Trastuzumab Emtansine for Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Warfarin, Clopidogrel

Disqualifiers: Breast cancer, Gastric cancer, Neuropathy, 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: 21

Duration: Up to 3 years

38 Participants Needed

Trial Summary

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 cannot be on certain blood thinners like warfarin or long-acting anti-platelet agents like clopidogrel. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug Trastuzumab Emtansine (Kadcyla, T-DM1)?

Trastuzumab Emtansine (T-DM1) has been shown to be effective in treating HER2-positive metastatic breast cancer, as demonstrated in the EMILIA trial, which led to its approval in 2013. It combines targeted therapy with chemotherapy to improve outcomes while reducing side effects, and ongoing trials are exploring its use in other cancer settings. ^{1 2 3 4 5}

Is Trastuzumab Emtansine (Kadcyla) generally safe for humans?

Trastuzumab Emtansine (Kadcyla) has been studied in several clinical trials for HER2-positive breast cancer and is generally well tolerated, but it can cause side effects. Common side effects include liver problems, low blood platelet counts, and nerve damage. Some patients may experience skin reactions when used with radiation therapy. ^{1 4 6 7 8}

What makes the drug Trastuzumab Emtansine unique for treating cancer?

Trastuzumab Emtansine (T-DM1) is unique because it combines a targeted antibody with a powerful cancer-killing drug, allowing it to specifically attack cancer cells with fewer side effects. It is particularly used for HER2-positive breast cancer, where other treatments have failed, and is the only drug of its kind that targets the HER2 protein with both targeting and antitumor properties. ^{1 2 3 4 9}

What is the purpose of this trial?

This phase II MATCH treatment trial identifies the effects of ado-trastuzumab emtansine in patients whose cancer has a genetic change called HER2 amplification. Ado-trastuzumab emtansine is a monoclonal antibody, called trastuzumab, linked to a chemotherapy drug called DM1. Trastuzumab is a form of "targeted therapy", because it works by attaching itself to specific molecules (receptors) on the surface of cancer cells, known as HER2 receptors and delivers DM1 to kill them. Researchers hope to learn if the study drug will shrink this type of cancer or stop its growth.

Research Team

Komal Jhaveri

Principal Investigator

ECOG-ACRIN Cancer Research Group

Eligibility Criteria

This trial is for patients with cancers like lymphoma or solid tumors that have a specific genetic change (HER2 amplification). They must not have had certain prior treatments, agree to use contraception, and meet health criteria such as adequate hemoglobin levels and heart function. People with breast or gastric cancer, severe allergies to the drug being tested, or serious nerve damage are excluded.

Inclusion Criteria

I agree to use effective birth control or abstain from sex during and for 7 months after the study.

Patients must have met applicable eligibility criteria in the Master MATCH Protocol prior to registration to treatment subprotocol

My heart's pumping ability is confirmed to be normal by a recent heart scan.

Exclusion Criteria

I have not been treated with specific FDA-approved or investigational HER2 drugs.

I do not have breast or stomach cancer.

I am not allergic to ado-trastuzumab emtansine or similar drugs.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive trastuzumab emtansine intravenously over 30-90 minutes on day 1, with cycles repeating every 21 days in the absence of disease progression or unacceptable toxicity

Up to 3 years

Every 21 days

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-ups every 3 months if less than 2 years from study entry, and then every 6 months for year 3

Up to 3 years

Treatment Details

Interventions

• Trastuzumab Emtansine

Trial Overview Researchers are testing ado-trastuzumab emtansine in this phase II trial to see if it can shrink tumors or halt their growth in cancers with HER2 changes. This drug combines trastuzumab (a targeted therapy) with a chemotherapy agent DM1 to attack cancer cells directly.

Participant Groups

Group I: Treatment (trastuzumab emtansine) Experimental Treatment 1 Intervention

Patients receive trastuzumab emtansine IV over 30-90 minutes on day 1. Cycles repeat every 21 days in the absence of 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?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

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]

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) 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]

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]

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 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]

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]

References

1. England 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. [2022]

2. China pubmed.ncbi.nlm.nih.gov

[Clinical research progress of T-DM1 in breast cancer]. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Lacrimal drainage system stenosis associated with Trastuzumab emtansine (Kadcyla®, T-DM1) administration: a case report. [2020]

4. Singapore pubmed.ncbi.nlm.nih.gov

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

5. 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]

6. 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]

7. Netherlands 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. [2020]

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. England pubmed.ncbi.nlm.nih.gov

Trastuzumab emtansine: a novel antibody-drug conjugate for HER2-positive breast cancer. [2015]