Trastuzumab Emtansine Safety for Cancer

Recruiting at 323 trial locations

Overseen By Reference Study ID Number: BO25430 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Genentech, Inc.

Must be taking: Trastuzumab emtansine

Disqualifiers: Severe neuropathy, Heart failure, 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 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Until disease progression or unacceptable toxicity

720 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety of a cancer treatment called trastuzumab emtansine. It targets individuals who participated in an earlier study and continue to benefit from the treatment. The trial aims to determine if continuing this treatment, either alone or with other cancer drugs, can maintain its benefits for these participants. Those who have used trastuzumab emtansine and found it effective would be suitable candidates. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It is best to discuss your current medications with the study team to get a clear answer.

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

Research has shown that trastuzumab emtansine, a treatment for certain types of breast cancer, is usually well-tolerated by patients. Some studies indicate that while it can be effective, possible side effects include low platelet counts (thrombocytopenia), heart problems, infections like sepsis, and liver issues (hepatotoxicity).

However, not everyone experiences these side effects, and each person's experience can differ. Prospective trial participants should consult a doctor to discuss the potential benefits and risks based on their health situation. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Trastuzumab emtansine is unique because it combines a targeted therapy with a chemotherapy agent, specifically designed for HER2-positive cancers. Unlike traditional chemotherapy, which can attack both healthy and cancerous cells, trastuzumab emtansine targets the HER2 protein on cancer cells, delivering chemotherapy directly to them and minimizing damage to healthy cells. This targeted approach not only aims to enhance effectiveness but also reduces some of the side effects commonly associated with standard treatments like trastuzumab and chemotherapy combinations. Researchers are excited about this treatment because it represents a more precise way to tackle cancer, potentially leading to better outcomes and improved quality of life for patients.

What evidence suggests that trastuzumab emtansine might be an effective treatment for cancer?

Research has shown that trastuzumab emtansine, or T-DM1, effectively treats HER2-positive breast cancer. In one study, patients using T-DM1 had a 50% lower chance of cancer recurrence compared to those on other treatments. Another study found that patients on T-DM1 lived longer than those taking a different drug combination. Real-world evidence also supports T-DM1's effectiveness and safety for patients with advanced HER2-positive breast cancer. In this trial, participants will receive trastuzumab emtansine either as a single agent or in combination with other anti-cancer therapies. Overall, T-DM1 has shown promise in extending patient survival and reducing cancer recurrence. ^{1 4 6 7 8}

Who Is on the Research Team?

Clinical Trials

Principal Investigator

Genentech, Inc.

Are You a Good Fit for This Trial?

This trial is for cancer patients who were previously treated with Trastuzumab Emtansine alone or in combination with other therapies in a related study and are still benefiting. They must not have severe heart issues, uncontrolled diseases, recent major surgeries, current pregnancy/lactation, certain drug allergies, high-grade peripheral neuropathy, or specific adverse reactions from previous treatments.

Inclusion Criteria

I am willing to use effective birth control during and after the study.

I was in a control group for a previous study and my condition worsened, now I can start a new treatment.

My doctor believes I could benefit from more trastuzumab emtansine treatment.

Exclusion Criteria

Inability or unwillingness to comply with the protocol requirements

I do not have any severe, uncontrolled illnesses.

I have not had major surgery or a serious injury in the last 28 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive trastuzumab emtansine as a single agent or in combination with other anti-cancer therapies in 21-day cycles or weekly, depending on the schedule used in the parent study

Until disease progression or unacceptable toxicity

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Participants continue to receive treatment as long as they are benefiting from it

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Pertuzumab
• Trastuzumab
• Trastuzumab Emtansine

Trial Overview The trial continues treatment with Trastuzumab Emtansine for those showing benefits from prior studies. It's an open-label extension meaning everyone knows what treatment they're getting. The aim is to assess long-term safety of the drug used alone or with other anti-cancer agents like Paclitaxel and Atezolizumab.

How Is the Trial Designed?

Group I: Trastuzumab Emtansine Experimental Treatment 6 Interventions

Participants will receive trastuzumab emtansine either as a single agent or in combination with other anti-cancer therapy (atezolizumab, paclitaxel, trastuzumab and docetaxel). Participants will receive the same dose and schedule on Cycle 1, Day 1 at which it was given at the end of the parent study. Study drug will be administered in 21-day cycles or weekly, depending on the schedule used in the parent study. Participants will receive study treatment until disease progression or unacceptable toxicity.

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

Approved in United States as Kadcyla for:

• Metastatic breast cancer in patients whose tumors overexpress the HER2 protein and who have received prior therapy with trastuzumab and a taxane, either separately or in combination.
• Adjuvant treatment of patients with HER2-positive early breast cancer (EBC) who have residual invasive disease after neoadjuvant taxane and trastuzumab-based treatment

Approved in European Union as Kadcyla for:

• Metastatic breast cancer in patients whose tumors overexpress the HER2 protein and who have received prior therapy with trastuzumab and a taxane, either separately or in combination.

Approved in United Kingdom as Kadcyla for:

• Metastatic breast cancer in patients whose tumors overexpress the HER2 protein and who have received prior therapy with trastuzumab and a taxane, either separately or in combination.

Who Is Running the Clinical Trial?

Genentech, Inc.

Lead Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Hoffmann-La Roche

Industry 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

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]

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 (Kadcyla®) is effective in reducing the risk of invasive disease recurrence or death by 50% compared to trastuzumab in patients with HER2-positive early breast cancer after neoadjuvant treatment, as shown in the KATHERINE trial.

The safety profile of trastuzumab emtansine is consistent with previous findings, with more adverse events reported compared to trastuzumab, leading to its recommendation as a preferred treatment option in updated guidelines for high-risk breast cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab Emtansine: A Review of Its Adjuvant Use in Residual Invasive HER2-Positive Early Breast Cancer. Lyseng-Williamson, KA.[2022]

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]

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 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]

In a study of 893 HER2+ advanced breast cancer patients treated with ado-trastuzumab emtansine (T-DM1), early adverse events that required dose interruptions or reductions did not significantly affect overall survival (OS) or progression-free survival (PFS).

The analysis, using data from the EMILIA and TH3RESA clinical trials, indicated that early dose adjustments due to adverse events are not linked to worse long-term outcomes, suggesting that T-DM1 remains an effective treatment option even when dose modifications are necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of early adverse events resulting in ado-trastuzumab emtansine dose adjustments on survival outcomes of HER2+ advanced breast cancer patients. Tang, E., Rowland, A., McKinnon, RA., et al.[2020]

Citations

1. 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 ...

2. 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.

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. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33095031/

Comparative effectiveness of trastuzumab emtansine ... Overall survival was longer in patients treated with T-DM1 than those treated with lapatinib plus chemotherapy (adjusted hazard ratio: 0.56; 95% ...

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

8. sciencedirect.com sciencedirect.com/science/article/pii/S2949820124000237

Utilization and safety of trastuzumab emtansine (T-DM1) We also found that T-DM1 users had a significantly higher risk of being hospitalized for thrombocytopenia, cardiac disease, sepsis and hepatotoxicity than the ...