Chemotherapy + Atezolizumab for Breast Cancer

Recruiting at 216 trial locations

Overseen By Director, Department of Site and Study Management

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: NSABP Foundation Inc

Must not be taking: Anthracyclines, Taxanes, Immunosuppressants, others

Disqualifiers: Metastatic disease, Cardiac disease, Autoimmune, others

Stay on Your Current Meds You can continue your current medications while participating

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: 7

1550 Participants Needed

Trial Summary

What is the purpose of this trial?

The main purpose of this study is to learn if the usual chemotherapy given before surgery (neoadjuvant therapy) for breast cancer plus the experimental drug, atezolizumab, is better than the usual chemotherapy plus a placebo. (A placebo is a drug that looks like the study drug but contains no medication.) The usual chemotherapy in this study is paclitaxel (WP) and carboplatin followed by doxorubicin and cyclophosphamide (AC) or epirubicin and cyclophosphamide (EC). Usually, after neoadjuvant therapy and surgery for triple negative breast cancer, no additional treatment is given unless the cancer returns. This study will also look at continuing treatment after surgery with atezolizumab or the placebo. To be better, atezolizumab given with the neoadjuvant therapy should be better at: 1) decreasing the amount of tumor in the breast than the placebo given with the usual chemotherapy and 2) decreasing the chance of the cancer from returning after surgery. Another purpose of this study is to test the good and bad effects of atezolizumab when added to the usual chemotherapy. Atezolizumab may keep your cancer from growing but it can also cause side effects.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications. However, it does exclude those on certain treatments like systemic immunosuppressive medications and therapeutic anti-coagulants. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug Atezolizumab for breast cancer?

Research shows that Atezolizumab, when combined with chemotherapy, has been effective in treating advanced triple-negative breast cancer (TNBC), as it significantly prolonged the time patients lived without the disease getting worse. This combination was approved based on the IMpassion130 trial, which demonstrated its benefits for patients with PD-L1-positive TNBC. ^{1 2 3 4 5}

Is the combination of chemotherapy and atezolizumab safe for treating breast cancer?

The combination of atezolizumab (Tecentriq) and chemotherapy has been studied for safety in treating advanced triple-negative breast cancer. Common side effects include low white blood cell counts, nerve damage, and immune-related issues like skin rash, thyroid problems, and liver inflammation. Overall, the safety profile is consistent with known effects of each drug individually. ^{1 3 6 7 8}

How is the drug Atezolizumab unique in treating breast cancer?

Atezolizumab is unique because it is the first immunotherapy drug approved for treating advanced triple-negative breast cancer (TNBC) when combined with chemotherapy. It works by targeting PD-L1, a protein that helps cancer cells evade the immune system, making it a novel option for this hard-to-treat cancer type. ^{1 2 3 5 7}

Research Team

Norman Wolmark, MD

Principal Investigator

NSBP Foundation, Inc.

Eligibility Criteria

This trial is for adults with triple-negative breast cancer who haven't had certain treatments yet. They should be relatively healthy, able to perform daily activities (ECOG 0-1), and have normal organ function. Women must not be pregnant or breastfeeding and agree to contraception if of childbearing potential.

Inclusion Criteria

You have agreed to take part in the study and have signed a form that explains the study and how your information will be used. This includes giving a sample of your tumor for research purposes.

I am fully active or can carry out light work.

The patient must have consented to participate and signed an appropriate IRB-approved consent form

Exclusion Criteria

I have had breast cancer in the opposite breast before.

You have had a transplant using cells or organs from another person.

My high blood pressure is not under control.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Chemotherapy

Participants receive neoadjuvant chemotherapy with atezolizumab or placebo, including paclitaxel and carboplatin followed by AC/EC

12 weeks

Weekly visits for paclitaxel and every 3 weeks for carboplatin

Surgery

Participants undergo surgery to remove the tumor

1 week

1 visit for surgery

Adjuvant Therapy

Participants receive adjuvant therapy with atezolizumab or placebo for approximately 6 months, potentially with concurrent radiation therapy

24 weeks

Every 3 weeks for IV infusion

Follow-up

Participants are monitored for safety and effectiveness after treatment

22 months

Treatment Details

Interventions

• Atezolizumab
• Placebo

Trial Overview The study tests whether adding Atezolizumab to standard pre-surgery chemotherapy is more effective than chemo with a placebo in shrinking tumors and preventing cancer return post-surgery. After surgery, patients may continue receiving Atezolizumab or placebo to further assess benefits.

Participant Groups

Group I: Atezolizumab Experimental Treatment 1 Intervention

IV infusion, 1200mg, once every 3 weeks for 4 doses (Cycle 1), once every 3 weeks for 4 doses (Cycle 2) and once every 3 weeks after surgery for 1 year after first dose

Group II: Placebo Placebo Group 1 Intervention

IV infusion once every 3 weeks for 4 doses (Cycle 1), once every 3 weeks for 4 doses (Cycle 2) and once every 3 weeks after surgery for 1 year after first dose

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?

NSABP Foundation Inc

Lead Sponsor

Trials

89

Recruited

140,000+

Hoffmann-La Roche

Industry Sponsor

Trials

2,482

Recruited

1,107,000+

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Avastin, Herceptin, Rituxan, Accu-Chek

Dr. Levi Garraway

Hoffmann-La Roche

Chief Medical Officer since 2019

MD from the University of Basel

Dr. Thomas Schinecker

Hoffmann-La Roche

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

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

Atezolizumab, combined with nab-paclitaxel, significantly improved progression-free survival in patients with advanced triple-negative breast cancer (TNBC) compared to placebo, based on the phase III IMpassion130 trial involving patients with unresectable locally advanced or metastatic TNBC.

While the combination therapy showed a tolerable safety profile, with common side effects like neutropenia and immune-related adverse events, it did not significantly affect health-related quality of life for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab (in Combination with Nab-Paclitaxel): A Review in Advanced Triple-Negative Breast Cancer. Kang, C., Syed, YY.[2020]

The ASTEFANIA trial is designed to assess the effectiveness of combining atezolizumab, an immunotherapy, with ado-trastuzumab emtansine in treating high-risk, HER2-positive early breast cancer patients who have residual disease after initial HER2-targeted therapy.

This study will involve 1700 participants across 32 countries, focusing on invasive disease-free survival as the primary outcome, while also evaluating safety and pharmacokinetics, highlighting the potential for enhanced treatment strategies in early-stage breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ASTEFANIA: adjuvant ado-trastuzumab emtansine and atezolizumab for high-risk, HER2-positive breast cancer. Hurvitz, SA., Bachelot, T., Bianchini, G., et al.[2022]

Atezolizumab, the first anti-PD-L1 monoclonal antibody approved by the FDA, has shown promising efficacy in treating metastatic triple-negative breast cancer, supported by data from the Phase III IMpassion130 trial.

The review highlights the pharmacodynamic and pharmacokinetic properties of atezolizumab, emphasizing its safety and effectiveness in various cancers, including small-cell lung cancer and renal cell cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab for use in PD-L1-positive unresectable, locally advanced or metastatic triple-negative breast cancer. Mavratzas, A., Seitz, J., Smetanay, K., et al.[2020]

Atezolizumab is a monoclonal antibody that targets PD-L1, which is being developed for treating various blood cancers and solid tumors, showing promise in cancer immunotherapy.

It has already been approved in the US as a second-line treatment for urothelial carcinoma and is pending approval for non-small cell lung cancer, highlighting its potential efficacy in these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: First Global Approval. Markham, A.[2019]

Atezolizumab, combined with nab-paclitaxel, significantly improves progression-free survival and overall survival in patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC), as demonstrated in the IMpassion 130 trial.

The FDA and EMA approvals of atezolizumab represent a major advancement in treating metastatic TNBC, but further research is needed to identify better biomarkers for response and strategies to enhance treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab for the treatment of breast cancer. Reddy, SM., Carroll, E., Nanda, R.[2021]

References

1. Bosnia and Herzegovina pubmed.ncbi.nlm.nih.gov

Targeted immunotherapy with a checkpoint inhibitor in combination with chemotherapy: A new clinical paradigm in the treatment of triple-negative breast cancer. [2020]

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

Patient-reported outcomes from a randomized trial of neoadjuvant atezolizumab-chemotherapy in early triple-negative breast cancer. [2022]

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

Atezolizumab (in Combination with Nab-Paclitaxel): A Review in Advanced Triple-Negative Breast Cancer. [2020]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Emerging combination immunotherapy strategies for breast cancer: dual immune checkpoint modulation, antibody-drug conjugates and bispecific antibodies. [2022]

5. England pubmed.ncbi.nlm.nih.gov

ASTEFANIA: adjuvant ado-trastuzumab emtansine and atezolizumab for high-risk, HER2-positive breast cancer. [2022]

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

Atezolizumab for use in PD-L1-positive unresectable, locally advanced or metastatic triple-negative breast cancer. [2020]

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

Atezolizumab: First Global Approval. [2019]

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

Atezolizumab for the treatment of breast cancer. [2021]