Atezolizumab + Trastuzumab Emtansine for Breast Cancer

(Astefania Trial)

Recruiting at 403 trial locations

Overseen By Reference Study ID Number: WO42633 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Hoffmann-La Roche

Must be taking: Taxane, Trastuzumab

Must not be taking: Immune checkpoint inhibitors

Disqualifiers: Stage IV cancer, 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

Compensation: Varies

Number of Visits: 14

Duration: 42 weeks

1188 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a Phase III, two-arm, randomized, double-blind placebo-controlled study in participants with HER2-positive primary breast cancer who have received preoperative chemotherapy and HER2-directed therapy, including trastuzumab followed by surgery, with a finding of residual invasive disease in the breast and/or axillary lymph nodes. As of June 4, 2024, this study is no longer accepting any newly screened participants.

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

The trial protocol does not specify if you need to stop your current medications. However, if you are on immunostimulatory or immunosuppressive agents, you may need to stop them, as these are part of the exclusion criteria.

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, if you are on immunostimulatory or immunosuppressive agents, you may need to stop them as they are part of the exclusion criteria.

What data supports the idea that Atezolizumab + Trastuzumab Emtansine for Breast Cancer is an effective drug?

The available research shows that Trastuzumab Emtansine (T-DM1) is effective for treating HER2-positive metastatic breast cancer. It has demonstrated better results and fewer side effects compared to standard treatments in several studies. For example, in the EMILIA trial, T-DM1 showed significant improvements in safety and effectiveness compared to a combination of other drugs, capecitabine and lapatinib. This suggests that T-DM1 is a strong option for patients who have already tried other treatments. ^{1 2 3 4 5}

What data supports the effectiveness of the drug trastuzumab emtansine (T-DM1) for breast cancer?

Trastuzumab emtansine (T-DM1) has shown effectiveness in treating HER2-positive metastatic breast cancer, demonstrating superior results compared to standard treatments in several studies, including phase II and III trials. It combines targeted therapy with a powerful cancer-fighting agent, offering improved outcomes for patients who have already received other HER2-directed therapies. ^{1 2 3 4 5}

What safety data is available for the treatment of Atezolizumab + Trastuzumab Emtansine for breast cancer?

The safety profile of Trastuzumab Emtansine (T-DM1) has been extensively studied in various trials and analyses. The EMILIA trial highlighted differences in safety between T-DM1 and capecitabine plus lapatinib, focusing on adverse events like grade ≥ 3 and grade 2 events. T-DM1 has shown improved tolerability compared to standard treatments in phase I, II, and III studies. However, there are reports of serious adverse events, such as a case of fatal acute eosinophilic pneumonia. A pharmacovigilance study identified common adverse events for T-DM1, including decreased platelet count and hepatopulmonary syndrome, with a higher incidence of fatal outcomes in the hepatobiliary system. Advanced age and male gender are risk factors for fatal adverse events. Overall, T-DM1 is associated with hematological, hepatobiliary, and nervous system toxicities, among others. ^{1 4 6 7 8}

Is the combination of Atezolizumab and Trastuzumab Emtansine safe for humans?

Trastuzumab emtansine (T-DM1) has been studied for safety in patients with HER2-positive breast cancer, showing some risks like decreased platelet count and liver-related issues. There have been reports of serious lung problems and liver toxicity, and older age and certain drug combinations may increase the risk of severe side effects. ^{1 4 6 7 8}

Is the drug Trastuzumab Emtansine a promising treatment for breast cancer?

Yes, Trastuzumab Emtansine is a promising drug for breast cancer. It combines the cancer-fighting abilities of trastuzumab with a powerful agent called DM1, showing better results and being easier to tolerate than standard treatments for HER2-positive breast cancer. ^{1 3 5 9 10}

What makes the drug Atezolizumab + Trastuzumab Emtansine unique for breast cancer?

Atezolizumab + Trastuzumab Emtansine is unique because it combines the targeted action of trastuzumab, which specifically attacks HER2-positive cancer cells, with the powerful cancer-killing agent DM1, delivered directly to the cancer cells. This combination offers improved effectiveness and tolerability compared to standard treatments for HER2-positive metastatic breast cancer. ^{1 3 5 9 10}

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

This trial is for individuals with HER2-positive breast cancer who've had preoperative chemotherapy and surgery but still have invasive disease. They should be in good health, with a life expectancy of at least 6 months, and must not have stage IV cancer or a history of certain other cancers within the last 5 years.

Inclusion Criteria

I've completed chemotherapy including treatments with taxane and trastuzumab.

It has been less than 12 weeks since my primary surgery.

You are expected to live for at least 6 more months.

Exclusion Criteria

I have an active liver disease.

You have a history of autoimmune disease or weak immune system.

I have moderate to severe numbness, tingling, or pain in my hands or feet.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive an IV infusion of atezolizumab or placebo prior to trastuzumab emtansine on Day 1 of each 21-day cycle for a total of 14 cycles

42 weeks

14 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

Long-term follow-up

Participants are monitored for invasive disease-free survival and quality of life

10 years

Treatment Details

Interventions

• Atezolizumab
• Placebo
• Trastuzumab
• Trastuzumab Emtansine

Trial Overview The study tests if Atezolizumab (an immunotherapy drug) or placebo, combined with Trastuzumab Emtansine (a targeted therapy), can prevent cancer recurrence in patients post-surgery. Participants are randomly assigned to one of two groups and treatment efficacy and safety are compared.

Participant Groups

Group I: Arm B: Atezolizumab + Trastuzumab Emtansine Experimental Treatment 3 Interventions

Participants will receive an IV infusion of atezolizumab prior to the IV infusion of trastuzumab emtansine on Day 1 of each 21-day cycle for a total of 14 cycles.

Group II: Arm A: Placebo + Trastuzumab Emtansine Active Control 3 Interventions

Participants will receive an intravenous (IV) infusion of placebo prior to the IV infusion of trastuzumab emtansine on Day 1 of each 21-day cycle for a total of 14 cycles.

Trastuzumab is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Herceptin for:

• Early breast cancer
• Metastatic breast cancer
• Advanced gastric cancer

Approved in United States as Herceptin for:

• Adjuvant treatment of HER2-positive breast cancer
• Metastatic breast cancer
• Advanced gastric cancer

Approved in Canada as Herceptin for:

• Early breast cancer
• Metastatic breast cancer
• Advanced gastric cancer

Approved in Japan as Herceptin for:

• Breast cancer
• Gastric cancer

Who Is Running the Clinical Trial?

Hoffmann-La Roche

Lead 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

Findings from Research

Trastuzumab emtansine (T-DM1) has shown a favorable safety profile in 884 patients with HER2-positive metastatic breast cancer, with most adverse events being manageable and asymptomatic, such as fatigue and nausea.

The treatment demonstrated superior efficacy compared to standard therapies in previous studies, making T-DM1 a promising option for further exploration in other breast cancer settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab emtansine in human epidermal growth factor receptor 2-positive metastatic breast cancer: an integrated safety analysis. Diéras, V., Harbeck, N., Budd, GT., et al.[2019]

In a study of 110 patients with HER2-positive metastatic breast cancer who had previously received multiple treatments, the antibody-drug conjugate trastuzumab emtansine (T-DM1) showed an overall response rate of 34.5% and a clinical benefit rate of 48.2%, indicating its effectiveness as a treatment option.

T-DM1 was well tolerated, with most side effects being mild (grades 1 to 2), and the most common severe side effects included thrombocytopenia and fatigue, suggesting a favorable safety profile for patients who have exhausted other HER2-targeted therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of trastuzumab emtansine in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer who were previously treated with trastuzumab, lapatinib, an anthracycline, a taxane, and capecitabine. Krop, IE., LoRusso, P., Miller, KD., et al.[2022]

Trastuzumab emtansine (T-DM1) is an effective treatment for advanced HER2-positive breast cancer, showing improved progression-free survival compared to traditional therapies like trastuzumab and docetaxel in clinical trials.

The Phase III EMILIA study demonstrated that T-DM1 provides a significant overall survival benefit over the combination of lapatinib and capecitabine, highlighting its potential as a personalized therapy that selectively delivers potent cytotoxic agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab emtansine in breast cancer. Dirix, LY., Rutten, A., Huget, P., et al.[2019]

In the phase III EMILIA trial, trastuzumab emtansine (T-DM1) demonstrated a significantly better safety profile compared to capecitabine plus lapatinib (CAP + LAP) in treating HER2-positive metastatic breast cancer, leading to fewer severe treatment-related adverse events.

The management of adverse events resulted in lower costs for T-DM1 (CAD 3380) compared to CAP + LAP (CAD 6901), indicating that T-DM1 not only provides effective treatment but also offers substantial savings to the Canadian public health-care system.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Profile and Costs of Related Adverse Events of Trastuzumab Emtansine for the Treatment of HER2-Positive Locally Advanced or Metastatic Breast Cancer Compared to Capecitabine Plus Lapatinib from the Perspective of the Canadian Health-Care System. Piwko, C., Prady, C., Yunger, S., et al.[2019]

In a study of 325 HER2-positive metastatic breast cancer patients, the objective response rate (ORR) for treatments following trastuzumab emtansine (T-DM1) was 22.8%, indicating limited effectiveness of post-T-DM1 therapies.

The median overall survival (OS) for patients after T-DM1 was 23.7 months, suggesting that while some patients may benefit, there is a need for further research into more effective treatment options beyond T-DM1.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical benefit of treatment after trastuzumab emtansine for HER2-positive metastatic breast cancer: a real-world multi-centre cohort study in Japan (WJOG12519B). Yokoe, T., Kurozumi, S., Nozawa, K., et al.[2021]

In a study of 232 Japanese patients with HER2-positive advanced breast cancer, trastuzumab emtansine (T-DM1) was found to be well tolerated, with 98.3% of patients experiencing adverse events but only 2.2% discontinuing treatment due to these events.

The most common serious adverse effects included thrombocytopenia in 29.7% of patients and hepatotoxicity in 11.2%, but no new safety concerns were identified, indicating that T-DM1 is a viable treatment option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Evaluation of Trastuzumab Emtansine in Japanese Patients with HER2-Positive Advanced Breast Cancer. Watanabe, J., Ito, Y., Saeki, T., et al.[2022]

In a comparison of the safety profiles of trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-DXd) using data from 3723 and 2045 adverse event reports respectively, T-DXd was associated with higher rates of fatal outcomes in the hematologic and respiratory systems, while T-DM1 had more severe outcomes in the hepatobiliary system.

Both drugs showed distinct adverse event patterns, with T-DM1 linked to nervous and musculoskeletal issues, and T-DXd associated with respiratory and gastrointestinal problems, highlighting the need for careful monitoring of specific risks in patients, especially those over 65 or on certain drug combinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Event Profile Differences between Trastuzumab Emtansine and Trastuzumab Deruxtecan: A Real-world, Pharmacovigilance Study. Liu, F., Yin, G., Xue, S., et al.[2023]

Ado-trastuzumab emtansine (T-DM1) is effective for treating HER2-positive breast cancers, but this case report highlights a serious risk of fatal pulmonary toxicity, specifically acute eosinophilic pneumonia, associated with its use.

The patient had previously received two HER2-targeted therapies, suggesting that prior treatments may contribute to the risk of additive toxicity when using T-DM1, indicating the need for careful monitoring in patients undergoing multiple lines of HER2-targeted therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute eosinophilic pneumonia: a fatal reaction to ado-trastuzumab. LaMorte, D., Desmond, D., Ellis, J., et al.[2023]

Trastuzumab emtansine (T-DM1) can cause lacrimal drainage system stenosis, leading to excessive tearing in patients, as seen in a case study of a 36-year-old woman with metastatic breast cancer.

The condition was successfully treated with a topical steroid (dexamethasone), demonstrating that while T-DM1 is effective for HER2-positive breast cancer, it can have side effects that are manageable with appropriate treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lacrimal drainage system stenosis associated with Trastuzumab emtansine (Kadcyla®, T-DM1) administration: a case report. Kim, CY., Kim, N., Choung, HK., et al.[2020]

In a study of 991 patients with HER2-positive advanced breast cancer, T-DM1 significantly improved progression-free survival (9.6 months) compared to lapatinib plus capecitabine (6.4 months), indicating its efficacy as a treatment option.

T-DM1 also demonstrated a better safety profile, with lower rates of severe adverse events (41% for T-DM1 vs. 57% for lapatinib plus capecitabine), making it a safer alternative for patients previously treated with trastuzumab and a taxane.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab emtansine for HER2-positive advanced breast cancer. Verma, S., Miles, D., Gianni, L., et al.[2022]

References

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

Trastuzumab emtansine in human epidermal growth factor receptor 2-positive metastatic breast cancer: an integrated safety analysis. [2019]

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

A phase II study of trastuzumab emtansine in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer who were previously treated with trastuzumab, lapatinib, an anthracycline, a taxane, and capecitabine. [2022]

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

Trastuzumab emtansine in breast cancer. [2019]

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

Safety Profile and Costs of Related Adverse Events of Trastuzumab Emtansine for the Treatment of HER2-Positive Locally Advanced or Metastatic Breast Cancer Compared to Capecitabine Plus Lapatinib from the Perspective of the Canadian Health-Care System. [2019]

5. Japan pubmed.ncbi.nlm.nih.gov

Clinical benefit of treatment after trastuzumab emtansine for HER2-positive metastatic breast cancer: a real-world multi-centre cohort study in Japan (WJOG12519B). [2021]

6. Greece pubmed.ncbi.nlm.nih.gov

Safety Evaluation of Trastuzumab Emtansine in Japanese Patients with HER2-Positive Advanced Breast Cancer. [2022]

7. Australia pubmed.ncbi.nlm.nih.gov

Adverse Event Profile Differences between Trastuzumab Emtansine and Trastuzumab Deruxtecan: A Real-world, Pharmacovigilance Study. [2023]

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

Acute eosinophilic pneumonia: a fatal reaction to ado-trastuzumab. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Lacrimal drainage system stenosis associated with Trastuzumab emtansine (Kadcyla®, T-DM1) administration: a case report. [2020]

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

Trastuzumab emtansine for HER2-positive advanced breast cancer. [2022]