Atezolizumab + Standard Therapy for HER2-Positive Breast Cancer

Not currently recruiting at 753 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of a combination of treatments, including atezolizumab (Tecentriq, an immunotherapy drug), for individuals with HER2-positive breast cancer that has metastasized. The treatments being tested function in various ways: some inhibit cancer cell growth, others mark them for immune system destruction, and atezolizumab may enhance the body's immune response against the cancer. Participants will receive a combination of these treatments to assess whether adding atezolizumab increases their effectiveness. The trial seeks individuals diagnosed with HER2-positive breast cancer that is either locally advanced or metastatic, with measurable disease outside the central nervous system. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants an opportunity to contribute to potentially groundbreaking treatment advancements.

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.

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

Research has shown that atezolizumab, when combined with other treatments for HER2-positive breast cancer, is generally safe for patients. One study found that adding atezolizumab to drugs like trastuzumab and pertuzumab was effective and well-tolerated. Another study examined its use in various types of breast cancer and found no unexpected safety issues.

For the other treatments in this study—paclitaxel, trastuzumab, and pertuzumab—extensive safety information exists, as they are commonly used for breast cancer. These treatments are generally well-tolerated, though they can have side effects like all medications.

Since this trial is in a later stage, earlier studies have already demonstrated these treatments to be safe enough for larger groups of people, which is a positive indicator for their safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about atezolizumab in combination with standard therapy for HER2-positive breast cancer because it offers a novel approach by harnessing the body's immune system to fight cancer. While standard treatments like pertuzumab, trastuzumab, and taxane therapies focus on targeting HER2 receptors on cancer cells, atezolizumab is an immune checkpoint inhibitor that blocks the PD-L1 protein, potentially enhancing the immune response against cancer cells. This dual-action strategy could offer improved outcomes by not only targeting cancer cells directly but also boosting the body's natural defenses. By integrating immunotherapy with established cancer treatments, researchers hope to achieve more effective and durable responses in patients.

What evidence suggests that this trial's treatments could be effective for metastatic breast cancer?

Research has shown that adding atezolizumab to standard treatments for HER2-positive breast cancer looks promising. In this trial, participants in one arm will receive atezolizumab combined with trastuzumab, pertuzumab, and taxane therapy. Some studies have reported a high rate of complete response with this combination, meaning no signs of cancer remain. For instance, one study found a 60.3% complete response rate in early-stage HER2-positive breast cancer when atezolizumab was included. This suggests that atezolizumab might help boost the body's immune system to fight cancer cells. However, more information is needed to confirm its effectiveness in advanced cancer cases. The standard drugs, trastuzumab and pertuzumab, are already known to effectively target and block growth signals in cancer cells. ^{1 4 5 6 7}

Who Is on the Research Team?

Charles E Geyer

Principal Investigator

NRG Oncology

Are You a Good Fit for This Trial?

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.

I am HIV positive, on treatment, and my viral load is undetectable.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9426828/

Primary Results of the Randomized Phase III IMpassion050 Trial Atezolizumab with neoadjuvant dose-dense doxorubicin/cyclophosphamide–paclitaxel and PH for high-risk, HER2-positive early breast cancer did not increase pCR ...

2. nature.com nature.com/articles/s43018-024-00890-2

the randomized phase 2 ABCSG-52/ATHENE trial The residual cancer burden 0/I rate and objective response rate (secondary endpoints) in all patients with evaluable data were 80.0% (n = 44/55; ...

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

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

4. cancernetwork.com cancernetwork.com/view/neoadjuvant-atezolizumab-combo-yields-high-pcr-rates-in-her2-breast-cancer

Neoadjuvant Atezolizumab Combo Yields High pCR ... The pCR rate was 60.3% (n = 35/58; 95% CI, 47.5%-71.9%) across the intent-to-treat population, which included rates of 65.5% (n = 19/29; 95% CI, ...

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. clinicaltrials.gov clinicaltrials.gov/study/NCT02605915

Study Details | NCT02605915 | Safety and ... Safety and Pharmacokinetics of Atezolizumab Combination Treatments in Participants With HER2-Positive and HER2-Negative Breast Cancer. ClinicalTrials.gov ID ...

7. aacrjournals.org aacrjournals.org/cancerres/article/83/5_Supplement/OT2-16-05/717519/Abstract-OT2-16-05-Safety-Analyses-of-NRG-BR004-A

Abstract OT2-16-05: Safety Analyses of NRG BR004: A ... NRG BR004 was a phase III, placebo-controlled trial designed to determine whether the addition of the PD-L1 inhibitor, atezolizumab, to THP would improve ...