Atezolizumab + Pertuzumab + Trastuzumab for Breast Cancer with Brain Metastases

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a combination of three drugs—atezolizumab (an immunotherapy drug), pertuzumab, and trastuzumab—can effectively treat HER2-positive breast cancer that has spread to the brain. The goal is to determine if these drugs can control or shrink brain tumors. Individuals with HER2-positive breast cancer and measurable brain tumors, who show noticeable progression of their brain metastases, 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.

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.

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

Research shows that the combination of atezolizumab, pertuzumab, and trastuzumab is generally safe for people. Studies have found that patients with HER2-positive breast cancer and brain metastases can use this drug combination without major problems.

The reviewed studies report no serious safety concerns for this treatment. However, like many cancer treatments, patients might experience side effects. These can range from mild to more noticeable, but the study data does not highlight any new or unexpected safety issues.

Both pertuzumab and trastuzumab are already approved for treating breast cancer, indicating their safety is well-established. Atezolizumab is also approved for other types of cancer, showing it has been tested for safety in humans before.

In summary, the combination treatment of atezolizumab, pertuzumab, and trastuzumab appears safe based on available studies, but participating in a clinical trial will provide more detailed information tailored to individual experiences. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of atezolizumab, pertuzumab, and trastuzumab for treating breast cancer with brain metastases because it brings together a unique trio of cancer-fighting agents. Unlike traditional treatments that might focus on a single target, this combo uses atezolizumab to boost the immune system's response against cancer cells, while pertuzumab and trastuzumab work together to block specific proteins that help cancer grow. This multi-faceted approach could potentially improve treatment effectiveness and offer hope for better outcomes in a condition that's notoriously challenging to treat.

What evidence suggests that this trial's treatments could be effective for HER2-positive metastatic breast cancer with brain metastases?

This trial will evaluate the combination of atezolizumab, pertuzumab, and trastuzumab for patients with HER2-positive breast cancer that has spread to the brain. Research has shown that this combination does not effectively treat brain issues in these patients. Several studies have found that adding atezolizumab to pertuzumab and trastuzumab does not improve outcomes for brain tumors. However, in other contexts, using atezolizumab with pertuzumab and trastuzumab has shown promise. For instance, in early-stage HER2-positive breast cancer, this combination, when used with epirubicin before surgery, resulted in a 60.3% complete response rate, indicating no signs of cancer. This suggests that while the combination is beneficial in some cases, it is not very effective for brain tumors. ^{1 2 3 4 6}

Who Is on the Research Team?

Nancy Lin

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11528201/

A Phase II Study of Atezolizumab, Pertuzumab, and High ... The addition of atezolizumab to pertuzumab plus high-dose trastuzumab does not result in improved CNS responses in patients with HER2-positive breast cancer ...

2. aacrjournals.org aacrjournals.org/clincancerres/article/doi/10.1158/1078-0432.CCR-24-1161/747761/am/A-phase-II-study-of-atezolizumab-pertuzumab-and

A phase II study of atezolizumab, pertuzumab, and high-dose ... Conclusions: The addition of atezolizumab to pertuzumab plus high-dose trastuzumab does not result in improved CNS responses in patients with HER2-positive ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03417544

Atezolizumab + Pertuzumab + Trastuzumab In CNS Mets In ... 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.

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39226397/

A Phase II Study of Atezolizumab, Pertuzumab, and High- ... The addition of atezolizumab to pertuzumab plus high-dose trastuzumab does not result in improved CNS responses in patients with ...

5. onclive.com onclive.com/view/neoadjuvant-atezolizumab-trastuzumab-pertuzumab-is-effective-and-safe-in-her2-early-breast-cancer

Neoadjuvant Atezolizumab/Trastuzumab/Pertuzumab Is ... Neoadjuvant atezolizumab with dual HER2 blockade and epirubicin achieved a 60.3% pCR rate in patients with early HER2-positive breast cancer.

6. sciencedirect.com sciencedirect.com/science/article/pii/S2666379124002672

Emerging treatments in HER2-positive advanced breast ... Notably, there was a strong trend toward improved PFS in patients with brain metastases. Variations on the theme “trastuzumab and pertuzumab” as ...