T-DM1 for Breast Cancer

Not currently recruiting at 14 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Dana-Farber Cancer Institute

Must not be taking: Trastuzumab, Anthracyclines

Disqualifiers: Metastatic disease, Active liver disease, Uncontrolled heart issues, 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

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 7

Duration: 21 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores an investigational drug called ado-trastuzumab emtansine (T-DM1) for treating HER2-positive breast cancer, characterized by cancer cells with an excess of the HER2 protein. The trial aims to evaluate T-DM1's effectiveness against this type of breast cancer. Suitable participants have confirmed HER2-positive breast cancer at stage I-III and have chosen to forgo standard chemotherapy due to concerns about side effects or other reasons. As a Phase 2 trial, this research measures how well T-DM1 works in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, if you are on tamoxifen or other hormonal therapy, you must temporarily stop it before starting the trial and can restart it after six weeks of T-DM1 treatment.

Is there any evidence suggesting that T-DM1 is likely to be safe for humans?

Research has shown that T-DM1 is generally well-tolerated by people with HER2-positive breast cancer. In studies, many patients continued treatment with manageable side effects, while serious side effects were rare. Most side effects were mild to moderate, such as fatigue or nausea. The FDA has approved this drug for other types of breast cancer, indicating a strong safety record. Overall, T-DM1 has proven safe for many patients, but like any treatment, it might not be suitable for everyone. ^{1 2 3 4 5}

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

T-DM1 is unique because it combines trastuzumab, an antibody that targets the HER2 protein, with a potent chemotherapy drug, emtansine, delivering a one-two punch directly to cancer cells. This design allows T-DM1 to specifically target and destroy HER2-positive breast cancer cells while sparing most healthy cells, reducing some side effects typically associated with chemotherapy. Researchers are excited about T-DM1 because it offers a more targeted approach compared to standard treatments like trastuzumab alone or traditional chemotherapy, potentially improving outcomes and quality of life for patients with HER2-positive breast cancer.

What evidence suggests that T-DM1 might be an effective treatment for HER2-positive breast cancer?

Research has shown that T-DM1, also known as ado-trastuzumab emtansine, holds promise for treating HER2-positive breast cancer. Studies indicate that T-DM1 can significantly reduce the risk of cancer recurrence. In one study, patients had a 50% lower chance of their cancer returning or causing death compared to another treatment. Real-world data shows that T-DM1 has a response rate of 75.7%, meaning most patients' tumors shrank or disappeared. These findings suggest that T-DM1 could be an effective option for those with HER2-positive breast cancer. ^{1 2 3 6 7}

Who Is on the Research Team?

Rachel Freedman, MD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

This trial is for individuals aged 60 or older with HER2-positive Stage I-III breast cancer who haven't had metastatic disease, prior invasive breast cancer within 5 years, or certain treatments like neoadjuvant chemotherapy. They must have an ECOG Performance Status of 0-2 and be willing to use birth control and provide blood samples.

Inclusion Criteria

My cancer is HER2 positive, confirmed by tests and a specialist review.

My breast cancer is confirmed and falls within Stage I-III, meeting specific size and node criteria.

I have chosen not to undergo standard chemotherapy or was advised against it.

Exclusion Criteria

My cancer is advanced but hasn't spread far, and my other breast has HER2-negative cancer.

I do not have severe liver, heart, lung diseases, or other serious illnesses.

I am not on any experimental drugs for my cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive T-DM1 intravenously every 3 weeks

21 weeks

7 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

What Are the Treatments Tested in This Trial?

Interventions

• T-DM1

Trial Overview

The ATOP TRIAL is evaluating the investigational drug ado-trastuzumab emtansine (T-DM1) as a potential treatment for patients with HER2-positive breast cancer who either declined standard therapy or are not candidates for it.

How Is the Trial Designed?

Group I: T-DM1 Experimental Treatment 1 Intervention

T-DM1 will be administered every 3 weeks intravenously, with 21 consecutive days defined as a treatment.

T-DM1 is already approved in European Union, United States, Canada, Japan, China for the following indications:

Approved in European Union as Kadcyla for:

• Breast cancer

Approved in United States as Kadcyla for:

• HER2-positive breast cancer

Approved in Canada as Kadcyla for:

• HER2-positive breast cancer

Approved in Japan as Kadcyla for:

• HER2-positive breast cancer

Approved in China as Kadcyla for:

• HER2-positive breast cancer

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

Susan G. Komen Breast Cancer Foundation

Collaborator

Trials

68

Recruited

220,000+

Gateway for Cancer Research

Collaborator

Trials

47

Recruited

2,500+

Published Research Related to This Trial

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 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 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) demonstrated superior inhibitory effects on HER-2-positive colon cancer cells with KRAS/BRAF mutations compared to other treatments like cetuximab and trastuzumab, suggesting its potential as an effective therapy for this challenging cancer type.

The combination of T-DM1 with metformin enhanced the drug's efficacy by increasing caveolin-1 expression, which improved T-DM1 uptake and led to significant tumor growth inhibition in a xenograft mouse model.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Application of trastuzumab emtansine in HER-2-positive and KRAS/BRAF-mutated colon cancer cells. Chung, YC., Chiu, HH., Wei, WC., et al.[2020]

Trastuzumab emtansine (T-DM1) has demonstrated significant efficacy in treating HER2-positive metastatic breast cancer, showing improved progression-free and overall survival compared to standard treatments in the phase III EMILIA trial.

T-DM1 has a favorable safety profile and is being studied in ongoing trials to determine its effectiveness in earlier stages of HER2-positive breast cancer, indicating its potential for broader application in treatment protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab emtansine (T-DM1) for HER2-positive breast cancer. Boyraz, B., Sendur, MA., Aksoy, S., et al.[2022]

In a study of 35 HER2+ breast cancer patients receiving trastuzumab emtansine (T-DM1) with concurrent radiotherapy, a significant number experienced skin toxicity, with 22 patients reporting grade 2 or higher toxicity.

Three patients experienced grade 3 skin toxicities, highlighting the need for careful monitoring of skin reactions in patients undergoing this combined treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute skin radiation toxicity seen with concurrent T-DM1: A single institutional report of 35 patients. Dastgheyb, SS., Kim, K., Doucette, A., et al.[2023]

The novel AJICAP® technology allows for site-specific conjugation of antibodies, resulting in a trastuzumab-maytansinoid ADC that has a higher maximum tolerated dose compared to the commercially available T-DM1, indicating an improved therapeutic index.

Initial safety studies in rats showed that the AJICAP-ADC demonstrated greater stability and tolerability than T-DM1, suggesting it could be a more effective treatment option for HER2-positive metastatic breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biological Evaluation of Maytansinoid-Based Site-Specific Antibody-Drug Conjugate Produced by Fully Chemical Conjugation Approach: AJICAP®. Seki, T., Yamada, K., Ooba, Y., et al.[2022]

In a study of 128 female patients with HER2-positive metastatic breast cancer who previously received trastuzumab emtansine (T-DM1), the median progression-free survival (rwPFS) was 5.7 months, indicating some effectiveness of post-T-DM1 therapies.

Patients who continued anti-HER2 therapy after T-DM1 had a better median rwPFS of 6.3 months compared to 4.8 months for those who did not, suggesting that ongoing anti-HER2 treatment may provide additional benefits, although overall effectiveness remains limited.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world effectiveness of post-trastuzumab emtansine treatment in patients with HER2-positive, unresectable and/or metastatic breast cancer: a retrospective observational study (KBCSG-TR 1917). Nakayama, T., Yoshinami, T., Yasojima, H., et al.[2023]

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]

Citations

1.

nature.com

nature.com/articles/s41598-025-97923-2

Real-world data on trastuzumab emtansine (TDM1) ...

This study aims to provide real-world evidence on the efficacy and safety of TDM1 in HER2-positive MBC patients.

2.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/40437155/

Real-world data on trastuzumab emtansine (TDM1) ...

The median PFS was 6.1 months (95% CI, 4.5-7.6), and the median OS was 14.4 months (95% CI, 10.2-18.0). The objective response rate was 75.7%, ...

3.

nejm.org

nejm.org/doi/full/10.1056/NEJMoa1814017

Trastuzumab Emtansine for Residual Invasive HER2 ...

In this trial, adjuvant treatment with T-DM1 resulted in a 50% lower risk of recurrence of invasive disease or death than adjuvant continuation ...

4.

kadcyla-hcp.com

kadcyla-hcp.com/metastatic-breast-cancer/efficacy/clinical-trial-results.html

Clinical Trial Results for KADCYLA® (ado-trastuzumab ...

Primary analysis: KADCYLA provided proven benefit in OS and PFS · It extended median overall survival (OS) by nearly 6 months · More time without disease ...

5.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC4778787/

Clinical efficacy and safety of T-DM1 for patients with HER2 ...

T-DM1 treatment was associated with 16-month and 18-month PFS rates of 11% and 8% (70/663 and 50/663 patients, respectively, compared with 5% and 3% (33/624 and ...

6.

thegreenjournal.com

thegreenjournal.com/article/S0167-8140(23)00343-2/fulltext

Safety profile of trastuzumab-emtansine (T-DM1) with ...

One such agent is trastuzumab emtansine (T-DM1), an antibody drug conjugate that has shown improved outcomes in both early and advanced breast ...

7.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.e13008

Safety, efficacy and survival outcome of Ado-trastuzumab ...

Overall survival (OS) was calculated from the beginning of treatment with T-DM1 until death from any cause. Results: This study included eighty ...