Therasphere + Systemic Therapy for Liver Cancer

Overseen By Study Coordinator

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Northwestern University

Must not be taking: PDL1, PD-1 antagonists

Disqualifiers: Autoimmune disease, CNS metastases, 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: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the effectiveness of two treatments for individuals with advanced liver cancer. Researchers aim to compare the efficacy of immunotherapy, which helps the immune system fight cancer, with tyrosine kinase inhibitors, medications that block cancer cell growth, following a special radiation treatment called Therasphere (Y90). Suitable candidates have liver cancer that cannot be treated with surgery or transplant. Participants may have received previous treatments but not prior cancer immunotherapy. As a Phase 2 trial, this study measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to important research.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop your current medications. However, you cannot be on any investigational agents, certain cancer therapies, or systemic glucocorticoids within specific timeframes before registration. It's best to discuss your current medications with the trial team.

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

Research has shown that combining Therasphere® (yttrium-90) with Atezolizumab and Bevacizumab is generally well-tolerated. One study found a low risk of severe side effects with this treatment. Another study with a small group of patients also found it safe and effective for treating advanced liver cancer.

For the combination of Therasphere® with Lenvatinib or Cabozantinib, studies indicate that Therasphere® therapy effectively controls liver tumors and is safe for patients whose liver cancer cannot be surgically removed.

Overall, these treatments have demonstrated a positive safety record in previous studies, suggesting they are well-tolerated by patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for liver cancer because they combine innovative approaches with existing systemic therapies. The Y90 + Atezolizumab and Bevacizumab treatment leverages radioembolization with Y90, a targeted internal radiation therapy, alongside immune checkpoint inhibitors, which may enhance the body's immune response to cancer cells. On the other hand, the Y90 + TKI arm incorporates tyrosine kinase inhibitors like Lenvatinib or Cabozantinib, aiming to disrupt cancer cell growth and blood supply more effectively. These combinations offer a potentially more potent attack on liver cancer compared to standard treatments, potentially leading to improved outcomes for patients.

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

Research has shown that using Therasphere® Y-90 (yttrium-90) with the drugs Atezolizumab and Bevacizumab, one of the treatment arms in this trial, holds promise for treating liver cancer. Earlier studies found this combination to be safe and effective, particularly for advanced liver cancer. Additionally, Y-90 radioembolization therapy alone has demonstrated better tumor control and greater safety compared to standard treatments.

Another treatment arm in this trial involves Y-90 combined with Lenvatinib or Cabozantinib. Studies have shown that Y-90 therapy significantly improves tumor control in liver cancer patients. Lenvatinib and Cabozantinib are standard treatments that slow cancer growth. Combining these with Y-90 may offer additional benefits by more precisely targeting cancer cells. ^{2 3 4 6 7}

Who Is on the Research Team?

Aparna Kalyan

Principal Investigator

Northwestern University

Are You a Good Fit for This Trial?

Adults with advanced hepatocellular carcinoma (liver cancer) who are not candidates for transplant or surgery. They must have a good performance status, measurable disease, and well-managed HIV or hepatitis if present. Women of childbearing age and sexually active men must use two contraception methods. Excluded are those with recent cancers, dialysis patients, untreated brain metastases, vaccine recipients within 28 days, pregnant/nursing women, allergy to trial drugs/components, prior PD-1/PD-L1 therapy users.

Inclusion Criteria

I have HIV and am on effective treatment.

I may or may not have received previous treatments for my condition.

I have liver cancer with a mild to moderate liver function score.

Exclusion Criteria

I have or had an autoimmune disease that could come back.

I have not received a live vaccine in the last 28 days.

I have brain metastases that have not been treated.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Therasphere® (Yttrium-90) Treatment

Participants receive liver-directed therapy with Therasphere® (Y-90) following institutional procedures

1 day

1 visit (in-person)

Recovery

Participants have a recovery period after Y-90 treatment before starting systemic therapy

2-3 weeks

Systemic Therapy

Participants receive systemic therapy with either immunotherapy (atezolizumab + bevacizumab) or TKI treatment (lenvatinib or cabozantinib)

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Atezolizumab and Bevacizumab
• Lenvatinib or Cabozantinib
• Y90

Trial Overview The study compares the effectiveness of Therasphere® (Y90 radiotherapy) followed by either immunotherapy (Atezolizumab + Bevacizumab) or tyrosine kinase inhibitors (Lenvatinib/Cabozantinib). The goal is to see which treatment better prevents liver cancer from progressing.

How Is the Trial Designed?

Group I: Y90 + TKI Experimental Treatment 1 Intervention

Group II: Y90 + Atezolizumab and Bevacizumab Experimental Treatment 1 Intervention

Atezolizumab and Bevacizumab is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Tecentriq and Avastin for:

• Hepatocellular carcinoma
• Non-small cell lung cancer
• Triple-negative breast cancer
• Urothelial carcinoma

Approved in European Union as Tecentriq and Avastin for:

• Hepatocellular carcinoma
• Non-small cell lung cancer
• Triple-negative breast cancer
• Urothelial carcinoma

Approved in Canada as Tecentriq and Avastin for:

• Hepatocellular carcinoma
• Non-small cell lung cancer
• Triple-negative breast cancer
• Urothelial carcinoma

Approved in Japan as Tecentriq and Avastin for:

• Hepatocellular carcinoma
• Non-small cell lung cancer
• Triple-negative breast cancer
• Urothelial carcinoma

Who Is Running the Clinical Trial?

Northwestern University

Lead Sponsor

Trials

1,674

Recruited

989,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Atezolizumab plus bevacizumab significantly improves progression-free survival (PFS) compared to lenvatinib in patients with unresectable hepatocellular carcinoma (uHCC), based on a meta-analysis of 8 studies involving 3690 patients.

Patients receiving atezolizumab plus bevacizumab experience fewer severe adverse events (grade 3/4) compared to those treated with lenvatinib, indicating a better safety profile, although lenvatinib may be more effective for overall survival in non-viral patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of atezolizumab plus bevacizumab versus lenvatinib for unresectable hepatocellular carcinoma: a systematic review and meta-analysis. Liu, J., Yang, L., Wei, S., et al.[2023]

In a review of 8 studies comparing atezolizumab plus bevacizumab (ATE/BEV) to lenvatinib (LEN) for advanced hepatocellular carcinoma, both treatments showed similar effectiveness in terms of objective response rate (ORR) and disease control rate (DCR).

While LEN was found to be non-inferior to ATE/BEV regarding progression-free survival (PFS), it may carry a higher risk of adverse events, suggesting that while both treatments are effective, LEN could lead to more side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab plus bevacizumab versus lenvatinib as first-line therapy for advanced hepatocellular carcinoma: A systematic review and meta-analysis. Giri, S., Angadi, S., Vaidya, A., et al.[2023]

In a study of 2205 patients with unresectable HCC, there was no significant overall survival advantage for atezolizumab plus bevacizumab compared to lenvatinib, indicating similar efficacy in first-line treatment.

However, the safety profile favored atezolizumab plus bevacizumab, as it had fewer adverse events, and specific patient groups showed differential benefits, with lenvatinib being more effective for those with non-alcoholic fatty liver disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab plus bevacizumab versus lenvatinib for unresectable hepatocellular carcinoma: a large real-life worldwide population. Casadei-Gardini, A., Rimini, M., Tada, T., et al.[2023]

In a study of 139 advanced hepatocellular carcinoma (HCC) patients treated with lenvatinib, the efficacy in terms of objective response rate and progression-free survival was similar for patients with viral and nonviral infections, indicating that lenvatinib is effective regardless of the infection type.

The 1-year survival rates were 68.7% for patients with viral infections and 59.5% for those with nonviral infections, suggesting that while there is a difference in survival rates, lenvatinib remains a viable treatment option for both groups without significant differences in treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenvatinib for Hepatocellular Carcinoma Patients with Nonviral Infection Who Were Unlikely to Respond to Immunotherapy: A Retrospective, Comparative Study. Hatanaka, T., Kakizaki, S., Nagashima, T., et al.[2021]

In a systematic review of 8 studies involving 6628 patients with advanced hepatocellular carcinoma (HCC), no significant differences in overall survival (OS) or progression-free survival (PFS) rates were found between the treatment options of atezolizumab plus bevacizumab (Atez/Bev) and lenvatinib.

However, Atez/Bev was more beneficial for patients with HCC caused by viral hepatitis, while lenvatinib showed better outcomes for patients with Child-Pugh class B liver function, indicating that treatment effectiveness may vary based on patient characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical efficacy and safety of atezolizumab plus bevacizumab versus lenvatinib in the treatment of advanced hepatocellular carcinoma: A systematic review and meta-analysis. Du, S., Cao, K., Wang, Z., et al.[2023]

In a study of 92 patients with unresectable hepatocellular carcinoma (HCC), lenvatinib showed similar efficacy to the combination of atezolizumab and bevacizumab (A+B) in terms of objective response rate, progression-free survival, and overall survival, indicating that both treatments are viable first-line options.

The safety profiles of lenvatinib and A+B were comparable, with similar rates of adverse events and minimal impact on liver function, suggesting that both therapies are safe for patients with HCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Similar efficacy and safety between lenvatinib versus atezolizumab plus bevacizumab as the first-line treatment for unresectable hepatocellular carcinoma. Su, CW., Teng, W., Lin, PT., et al.[2023]

In a study of 66 Taiwanese patients with advanced-stage hepatocellular carcinoma (HCC), those treated with lenvatinib showed a higher objective response rate (ORR) of 36.4% compared to 11.4% for sorafenib, indicating better efficacy for lenvatinib.

Both treatments resulted in similar median overall survival (OS) times (9.36 months for lenvatinib vs. 8.36 months for sorafenib), but patients on lenvatinib who achieved an objective tumor response had a significantly improved OS of 11.29 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Lenvatinib and Sorafenib in the Real-World First-Line Treatment of Advanced-Stage Hepatocellular Carcinoma in a Taiwanese Population. Lee, SW., Yang, SS., Lien, HC., et al.[2022]

In a study of 13 patients, rechallenging with lenvatinib after treatment with atezolizumab plus bevacizumab showed anti-tumor effects, but the duration of the second lenvatinib treatment was significantly shorter (2.8 months) compared to the first treatment (8.7 months).

While lenvatinib re-administration can be effective, it may lead to deterioration in liver function, highlighting the need for careful monitoring of liver health and patient status during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rechallenge With Lenvatinib After Atezolizumab Plus Bevacizumab Treatment for Hepatocellular Carcinoma. Komatsu, S., Yano, Y., Kido, M., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37988840/

Efficacy of transarterial radioembolization using Y-90 resin ... In HCC patients receiving treatment, TARE using Y-90 resin microspheres may achieve comparable effectiveness outcomes compared with AB.

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.e16231

Introducing yttrium-90 radioembolization to atezolizumab ... This small patient cohort demonstrated preliminary safety and effectiveness of TARE in combination with Atezo/Bev in treating intermediate and advanced stage ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0973688323008757/pdf

Efficacy of Yttrium-90 Transarterial Radioembolisation in ... This was a retrospective study of primary liver cancer cases in which the TARE procedure was done from November 2017 to December 2021. Glass-based Y-90 ...

4. bostonscientific.com bostonscientific.com/content/dam/bsc/us/pi/ir/ioe/therasphere/campaign/clinical/downloads/DOSISPHERE-01_datasheet_PI-750208-AE.pdf

THERASPHERE™ Y-90 Glass Microspheres Updated efficacy and safety data from IMbrave150: atezolizumab plus bevacizumab vs. sorafenib for unresectable hepatocellular carcinoma. J ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04541173

Study of Atezolizumab and Bevacizumab With Y-90 TARE ... This is an open-label, multi-center, randomized phase II study comparing the Y90 TARE followed by bevacizumab and atezolizumab treatment to the Y90 TARE ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10742675/

Safety and Efficacy of Concurrent Atezolizumab/ ... The utilization of Y90-RE concurrently or within 90 days of nivolumab or atezolizumab/bevacizumab immunotherapy, appears to be well-tolerated and with a low ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.TPS4221

EMERALD-Y90: TARE + durvalumab/bevacizumab for uHCC pts The EMERALD-Y90 study will evaluate the efficacy and safety of TARE with D monotherapy, followed by D + B in pts with uHCC eligible for embolization.