Atezolizumab + Pertuzumab + Trastuzumab for Breast Cancer with Brain Metastases

Recruiting at 1 trial location

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Nancy Lin, MD

Must not be taking: High-dose corticosteroids, Immunosuppressants

Disqualifiers: Visceral crisis, Leptomeningeal metastases, Uncontrolled illness, 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: 33

Duration: 24 weeks

19 Participants Needed

Trial Summary

What is the purpose of this trial?

This research study is studying a drug called atezolizumab as a possible treatment HER2-positive metastatic breast cancer (MBC) that has spread to the brain. The names of the study drugs involved in this study are: * Atezolizumab * Pertuzumab * Trastuzumab

Will I have to stop taking my current medications?

The trial does not allow the use of other anti-cancer therapies during the study, but supportive care medications like pain medications are allowed. If you are on endocrine therapy, you may continue it if you have been on it within 28 days of starting the study, but you cannot start a new endocrine therapy during the trial.

What data supports the effectiveness of the drug combination Atezolizumab, Tecentriq, Pertuzumab, Perjeta, Trastuzumab, Herceptin, Trazimera, Herzuma, Ontruzant for breast cancer with brain metastases?

Research shows that pertuzumab and trastuzumab, when used together, can improve survival in patients with HER2-positive breast cancer, and trastuzumab has shown potential activity in treating brain metastases. These findings suggest that combining these drugs could be beneficial for treating breast cancer with brain metastases. ^{1 2 3 4 5}

What safety information is available for the combination of Atezolizumab, Pertuzumab, and Trastuzumab in treating breast cancer?

Pertuzumab, when used with Trastuzumab and another drug, has been studied for safety in breast cancer treatment. Common side effects include diarrhea, hair loss, low white blood cell count, nausea, tiredness, rash, and nerve damage. No additional heart-related side effects were noted. ^{6 7 8 9 10}

How is the drug combination of Atezolizumab, Pertuzumab, and Trastuzumab unique for treating breast cancer with brain metastases?

This drug combination is unique because it includes Atezolizumab, an immunotherapy that helps the immune system attack cancer cells, alongside Pertuzumab and Trastuzumab, which are known for targeting HER2-positive breast cancer. While Pertuzumab and Trastuzumab are standard for HER2-positive breast cancer, their combined use with Atezolizumab for brain metastases is novel and not yet well-studied, offering a potentially new approach for patients with this condition. ^{2 3 11 12 13}

Research Team

Nancy Lin

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

This trial is for adults with HER2-positive metastatic breast cancer that has spread to the brain. Participants must be in good physical condition (ECOG 0 or 1), not pregnant, and agree to use contraception. They can't have had major surgery recently, be on high-dose steroids or immunosuppressants, have certain other cancers or infections, or have received some treatments within specific time frames.

Inclusion Criteria

Eligibility will be assessed as part of the screening procedures for all patients.

I've been on a stable dose of dexamethasone (2mg or less) for at least a week.

My cancer has spread to my brain and is getting worse.

Exclusion Criteria

I am allergic or have had a bad reaction to trastuzumab, pertuzumab, or atezolizumab.

My cancer has spread to the brain or its coverings.

I have previously received treatments targeting the immune system.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive atezolizumab, pertuzumab, and trastuzumab for the treatment of CNS metastases in HER2-positive breast cancer

24 weeks

Weekly visits for the first 24 weeks, then every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 weeks

Every 9 weeks

Treatment Details

Interventions

• Atezolizumab
• Pertuzumab
• Trastuzumab

Trial Overview The study tests atezolizumab combined with pertuzumab and trastuzumab as a treatment for breast cancer that has metastasized to the brain. It's assessing how well these drugs work together and their safety in patients who meet strict eligibility criteria regarding health status and previous treatments.

Participant Groups

Group I: ATEZOLIZUMAB, PERTUZUMAB, TRASTUZUMAB Experimental Treatment 3 Interventions

Patients will receive the following treatment: * Atezolizumab (IV) every 3 weeks (q3w)\] * Pertuzumab (loading dose ), followed q3w thereafter by a predetermined dose in the protocol via IV) * High-dose Trastuzumab weekly for the first 24 weeks, and thereafter trastuzumab q3w).

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

Approved in United States as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Approved in European Union as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Who Is Running the Clinical Trial?

Nancy Lin, MD

Lead Sponsor

Trials

4

Recruited

160+

Genentech, Inc.

Industry Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Findings from Research

HER2-positive breast cancer, which historically had a poor prognosis, can now be effectively treated with a variety of anti-HER2 therapies, significantly improving patient survival rates.

Newly developed treatments, including trastuzumab deruxtecan and trastuzumab emtansine, along with ongoing clinical trials, are expanding options for patients with advanced HER2-positive breast cancer, raising important questions about the best treatment sequences and combinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-HER2 Drugs for the Treatment of Advanced HER2 Positive Breast Cancer. Stanowicka-Grada, M., Senkus, E.[2023]

In a review of six studies involving 996 patients with HER2-positive breast cancer, the addition of pertuzumab to trastuzumab emtansine (T-DM1) ± taxane did not significantly improve objective response or clinical benefit rates compared to T-DM1 alone.

While the combination treatment was associated with increased risks of certain adverse events like diarrhea and rash, it also showed a decreased risk of thrombocytopenia, indicating a complex safety profile that requires careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of the addition of pertuzumab to T-DM1 ± taxane in patients with HER2-positive, locally advanced or metastatic breast cancer: a pooled analysis. Zhang, J., Li, J., Zhu, C., et al.[2022]

A comprehensive analysis of 14,707 adverse events related to pertuzumab from the FDA Adverse Event Reporting System revealed significant safety concerns, including potential risks of myelosuppression, cardiotoxicity, and other serious conditions occurring in 12 organ systems.

Most adverse events, particularly cardiac-related issues, were reported within the first month of therapy, highlighting the need for careful monitoring and preparedness for emergency interventions, especially in elderly patients and those with pre-existing cardiovascular conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A disproportionality analysis of adverse events associated to pertuzumab in the FDA Adverse Event Reporting System (FAERS). Zou, SP., Yang, HY., Ouyang, ML., et al.[2023]

Pertuzumab, a monoclonal antibody targeting HER2, significantly improves progression-free survival in patients with HER2-positive metastatic breast cancer, with a median of 18.5 months compared to 12.4 months for the placebo group, based on a phase III trial with previously untreated patients.

While the overall safety profile of pertuzumab is similar to placebo, it is associated with a higher incidence of specific side effects such as diarrhea, rash, and neutropenia, indicating the need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The European Medicines Agency Review of Pertuzumab for the treatment of adult patients with HER2-positive metastatic or locally recurrent unresectable breast cancer: summary of the scientific assessment of the committee for medicinal products for human use. Boix-Perales, H., Borregaard, J., Jensen, KB., et al.[2023]

Pertuzumab is an effective treatment for metastatic HER2-positive breast cancer, especially when combined with trastuzumab and docetaxel, showing significant improvements in progression-free and overall survival in treatment-naive patients.

As a HER dimerization inhibitor, pertuzumab works differently than trastuzumab, allowing for a more complete blockade of HER2 signaling, and has a tolerable safety profile, making it a recommended first-line therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pertuzumab for the treatment of human epidermal growth factor receptor type 2-positive metastatic breast cancer. Chung, C., Lam, MS.[2019]

In a case study of a woman with HER2-positive metastatic breast cancer, the continuation of trastuzumab alongside systemic chemotherapy led to multiple treatment responses and prolonged survival despite the presence of brain metastases.

This suggests that trastuzumab may not only help control systemic disease but could also have a direct beneficial effect on brain metastases, which is a novel finding in the treatment of this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HER2-positive breast cancer brain metastases: multiple responses to systemic chemotherapy and trastuzumab--a case report. Church, DN., Bahl, A., Jones, A., et al.[2018]

References

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

Anti-HER2 Drugs for the Treatment of Advanced HER2 Positive Breast Cancer. [2023]

2. Netherlands pubmed.ncbi.nlm.nih.gov

HER2-positive metastatic breast cancer: a changing scenario. [2019]

3. Japan pubmed.ncbi.nlm.nih.gov

Clinical outcome of patients with isolated central nervous system progression on first-line pertuzumab and trastuzumab treatment for HER2-positive metastatic breast cancer in a real-life cohort. [2023]

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

Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer. [2022]

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

Safety and efficacy of the addition of pertuzumab to T-DM1 ± taxane in patients with HER2-positive, locally advanced or metastatic breast cancer: a pooled analysis. [2022]

6. England pubmed.ncbi.nlm.nih.gov

A disproportionality analysis of adverse events associated to pertuzumab in the FDA Adverse Event Reporting System (FAERS). [2023]

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

First FDA approval of dual anti-HER2 regimen: pertuzumab in combination with trastuzumab and docetaxel for HER2-positive metastatic breast cancer. [2018]

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

The European Medicines Agency Review of Pertuzumab for the treatment of adult patients with HER2-positive metastatic or locally recurrent unresectable breast cancer: summary of the scientific assessment of the committee for medicinal products for human use. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Pertuzumab for the treatment of human epidermal growth factor receptor type 2-positive metastatic breast cancer. [2019]

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

Phase 1b/2a study of trastuzumab emtansine (T-DM1), paclitaxel, and pertuzumab in HER2-positive metastatic breast cancer. [2022]

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

Favourable outcome of patients with breast cancer brain metastases treated with dual HER2 blockade of trastuzumab and pertuzumab. [2022]

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

A Retrospective Study on the Efficacy of Trastuzumab in HER2-Positive and Tamoxifen-Refractory Breast Cancer with Brain Metastasis. [2016]

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

HER2-positive breast cancer brain metastases: multiple responses to systemic chemotherapy and trastuzumab--a case report. [2018]