Cemiplimab + Y-90 SIR-Spheres for Liver Metastases from Breast Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: City of Hope Medical Center

Must not be taking: Immunosuppressants, Anti-PD-1/PD-L1

Disqualifiers: Autoimmune disease, Hepatitis, HIV, 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

Compensation: Varies

Number of Visits: 51

Duration: Up to 1 year

11 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment approach for breast cancer that has spread to the liver. It combines cemiplimab, a drug that may help the immune system attack cancer cells, with a targeted radiation treatment called TARE using Y90 SIR-Spheres (tiny radioactive spheres). This combination aims to kill or slow the growth of cancer in the liver. Individuals with breast cancer that has spread to the liver and who have already tried chemotherapy might be suitable candidates for this study. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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

The trial protocol does not specify if you need to stop taking your current medications. However, you must not have received any anticancer therapy within 28 days before the first dose of the study drug, and certain medications like immunosuppressive drugs are not allowed. It's best to discuss your specific medications with the study team.

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

Previous studies have found cemiplimab, a type of immunotherapy, to be generally safe. Among 60 patients with advanced solid tumors, no serious side effects occurred, indicating a positive safety profile. However, 91% of patients experienced treatment-related side effects, mostly mild.

For Y-90 SIR-Spheres used in transarterial radioembolization (TARE), research has shown that this treatment is usually well-tolerated. It proved safe for patients with breast cancer that had spread to the liver, with most experiencing no severe side effects. Additionally, the treatment controlled liver disease in about 70% of cases.

Both treatments have been studied separately and have shown promising safety results. However, combining them might present new challenges. Still, available data suggests that both are generally well-tolerated. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using cemiplimab combined with Y-90 SIR-Spheres for liver metastases from breast cancer because it represents a novel approach by pairing immunotherapy with targeted radiation. Cemiplimab is an immune checkpoint inhibitor that unleashes the body's immune system to attack cancer cells, a mechanism different from traditional chemotherapy. The Y-90 SIR-Spheres deliver precise radiation directly to the tumor, minimizing damage to surrounding healthy tissue. This combination aims to enhance the treatment's efficacy while potentially reducing side effects compared to conventional therapies.

What evidence suggests that cemiplimab and Y-90 SIR-Spheres might be effective for liver metastases from breast cancer?

Research has shown that cemiplimab, a monoclonal antibody, effectively aids individuals with various cancers. In some studies, cemiplimab significantly reduced the risk of cancer recurrence or death, with one study indicating a 68% reduction. Additionally, transarterial radioembolization (TARE) using Y-90 SIR-Spheres has shown promise in managing liver tumors, achieving a 70% success rate in controlling cancer in patients with breast cancer that has spread to the liver. In this trial, participants will receive both cemiplimab and TARE as part of the treatment regimen. Cemiplimab enhances the immune system's ability to fight cancer, while TARE delivers targeted radiation to the tumors. Together, these treatments aim to destroy tumors more effectively and improve patient outcomes. ^{2 3 4 5 6}

Who Is on the Research Team?

Jonathan Kessler

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

This trial is for individuals with breast cancer that has spread to the liver. Participants should have a type of breast cancer suitable for this treatment and must be able to undergo procedures like CT scans, MRIs, biopsies, and radioembolization.

Inclusion Criteria

I do not have cirrhosis.

International normalized ration (INR) ≤ 1.6

Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) ≤ 5 x upper limit of normal (ULN)

Exclusion Criteria

I have received immunotherapy within the last year.

I am not pregnant, breastfeeding, and willing to use birth control if of childbearing potential.

My cancer has spread to the vein leading to my liver.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive cemiplimab intravenously every 21 days and Y90 SIR-Spheres via TARE on days 7-14 and day 67

Up to 1 year

Cemiplimab every 21 days, TARE on days 7-14 and day 67

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

30 days post-treatment, every 3 months within 1 year, then every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Cemiplimab
• Transarterial Radioembolization with Y-90 SIR-S Spheres

Trial Overview

The study is testing the combination of cemiplimab (an immune system-boosting drug) with Y90 SIR-Spheres (radioactive microspheres) delivered directly into the liver's blood vessels to treat metastatic breast cancer in the liver.

How Is the Trial Designed?

Group I: Treatment (cemiplimab, Y90 SIR-Spheres, TARE) Experimental Treatment 7 Interventions

Patients receive cemiplimab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 days for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients receive Y90 SIR-Spheres intratumorally via TARE over 60-90 minutes once during days 7-14 and on day 67. Patients also undergo tumor biopsy at baseline and at day 42 after immunotherapy begins. Additionally patients also undergo blood sample collection and CT or MRI throughout the study.

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Cemiplimab, an anti-PD-1 monoclonal antibody, demonstrated a favorable safety profile in a study of 60 patients with advanced solid tumors, with no dose-limiting toxicities and manageable treatment-emergent adverse events like fatigue and nausea.

The treatment showed promising antitumor activity, with 2 complete responses and 7 partial responses, and responses lasting at least 12 months in some patients, indicating its potential effectiveness when combined with hypofractionated radiotherapy and/or cyclophosphamide.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-In-Human Study of Cemiplimab Alone or In Combination with Radiotherapy and/or Low-dose Cyclophosphamide in Patients with Advanced Malignancies. Papadopoulos, KP., Johnson, ML., Lockhart, AC., et al.[2021]

In a study of 1480 cancer patients treated with immune checkpoint inhibitors (ICIs), over 50% experienced hepatic adverse events (AEs), with 14.9% classified as severe (grade 3-4).

The presence of hepatic AEs was linked to poorer overall survival rates, with median survival dropping from 9.0 months for patients without AEs to just 3.3 months for those with severe hepatic AEs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pattern and impact of hepatic adverse events encountered during immune checkpoint inhibitors - A territory-wide cohort study. Chan, SL., Yip, TC., Wong, VW., et al.[2021]

Cemiplimab, administered as monotherapy or in combination with hypofractionated radiation therapy, showed a 10% objective response rate in patients with recurrent or metastatic cervical cancer, particularly in those with squamous histology, indicating its potential efficacy in this subgroup.

The most common side effects were diarrhea, fatigue, and hypokalemia, affecting 35%, 25%, and 25% of patients respectively, suggesting that while cemiplimab has anti-tumor activity, it also has a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PD-1 blockade in recurrent or metastatic cervical cancer: Data from cemiplimab phase I expansion cohorts and characterization of PD-L1 expression in cervical cancer. Rischin, D., Gil-Martin, M., González-Martin, A., et al.[2021]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06860815

Study Details | NCT06860815 | Cemiplimab and ...

Giving cemiplimab and Y90 SIR-Spheres by TARE to the tumor in the liver may kill more tumor cells in patients with metastatic breast cancer. Detailed ...

2.

targetedonc.com

targetedonc.com/view/unpacking-the-data-behind-adjuvant-cemiplimab-s-fda-approval

Unpacking the Data Behind Adjuvant Cemiplimab's FDA ...

The 24-month DFS rates for cemiplimab and placebo treatment were 87.1% and 64.1%, respectively. This effect was observed across all tumor ...

3.

withpower.com

withpower.com/trial/cemiplimab-y-90-sir-spheres-for-liver-metastases-from-breast-cancer-12f35

Cemiplimab + Y-90 SIR-Spheres for Liver Metastases from ...

Cemiplimab, administered as monotherapy or in combination with hypofractionated radiation therapy, showed a 10% objective response rate in patients with ...

4.

onclive.com

onclive.com/view/dr-rischin-on-the-efficacy-of-adjuvant-cemiplimab-in-high-risk-cscc

Dr Rischin on the Efficacy of Adjuvant Cemiplimab in High ...

The 2-year DFS rate was 87.1% in the cemiplimab arm vs 64.1% in the placebo arm. The benefit of adjuvant cemiplimab was observed across all ...

5.

newsroom.regeneron.com

newsroom.regeneron.com/news-releases/news-release-details/libtayor-cemiplimab-phase-3-data-adjuvant-treatment-post

Libtayo® (cemiplimab) Phase 3 Data in the Adjuvant ...

Libtayo demonstrated a 68% reduction in the risk of disease recurrence or death, the primary endpoint of the trial (p<0.0001).

6.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06860815

Study Details | NCT06860815 | Cemiplimab and ...

Giving cemiplimab and Y90 SIR-Spheres by TARE to the tumor in the liver may kill more tumor cells in patients with metastatic breast cancer. Detailed ...