T-DM1 for Breast Cancer

Not currently recruiting at 96 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Dana-Farber Cancer Institute

Must not be taking: CYP3A4 inhibitors

Disqualifiers: Pregnant, Alcohol, Liver disease, others

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

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 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 28

Duration: 51 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if the drug T-DM1 (trastuzumab emtansine) effectively treats HER2-positive breast cancer and has fewer side effects than the standard treatment of trastuzumab and paclitaxel. Researchers are testing whether T-DM1 can prevent breast cancer recurrence, as it has shown promise in lab studies by killing cancer cells. The trial is suitable for individuals with confirmed HER2-positive breast cancer who have recently undergone surgery and meet specific criteria, such as having all cancer removed and no history of invasive breast cancer. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must stop any investigational drugs at least 2 weeks before joining. You cannot use potent CYP3A4 inhibitors during the study.

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

Research shows that trastuzumab emtansine (T-DM1) is generally well-tolerated by patients with HER2-positive metastatic breast cancer. Studies have demonstrated that this drug can lower the risk of cancer returning or worsening. For example, one study found that T-DM1 reduced the chance of cancer recurrence by about 50% compared to other treatments.

Regarding safety, real-world data and clinical observations indicate that T-DM1 has a manageable safety profile. Most patients experience mild to moderate side effects, such as tiredness, nausea, and low platelet counts. Serious side effects are less common but can occur.

The FDA has already approved this drug for treating metastatic HER2-positive breast cancer, indicating it has passed strict safety checks for that condition. While researchers continue to study T-DM1 for use in other types of breast cancer, including the focus of this trial, its existing approval offers some reassurance about its safety. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for breast cancer?

Unlike the standard of care for breast cancer, which often involves combinations like paclitaxel and trastuzumab, trastuzumab emtansine (T-DM1) offers a unique approach. T-DM1 combines trastuzumab with a chemotherapy agent, delivering targeted treatment directly to cancer cells while minimizing damage to healthy tissue. This mechanism not only enhances effectiveness but also potentially reduces side effects compared to traditional chemotherapy. Researchers are excited about T-DM1 because it represents a smarter, more precise way to treat breast cancer, promising better outcomes for patients.

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

Research shows that trastuzumab emtansine (T-DM1), which participants in this trial may receive, can effectively treat HER2-positive breast cancer. One study found that patients using T-DM1 had a 50% lower chance of cancer recurrence or death compared to those receiving standard treatment. Another study found that more patients survived when taking T-DM1, with 89.1% living compared to 84.4% who took trastuzumab alone. However, T-DM1 caused more side effects, affecting about 26.1% of patients. This evidence suggests that T-DM1 may improve survival and reduce cancer recurrence, but it may also lead to more side effects. Meanwhile, the combination of Paclitaxel and Trastuzumab serves as an active comparator in this trial. ^{1 4 6 7 8}

Who Is on the Research Team?

Sara Tolaney, MD, MPH

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

This trial is for individuals with HER2-positive Stage I breast cancer, who have had recent surgery and may have started hormonal therapy. They must not be pregnant or breastfeeding, free from certain other cancers for 5 years, without active infections or liver disease, and agree to use effective contraception.

Inclusion Criteria

All margins should be clear of invasive cancer or DCIS

Must have discontinued any investigational drug at least 2 weeks prior to participation

I have had my ovaries removed to prevent cancer.

Exclusion Criteria

Excessive alcohol intake (more than 3 alcoholic beverages per day)

I have had chemotherapy within the last 5 years.

I have an active liver condition.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive either T-DM1 every three weeks for 51 weeks or Paclitaxel and Trastuzumab weekly for 12 weeks followed by Trastuzumab every three weeks for 39 weeks

51 weeks

17 visits (in-person) for T-DM1 group, 25 visits (in-person) for Paclitaxel/Trastuzumab group

Radiation

Participants who undergo lumpectomy receive breast radiation therapy; those with mastectomy may receive chest wall and lymph node radiation

6-8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment with regular visits every 6 months for 3 years, then annually for 2 years

5 years

10 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Paclitaxel
• Trastuzumab
• Trastuzumab emtansine

Trial Overview The ATEMPT trial is testing the effectiveness of T-DM1 (an investigational drug) against the standard treatment combination of paclitaxel and trastuzumab in preventing breast cancer recurrence. It's a Phase II study comparing side effects and long-term benefits.

How Is the Trial Designed?

Group I: Paclitaxel + Trastuzumab Active Control 2 Interventions

paclitaxel 80 mg/m2 IV weekly and trastuzumab 4 mg/kg IV load, followed by 2 mg/kg IV weekly for 12 weeks, followed by trastuzumab 6 mg/kg IV every 3 weeks for 13 treatments

Group II: Trastuzumab emtansine (T-DM1) Active Control 1 Intervention

T-DM1 3.6mg/kg every three weeks by IV for 17 doses for a total of 51 weeks

Trastuzumab emtansine is already approved in United States, European Union, United Kingdom for the following indications:

Approved in United States as Kadcyla for:

• HER2-positive metastatic breast cancer
• HER2-positive early breast cancer with residual invasive disease after neoadjuvant taxane and trastuzumab-based treatment

Approved in European Union as Kadcyla for:

• HER2-positive metastatic breast cancer
• HER2-positive early breast cancer with residual invasive disease after neoadjuvant taxane and trastuzumab-based treatment

Approved in United Kingdom as Kadcyla for:

• HER2-positive metastatic breast cancer
• HER2-positive early breast cancer with residual invasive disease after neoadjuvant taxane and trastuzumab-based treatment

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

Published Research Related to This Trial

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]

Ado-trastuzumab emtansine (T-DM1) was approved in the U.S. for treating HER2 positive metastatic breast cancer based on the EMILIA phase III trial, which showed it was more effective than the standard treatment of lapatinib plus capecitabine.

Ongoing and planned trials are exploring T-DM1's use in various stages of breast cancer, and the review discusses its toxicity management and potential resistance mechanisms, highlighting its importance in current cancer treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ado-trastuzumab emtansine (T-DM1) in human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer: latest evidence and clinical potential. Peddi, PF., Hurvitz, SA.[2022]

In a study of 128 patients with advanced HER2+ breast cancer treated with ado-trastuzumab emtansine (T-DM1), the median progression-free survival was 8.7 months and overall survival was 20.4 months, indicating its efficacy in a real-world setting.

The safety profile of T-DM1 was consistent with existing literature, but the study noted higher rates of peripheral neuropathy (21.9%) and liver toxicity (19.5%), which are important considerations for its use in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of T-DM1 in patients with advanced HER2-positive breast cancer The Royal Marsden experience. Battisti, NML., Rogerson, F., Lee, 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]

Ado-trastuzumab emtansine (T-DM1) is an antibody-drug conjugate that effectively targets HER2-positive breast cancer while minimizing off-target side effects, combining the benefits of targeted therapy with potent cytotoxic action.

T-DM1 has shown significant improvements in patient prognosis when used in neoadjuvant therapy and as a rescue treatment for advanced breast cancer, with ongoing clinical trials exploring its efficacy in other solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical research progress of T-DM1 in breast cancer]. Li, LX., Ma, F.[2021]

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]

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]

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]

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]

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]

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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10232689/

Retrospective Observational Study of Outcomes in HER2 ... Patients treated with ado-trastuzumab emtansine (T-DM1) in this study had more advanced breast cancer than patients treated in the clinical ...

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

Clinical Trial Results for KADCYLA® (ado-trastuzumab ... Based on limited data from a retrospective observational study, 22% (7 of 32) of patients with HER2-positive MBC with a baseline LVEF of 40-49% treated with ...

4. 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 ...

5. upmc.com upmc.com/media/news/011525-trastuzumab

Trastuzumab Emtansine Improves Overall Survival in ... Overall survival was 89.1% with T-DM1 and 84.4% with trastuzumab alone. Although adverse events were higher in the T-DM1 group (26.1%) compared ...

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

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.

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

Safety, efficacy and survival outcome of Ado-trastuzumab ... Retrospective observational study of outcomes in HER2-positive metastatic breast cancer patients treated with trastuzumab emtansine in single ...

8. 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 ...