T-DM1 for Breast Cancer

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

82 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug T-DM1 for breast cancer?

T-DM1 has been shown to improve 3-year invasive disease-free survival rates in patients with HER2-positive early breast cancer, with 88.3% of patients remaining disease-free compared to 77.0% with trastuzumab alone. This suggests that T-DM1 is effective in treating HER2-positive breast cancer, especially in those who have residual disease after initial treatments. ^{1 2 3 4 5}

Is T-DM1 (Trastuzumab emtansine, Kadcyla) safe for humans?

T-DM1 has been studied in patients with HER2-positive breast cancer and generally shows a favorable safety profile, though some patients may experience side effects like skin reactions or other adverse events. It has been compared to other treatments and found to have improved tolerability in some studies. ^{6 7 8 9 10}

What makes the drug T-DM1 unique for treating HER2-positive breast cancer?

T-DM1 is unique because it is an antibody-drug conjugate that combines trastuzumab, which targets HER2-positive cancer cells, with a powerful chemotherapy agent called DM1. This combination allows T-DM1 to deliver the chemotherapy directly to the cancer cells, potentially reducing damage to healthy cells and offering a treatment option for patients whose cancer has not responded to trastuzumab alone. ^{1 5 7 9 11}

What is the purpose of this trial?

This research study is studying an investigational drug as a possible treatment for breast cancer that is positive for the protein Human Epidermal Growth Factor Receptor 2, also known as HER2-positive breast cancer. The drug involved in this study is: -ado-trastuzumab emtansine (T-DM1)

Research Team

Rachel Freedman, MD

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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) 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 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 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]

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]

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]

References

1. England 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). [2023]

2. England pubmed.ncbi.nlm.nih.gov

The EMA review of trastuzumab emtansine (T-DM1) for the adjuvant treatment of adult patients with HER2-positive early breast cancer. [2021]

3. Greece pubmed.ncbi.nlm.nih.gov

T-DM1 as a New Treatment Option for Patients with Metastatic HER2-positive Breast Cancer in Clinical Practice. [2019]

4. 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]

5. England pubmed.ncbi.nlm.nih.gov

Trastuzumab emtansine (T-DM1) for HER2-positive breast cancer. [2022]

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

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

7. 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]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Acute skin radiation toxicity seen with concurrent T-DM1: A single institutional report of 35 patients. [2023]

9. Singapore pubmed.ncbi.nlm.nih.gov

Biological Evaluation of Maytansinoid-Based Site-Specific Antibody-Drug Conjugate Produced by Fully Chemical Conjugation Approach: AJICAP®. [2022]

10. 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]

11. England pubmed.ncbi.nlm.nih.gov

Application of trastuzumab emtansine in HER-2-positive and KRAS/BRAF-mutated colon cancer cells. [2020]