Atezolizumab + Standard Therapy for HER2-Positive Breast Cancer

Recruiting at 739 trial locations

Overseen By Leon C. Hwang

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: National Cancer Institute (NCI)

Must be taking: Trastuzumab, Pertuzumab, Taxane

Must not be taking: mTOR inhibitors, CDK 4/6 inhibitors

Disqualifiers: Uncontrolled hypertension, Cardiac disease, Autoimmune disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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: 9

Duration: 2 years

190 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, certain medications, especially those that are immunosuppressive or immunomodulatory, may need to be stopped before joining the study. It's best to discuss your current medications with the study team to get specific guidance.

What data supports the effectiveness of the drug Atezolizumab combined with standard therapy for HER2-positive breast cancer?

Research shows that combining Atezolizumab with standard treatments like trastuzumab and pertuzumab may enhance the body's immune response against cancer and improve outcomes in HER2-positive breast cancer. Specifically, the IMpassion050 trial suggests that this combination can boost antitumor activity in early-stage HER2-positive breast cancer. ^{1 2 3 4 5}

Is the combination of Atezolizumab and standard therapy safe for HER2-positive breast cancer?

The combination of trastuzumab and pertuzumab, which are part of the standard therapy for HER2-positive breast cancer, has been shown to be generally safe, although cardiac safety data is limited. Paclitaxel, another component, is commonly used and its safety profile is well-established in combination with these drugs. ^{2 6 7 8 9}

How is the drug Atezolizumab + Standard Therapy unique for treating HER2-positive breast cancer?

This treatment combines Atezolizumab, an immunotherapy drug that boosts the body's immune response against cancer, with standard HER2-targeted therapies (pertuzumab and trastuzumab) and chemotherapy (paclitaxel), potentially enhancing the overall anticancer effects and improving outcomes for patients with high-risk HER2-positive breast cancer. ^{1 2 3 10 11}

What is the purpose of this trial?

This randomized phase III trial studies how well paclitaxel, trastuzumab, and pertuzumab with or without atezolizumab works in treating patients with breast cancer that has spread to other parts of the body (metastatic). Chemotherapy drugs, such as paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Trastuzumab is a form of "targeted therapy" because it works by attaching itself to specific molecules (receptors) on the surface of cancer cells, known as HER2 receptors. When trastuzumab attaches to HER2 receptors, the signals that tell the cells to grow are blocked and the cancer cell may be marked for destruction by the body's immune system. Monoclonal antibodies, such as pertuzumab, may interfere with the ability of cancer cells to grow and spread. Immunotherapy with monoclonal antibodies, such as atezolizumab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. It is not yet known whether giving paclitaxel, trastuzumab, and pertuzumab with or without atezolizumab may kill more tumor cells. \*NOTE: This study has a central confirmation step. The purpose of this step is to confirm by central testing that the patient's tumor has specific receptors. If the patient meets all the study requirements, the patient will join the study and begin therapy for breast cancer while the tumor is being tested.

Research Team

Charles E Geyer

Principal Investigator

NRG Oncology

Eligibility Criteria

This trial is for adults with HER2-positive metastatic breast cancer. Eligible participants have a tumor no larger than 3 cm, four or fewer brain metastases, measurable disease, and proper organ function. HIV-positive patients can join if they're on effective therapy. Pregnant women, those planning pregnancy, or lactating are excluded.

Inclusion Criteria

I am fully active or can carry out light work.

My blood clotting tests are within the required range.

Patients must agree to use adequate contraception

Exclusion Criteria

I do not have brain metastases that meet exclusion criteria.

I have a history of specific health conditions related to cancer, heart, nervous system, allergies, skin, immune system, infections, or have had a transplant.

I have health issues that could make treatment risky or affect test results.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Central Confirmation

Central testing to confirm that the patient's tumor has specific receptors

2 weeks

Treatment

Patients receive pertuzumab, trastuzumab, and paclitaxel or docetaxel with or without atezolizumab. Cycles repeat every 6 weeks for up to 2 years.

2 years

Visits every 6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

8 years

Every 3 months for 3 years, then every 6 months for 5 years

Treatment Details

Interventions

• Atezolizumab
• Paclitaxel
• Pertuzumab
• Trastuzumab

Trial Overview The study tests how well the usual therapy (paclitaxel, trastuzumab, pertuzumab) works with or without atezolizumab in treating first-line HER2-positive metastatic breast cancer. It's a randomized phase III trial where some patients will also receive a placebo instead of atezolizumab.

Participant Groups

Group I: Arm I (pertuzumab, trastuzumab, taxane therapy, atezolizumab) Experimental Treatment 10 Interventions

Patients receive pertuzumab IV over 30-60 minutes on days 1 and 22, trastuzumab IV over 30-90 minutes on days 1 and 22, and paclitaxel IV over 60 minutes on days 1, 8, 15, 22, 29, and 36 or docetaxel IV over 60 minutes on days 1 and 22. Cycles repeat every 6 weeks in the absence of disease progression or unacceptable toxicity. Patients also receive atezolizumab IV over 30-60 minutes on day 22 of cycle 1 and days 1 and 22 of subsequent cycles. Cycles repeat every 6 weeks for 2 years in the absence of disease progression or unacceptable toxicity. Patients may undergo a biopsy at baseline. Patients undergo a CT or MRI at baseline, prior to weeks 10, 19, 28 and then at 9, 12, 15, 18, 21, and 24 months from study entry, every 3 months through year 3, every 6 months for years 4 and 5, and then every 6 months for years 6 through 10 from study entry. Patients undergo a bone scan at baseline, every 6 months from study entry, every 6 months through year 3, and every 12 months for years 4 and 5.

Group II: Arm II (pertuzumab, trastuzumab, taxane therapy, placebo) Active Control 10 Interventions

Patients receive pertuzumab, trastuzumab, and paclitaxel or docetaxel as in Arm I. Patients also receive placebo IV 30-60 minutes on day 1 of cycle 22 and days 1 and 22 of subsequent cycles. Cycles repeat every 6 weeks for 2 years in the absence of disease progression or unacceptable toxicity. Patients may undergo a biopsy at baseline. Patients undergo a CT or MRI at baseline, prior to weeks 10, 19, 28 and then at 9, 12, 15, 18, 21, and 24 months from study entry, every 3 months through year 3, every 6 months for years 4 and 5, and then every 6 months for years 6 through 10 from study entry. Patients undergo a bone scan at baseline every 6 months from study entry, every 6 months through year 3, and every 12 months for years 4 and 5.

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?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

NRG Oncology

Collaborator

Trials

242

Recruited

105,000+

Findings from Research

In a phase III trial involving patients with high-risk HER2-positive early breast cancer, the addition of atezolizumab to standard treatment (pertuzumab-trastuzumab and chemotherapy) did not significantly improve the rates of pathologic complete response (pCR) compared to placebo, with pCR rates being 62.7% for placebo and 62.4% for atezolizumab in the overall population.

While the safety profile of atezolizumab was consistent with previous studies, it was associated with a higher frequency of serious adverse events, including five grade 5 adverse events, indicating a need for careful consideration of its use in combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab With Neoadjuvant Anti-Human Epidermal Growth Factor Receptor 2 Therapy and Chemotherapy in Human Epidermal Growth Factor Receptor 2-Positive Early Breast Cancer: Primary Results of the Randomized Phase III IMpassion050 Trial. Huober, J., Barrios, CH., Niikura, N., et al.[2022]

In a study of 152 patients with HER2-positive metastatic breast cancer, the combination of taxanes with trastuzumab and pertuzumab showed a significant progression-free survival (PFS) advantage over vinorelbine in patients with newly diagnosed metastatic disease, indicating a potential benefit for this specific group.

Overall, there was no significant difference in overall survival (OS) between the two treatment groups, suggesting that both taxanes and vinorelbine are viable options when combined with trastuzumab and pertuzumab for first-line treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Taxane versus vinorelbine in combination with trastuzumab and pertuzumab for first-line treatment of metastatic HER2-positive breast cancer: a retrospective two-center study. Reinhorn, D., Kuchuk, I., Shochat, T., et al.[2021]

The combination of atezolizumab with trastuzumab emtansine did not significantly improve progression-free survival in patients with HER2-positive metastatic breast cancer compared to trastuzumab emtansine alone, with a median survival of 8.2 months versus 6.8 months, indicating no clinically meaningful benefit.

Patients receiving atezolizumab experienced a higher frequency of adverse events, including serious complications, suggesting that this combination therapy may pose additional risks without clear advantages in efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab emtansine plus atezolizumab versus trastuzumab emtansine plus placebo in previously treated, HER2-positive advanced breast cancer (KATE2): a phase 2, multicentre, randomised, double-blind trial. Emens, LA., Esteva, FJ., Beresford, M., et al.[2020]

In a study of 57 patients with HER2-positive breast cancer receiving neoadjuvant treatment with doxorubicin and cyclophosphamide followed by trastuzumab and pertuzumab, only 3.5% developed severe heart failure, indicating a relatively low cardiac event rate.

The study found no increased risk of cardiotoxicity from the combination of trastuzumab and pertuzumab after doxorubicin-based chemotherapy, suggesting that this treatment regimen is cardiac safe for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiac Safety of Dual Anti-HER2 Therapy in the Neoadjuvant Setting for Treatment of HER2-Positive Breast Cancer. Yu, AF., Singh, JC., Wang, R., et al.[2018]

Pertuzumab, a new monoclonal antibody targeting HER2, has shown improved patient outcomes in clinical trials for early-stage and metastatic HER2-positive breast cancer, especially when used in combination with chemotherapy and trastuzumab.

The review highlights that while trastuzumab has improved survival for HER2-positive breast cancer, there is still a need for better treatment options, which pertuzumab aims to address, particularly for patients who continue to relapse.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pertuzumab in human epidermal growth-factor receptor 2-positive breast cancer: clinical and economic considerations. Lamond, NW., Younis, T.[2021]

The combination of tucatinib, trastuzumab, and capecitabine has shown significant improvements in progression-free survival (PFS) and overall survival (OS) for patients with HER2-positive breast cancer who have previously received standard treatments, including those with brain metastases.

New therapies like neratinib and margetuximab also demonstrate longer PFS compared to traditional treatments, although improvements in overall survival have not yet been established, highlighting the ongoing need for effective options in later lines of therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metastatic Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: Current Treatment Standards and Future Perspectives. Dormann, C.[2022]

References

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

Atezolizumab With Neoadjuvant Anti-Human Epidermal Growth Factor Receptor 2 Therapy and Chemotherapy in Human Epidermal Growth Factor Receptor 2-Positive Early Breast Cancer: Primary Results of the Randomized Phase III IMpassion050 Trial. [2022]

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

Taxane versus vinorelbine in combination with trastuzumab and pertuzumab for first-line treatment of metastatic HER2-positive breast cancer: a retrospective two-center study. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Trastuzumab emtansine plus atezolizumab versus trastuzumab emtansine plus placebo in previously treated, HER2-positive advanced breast cancer (KATE2): a phase 2, multicentre, randomised, double-blind trial. [2020]

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

Efficacy and Safety of Gemcitabine With Trastuzumab and Pertuzumab After Prior Pertuzumab-Based Therapy Among Patients With Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer: A Phase 2 Clinical Trial. [2022]

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

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

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

Cardiac Safety of Dual Anti-HER2 Therapy in the Neoadjuvant Setting for Treatment of HER2-Positive Breast Cancer. [2018]

7. 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]

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

The expanding role of pertuzumab in the treatment of HER2-positive breast cancer. [2021]

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

Pertuzumab in human epidermal growth-factor receptor 2-positive breast cancer: clinical and economic considerations. [2021]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Metastatic Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: Current Treatment Standards and Future Perspectives. [2022]

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

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