Atezolizumab + Trastuzumab Emtansine for Breast Cancer

(Astefania Trial)

Not currently recruiting at 486 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new combination treatment for individuals with HER2-positive breast cancer who have undergone chemotherapy and surgery but still have residual cancer. The study compares two groups: one receiving both atezolizumab (an immune-boosting drug) and trastuzumab emtansine, and another receiving a placebo with trastuzumab emtansine. It targets patients diagnosed with HER2-positive breast cancer who have already completed specific preoperative treatments. As of June 4, 2024, the trial is not accepting new participants. As a Phase 3 trial, it represents the final step before potential FDA approval, offering patients a chance to contribute to a treatment nearing widespread availability.

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.

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

Research has shown that trastuzumab emtansine, when combined with atezolizumab, has generally been well-tolerated by patients in past studies. One study found no major improvements in slowing the disease, but the safety profile met expectations. Some patients experienced more side effects with the addition of atezolizumab, though these were usually manageable.

Trastuzumab emtansine has been extensively studied and is an approved treatment for other types of breast cancer, indicating its well-known safety. While the combination may cause additional side effects, the overall safety of trastuzumab emtansine remains well-established. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of atezolizumab and trastuzumab emtansine for breast cancer treatment because it introduces a novel approach to targeting tumors. Atezolizumab is an immunotherapy drug that works by blocking the PD-L1 protein, which helps cancer cells evade the immune system, thereby boosting the body's natural defenses against cancer. Meanwhile, trastuzumab emtansine is an antibody-drug conjugate that targets HER2-positive cancer cells, delivering a chemotherapy agent directly to the tumor while minimizing damage to healthy cells. This dual-action strategy not only enhances the precision of the attack on cancer cells but also has the potential to improve outcomes compared to traditional therapies that often rely solely on chemotherapy or HER2 targeting alone.

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

This trial will compare two treatment arms for HER2-positive breast cancer. In one arm, participants will receive Atezolizumab combined with Trastuzumab Emtansine. Research has shown that adding Atezolizumab to Trastuzumab Emtansine does not significantly extend the time patients live without disease progression, and some studies have found that this combination can cause more side effects without clear benefits. In the other arm, participants will receive a placebo combined with Trastuzumab Emtansine. Trastuzumab Emtansine alone has been effective in treating HER2-positive breast cancer by targeting and killing cancer cells. However, adding Atezolizumab, intended to help the immune system fight cancer, has not shown a meaningful improvement in results. Overall, current evidence does not strongly support the added effectiveness of Atezolizumab in this combination for this condition. ^{2 6 7 8 9}

Who Is on the Research Team?

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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 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]

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 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 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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33002436/

a phase 2, multicentre, randomised, double-blind trial Addition of atezolizumab to trastuzumab emtansine did not show a clinically meaningful improvement in progression-free survival and was associated with more ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02924883

NCT02924883 | A Study to Evaluate the Efficacy and ... This Phase II, double-blind, randomized, placebo-controlled multicenter study will investigate the efficacy and safety of trastuzumab emtansine in combination ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04740918

NCT04740918 | A Study of Trastuzumab Emtansine in ... This study will evaluate the efficacy, safety and patient-reported outcomes of trastuzumab emtansine plus atezolizumab compared with trastuzumab emtansine plus ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36382554/

ASTEFANIA: adjuvant ado-trastuzumab emtansine and ... ASTEFANIA aims to evaluate the efficacy of adjuvant atezolizumab in combination with ado-trastuzumab emtansine in patients with high-risk, HER2-positive early ...

5. genentech-clinicaltrials.com genentech-clinicaltrials.com/en/trials/cancer/bc/a-study-evaluating-the-efficacy-and-safety-of-adjuvant--70278.html

Clinical trial for Breast Cancer, HER2-Positive Breast Ca... A clinical trial to compare the combination of atezolizumab plus trastuzumab emtansine versus trastuzumab emtansine in people with HER2-positive breast cancer.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02924883

NCT02924883 | A Study to Evaluate the Efficacy and ... This Phase II, double-blind, randomized, placebo-controlled multicenter study will investigate the efficacy and safety of trastuzumab emtansine in combination ...

7. annalsofoncology.org annalsofoncology.org/article/S0923-7534(21)02841-6/fulltext

329TiP KATE3: A phase III study of trastuzumab emtansine ... KATE3 (NCT04740918) is an ongoing randomized, multicenter, double-blind, Phase 3 study of T-DM1 with atezolizumab or placebo in trastuzumab- (± pertuzumab) and ...

8. thelancet.com thelancet.com/journals/lanonc/article/PIIS1470-2045(20)30465-4/abstract

Trastuzumab emtansine plus atezolizumab versus ... Safety of trastuzumab emtansine (T-DM1) in patients with HER2-positive advanced breast cancer: primary results from the KAMILLA study cohort 1. Eur J Cancer.

9. genentech-clinicaltrials.com genentech-clinicaltrials.com/en/trials/cancer/bc/a-study-of-trastuzumab-emtansine-in-combination-with-at-19708.html

Clinical Trial – Breast Cancer – Efficacy and Safety of T... Access the clinical trial that will evaluate the efficacy, safety, pharmacokinetics, and patient-reported outcomes of trastuzumab emtansine plus atezolizumab c.