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

Trial Summary

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.

What data supports the effectiveness of the treatment Cemiplimab + Y-90 SIR-Spheres for liver metastases from breast cancer?

Research shows that Y-90 SIR-Spheres, a type of radiation therapy, have been effective in treating liver metastases from colorectal cancer, especially when other treatments have failed. This suggests potential benefits for similar liver metastases from breast cancer. ^{1 2 3 4 5}

Is the combination of Cemiplimab and Y-90 SIR-Spheres safe for humans?

Cemiplimab has been studied for safety in various cancers, showing mild and infrequent liver injury in some cases. It is generally considered to have a favorable safety profile, even in patients with pre-existing liver conditions. ^{6 7 8 9 10}

How is the treatment with Cemiplimab and Y-90 SIR-Spheres unique for liver metastases from breast cancer?

This treatment combines Cemiplimab, an immunotherapy drug, with Y-90 SIR-Spheres, a type of radioembolization that delivers targeted radiation directly to liver tumors. This approach is unique because it combines systemic immune activation with localized radiation, potentially offering a novel way to manage liver metastases from breast cancer that are resistant to other treatments. ^{2 11 12 13 14}

What is the purpose of this trial?

This phase II trial tests how well cemiplimab and transarterial radioembolization (TARE) with yttrium-90 (Y90) SIR-Spheres, registered trademark, works in treating breast cancer that has spread from where it first started (primary site) to the liver (metastatic). Immunotherapy with monoclonal antibodies, such as cemiplimab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. TARE is a treatment that uses radioactive microspheres, such as Y90 SIR-S Spheres, to both cause hepatic artery embolization and to deliver regional radiotherapy. Y90 SIR-S Spheres is an injectable form of the radioisotope yttrium Y 90 encapsulated in resin microspheres. When injected into the artery supplying the tumor, yttrium Y 90 resin microspheres block the tumor blood vessels and deliver the yttrium Y 90 directly to the tumor site, which may kill or slow tumor growth. 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.

Research Team

Jonathan Kessler

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Recommendations for SIR-Spheres Y-90 resin microspheres in chemotherapy-refractory/intolerant colorectal liver metastases. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Unresectable chemorefractory liver metastases: radioembolization with 90Y microspheres--safety, efficacy, and survival. [2022]

3. China pubmed.ncbi.nlm.nih.gov

A single institute retrospective trial of concurrent chemotherapy with SIR-Spheres® versus SIR-Spheres® alone in chemotherapy-resistant colorectal cancer liver metastases. [2020]

4. United States pubmed.ncbi.nlm.nih.gov

Yttrium 90 resin microspheres for the treatment of unresectable colorectal hepatic metastases after failure of multiple chemotherapy regimens: preliminary results. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Y-90 Radiomicrosphere Therapy for Colorectal Cancer Liver Metastases. [2016]

6. United States 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. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Infrequent liver injury from cemiplimab in patients with advanced cutaneous squamous cell carcinoma. [2022]

8. Germany pubmed.ncbi.nlm.nih.gov

Dose exploration results from Phase 1 study of cemiplimab, a human monoclonal programmed death (PD)-1 antibody, in Japanese patients with advanced malignancies. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

Pattern and impact of hepatic adverse events encountered during immune checkpoint inhibitors - A territory-wide cohort study. [2021]

10. United States 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. [2021]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Long-term radiological and histological outcomes following selective internal radiation therapy to liver metastases from breast cancer. [2022]

12. United States pubmed.ncbi.nlm.nih.gov

Regional yttrium-90 microsphere treatment of surgically unresectable and chemotherapy-refractory metastatic liver carcinoma. [2016]

13. Italy pubmed.ncbi.nlm.nih.gov

Yttrium-90 labelled resin microspheres for treatment of primary and secondary malignant liver tumors. [2009]

14. United States pubmed.ncbi.nlm.nih.gov

Radioembolization in patients with hepatic metastases from breast cancer. [2008]