Atezolizumab + Chemotherapy for HER2-Positive Breast Cancer

Overseen By Lori J Goldstein, MD

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Fox Chase Cancer Center

Must not be taking: Steroids, Immunosuppressants, Anti-TNF agents

Disqualifiers: CNS metastases, Autoimmune disease, HIV, 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: 9

Duration: 18 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for women with HER2-positive breast cancer that has spread or cannot be surgically removed. Researchers aim to determine if adding atezolizumab, an immunotherapy drug, to a standard chemotherapy regimen can safely and effectively combat the cancer. Women with confirmed HER2-positive breast cancer that is advanced or metastatic, and who have measurable disease, might be suitable for this study. Participants will receive a combination of drugs, including atezolizumab, paclitaxel, trastuzumab, and pertuzumab. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in cancer therapy.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, including systemic corticosteroids, immunosuppressive medications, and herbal medications. If you are using a RANKL inhibitor like denosumab, it must be discontinued during the study. Bisphosphonate therapy is allowed.

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

Research has shown that the treatments in this trial have been tested for safety in people before. Atezolizumab, when combined with other treatments for HER2-positive breast cancer, is generally safe. Studies found that combining atezolizumab with chemotherapy is both effective and safe for patients with this type of breast cancer.

Paclitaxel has also been well-researched and is considered safe for treating breast cancer. Recent studies show it works well and is safe at all stages of the disease.

Pertuzumab is safe when used with other medications for HER2-positive breast cancer. Research has shown it helps slow down cancer growth while being safe for patients.

Trastuzumab is another treatment with a strong safety record. It has been widely studied and is known to lower the risk of cancer recurrence in people with HER2-positive breast cancer.

Overall, these drugs have a history of being well-tolerated by patients with this type of cancer. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for breast cancer?

Researchers are excited about this treatment for HER2-positive breast cancer because it combines atezolizumab with established chemotherapy agents like paclitaxel, pertuzumab, and trastuzumab in a novel way. Atezolizumab is an immune checkpoint inhibitor that works by unleashing the immune system to target cancer cells more effectively, which is different from the traditional chemotherapy approaches. This combination aims to enhance the immune response while directly attacking cancer cells, potentially leading to better outcomes and fewer recurrences. By integrating this immune-boosting drug with chemotherapy, the treatment could offer a more comprehensive attack on the cancer, possibly improving survival rates and quality of life for patients.

What evidence suggests that this treatment might be an effective treatment for HER2-positive breast cancer?

Research has shown that combining atezolizumab with treatments like trastuzumab and pertuzumab has promising effects on HER2-positive breast cancer. In this trial, participants will receive a combination of these treatments. Studies have found that about 60.3% of patients receiving similar combinations showed no signs of cancer in their tissue samples after treatment. Paclitaxel, often used with trastuzumab, has been associated with a 98.7% chance of being disease-free three years post-treatment. Adding pertuzumab to treatment plans significantly improved survival rates. Trastuzumab is well-known for reducing the chance of cancer recurrence and improving overall survival in HER2-positive breast cancer cases. Together, these findings suggest that using these treatments in combination can effectively combat this type of breast cancer. ^{1 4 6 7 8}

Are You a Good Fit for This Trial?

This trial is for women over 18 with HER2-positive breast cancer that's advanced and can't be removed by surgery. They must have good organ function, not be pregnant or breastfeeding, agree to use contraception, and not have had certain treatments or conditions that could interfere with the study.

Inclusion Criteria

I am a woman with HER2-positive breast cancer that cannot be surgically removed or has spread.

My cancer is HER2 positive based on specific tests.

I have at least one tumor that can be measured on a CT scan.

Exclusion Criteria

My tumor cannot be measured or monitored with current methods.

Patients with known prior hypersensitivity reaction to any of the study drugs

You have HIV.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive atezolizumab in combination with paclitaxel, trastuzumab, and pertuzumab

18 weeks

Weekly visits for paclitaxel administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Tumor measurements and bone scans every 9 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Atezolizumab
• Paclitaxel
• Pertuzumab
• Trastuzumab

Trial Overview The trial tests atezolizumab combined with paclitaxel, trastuzumab, and pertuzumab in patients with metastatic HER-2 positive breast cancer. It aims to see how safe this combination is and how well it works without long-term corticosteroid use.

How Is the Trial Designed?

Group I: Investigational Arm Experimental Treatment 4 Interventions

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?

Fox Chase Cancer Center

Lead Sponsor

Trials

236

Recruited

39,300+

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

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 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 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]

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]

Combining anti-HER2 monoclonal antibodies like trastuzumab and pertuzumab with radiation therapy appears to be safe, showing no significant increase in toxicity based on the reviewed literature.

However, caution is advised when combining radiation with tyrosine kinase inhibitors (like lapatinib and tucatinib) and certain antibody-drug conjugates, as the safety of these combinations is not well established.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interaction between Radiation Therapy and Targeted Therapies in HER2-Positive Breast Cancer: Literature Review, Levels of Evidence for Safety and Recommendations for Optimal Treatment Sequence. Debbi, K., Grellier, N., Loganadane, G., et al.[2023]

In a study involving 397 patients with HER2-positive early breast cancer, treatment with pertuzumab and trastuzumab alongside anthracycline-containing regimens showed a low incidence of serious cardiac events, with only 1.5% experiencing class III/IV heart failure and 6.5% having declines in left ventricular ejection fraction in one treatment cohort.

The pathologic complete response (pCR) rates were high, at 61.8% and 60.7% for the two treatment cohorts, indicating that this combination therapy is both effective and maintains a favorable safety profile, consistent with previous studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pertuzumab, trastuzumab, and standard anthracycline- and taxane-based chemotherapy for the neoadjuvant treatment of patients with HER2-positive localized breast cancer (BERENICE): a phase II, open-label, multicenter, multinational cardiac safety study. Swain, SM., Ewer, MS., Viale, G., et al.[2022]

In a phase 3 trial involving 780 patients with HER2-positive metastatic gastric or gastro-oesophageal junction cancer, adding pertuzumab to trastuzumab and chemotherapy did not significantly improve overall survival compared to placebo, with median survival times of 17.5 months for the pertuzumab group and 14.2 months for the control group.

While serious adverse events were more common in the pertuzumab group (45%) compared to the control group (39%), no treatment-related deaths occurred in the pertuzumab group, suggesting a safety profile that warrants further investigation despite the lack of survival benefit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pertuzumab plus trastuzumab and chemotherapy for HER2-positive metastatic gastric or gastro-oesophageal junction cancer (JACOB): final analysis of a double-blind, randomised, placebo-controlled phase 3 study. Tabernero, J., Hoff, PM., Shen, L., et al.[2023]

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. 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, ...

4. 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.

5. aacrjournals.org aacrjournals.org/clincancerres/article/30/21/4856/749139/A-Phase-II-Study-of-Atezolizumab-Pertuzumab-and

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 HER2-positive ...

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 ...

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

A Phase II Study of Atezolizumab, Pertuzumab, and High- ... This was a single-arm, multicenter, phase II trial of atezolizumab, pertuzumab, and high-dose trastuzumab for patients with HER2-positive breast cancer brain ...