma. [2021]

9. Japan pubmed.ncbi.nlm.nih.gov

[A clinical experience in treatment with bevacizumab for unresectable colorectal cancer]. [2016]

10. England pubmed.ncbi.nlm.nih.gov

Bevacizumab in clinical practice: prescribing appropriateness relative to national indications and safety. [2021]

11. England pubmed.ncbi.nlm.nih.gov

A multicenter, phase Ib/II, open-label study of tivozanib with durvalumab in advanced hepatocellular carcinoma (DEDUCTIVE). [2023]

12. England pubmed.ncbi.nlm.nih.gov

Durvalumab in non-small-cell lung cancer patients: current developments. [2018]

13. New Zealand pubmed.ncbi.nlm.nih.gov

Safety and efficacy of durvalumab (MEDI4736) in various solid tumors. [2022]

14. New Zealand pubmed.ncbi.nlm.nih.gov

Durvalumab: First Global Approval. [2022]

15. Switzerland pubmed.ncbi.nlm.nih.gov

Liver injury during durvalumab-based immunotherapy is associated with poorer patient survival: A retrospective analysis. [2023]