Ado-Trastuzumab Emtansine for Cancer

Recruiting in Palo Alto (17 mi)

+7 other locations

Overseen by Jamie E Chaft, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Anthracyclines

Disqualifiers: Heart failure, Myocardial infarction, Neuropathy, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

The purpose of this study is to find out what effects, a drug called ado-trastuzumab emtansine has on the patient and their cancer which is thought to be controlled by the abnormal HER2 gene.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug ado-trastuzumab emtansine (Kadcyla) for cancer?

Ado-trastuzumab emtansine (Kadcyla) has been shown to be effective for HER2-positive metastatic breast cancer, as demonstrated in the EMILIA trial, where it was compared to other treatments and showed significant benefits. It combines targeted therapy with a powerful anti-cancer drug, improving outcomes for patients with advanced breast cancer. ^{1 2 3 4 5}

Is ado-trastuzumab emtansine (Kadcyla) generally safe for humans?

Ado-trastuzumab emtansine (Kadcyla) has been studied in several clinical trials for HER2-positive breast cancer, showing it is generally well tolerated, but some patients may experience side effects that require dose adjustments. Common side effects include fatigue, nausea, and low platelet counts, and more serious side effects can occur, so monitoring by healthcare professionals is important. ^{1 4 5 6 7}

What makes the drug ado-trastuzumab emtansine unique for cancer treatment?

Ado-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 while minimizing damage to healthy cells, which reduces side effects compared to traditional chemotherapy. ^{1 2 8 9 10}

Research Team

Jamie E Chaft, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

This trial is for adults with advanced solid tumors linked to HER2 gene changes, who are in good physical condition (Karnofsky Performance Status ≥70%), have adequate blood cell counts, and agree to use effective contraception. It's not for those who've had ado-trastuzumab emtansine before, are pregnant/breastfeeding, have certain heart conditions or lung diseases, or severe allergies to the drug's components.

Inclusion Criteria

You are able to perform daily activities with some difficulty.

Your blood platelet count is at least 100,000 per microliter within 30 days before the start of the study.

Women of childbearing potential must agree to use of a highly effective method of contraception. Effective contraception is required during treatment and for 7 months following the last dose for female participants of reproductive potential and during treatment and for 4 months following the last dose for male participants with female sexual partners of reproductive potential. Male participants should also refrain from donating sperm during treatment and for 4 months following the last dose

Exclusion Criteria

You have a type of irregular heart rhythm that needs to be treated and is not currently stable.

Women who are pregnant or breast-feeding

You have had a lung disease called interstitial lung disease or pneumonitis in the past.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ado-trastuzumab emtansine to assess its effects on HER2 amplified or mutant cancers

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• ado-trastuzumab emtansine (Monoclonal Antibodies)

Trial Overview The study tests the effects of ado-trastuzumab emtansine on cancers thought to be driven by abnormal HER2 genes. Participants must have measurable cancer signs and meet specific genetic criteria confirmed by a certified lab. The trial includes various cohorts based on different types of HER2 mutations or amplifications.

Participant Groups

Group I: Cohort 6: Other solid cancers Experimental Treatment 1 Intervention

Group II: Cohort 5: Salivary gland cancers Experimental Treatment 1 Intervention

Group III: Cohort 4: Endometrial cancers Experimental Treatment 1 Intervention

Group IV: Cohort 3: Colorectal cancers Experimental Treatment 1 Intervention

Group V: Cohort 2: Lung cancers, HER2 amplified Experimental Treatment 1 Intervention

Group VI: Cohort 1: Lung cancers, HER2 mutant Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Lisa M. DeAngelis

Memorial Sloan Kettering Cancer Center

Chief Medical Officer since 2021

MD from Columbia University

Selwyn M. Vickers

Memorial Sloan Kettering Cancer Center

Chief Executive Officer since 2022

MD from Johns Hopkins University

Genentech, Inc.

Industry 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

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]

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]

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]

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]

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]

In a study of 93 older women (aged 65 and above) with advanced HER2-positive breast cancer treated with ado-trastuzumab emtansine (T-DM1), the median overall survival was 15.0 months, indicating that T-DM1 is an effective treatment option for this age group.

The treatment was generally well-tolerated, with 92.5% of patients experiencing adverse events, but only 30.1% having severe (grade 3 or 4) events, suggesting that while side effects are common, they are manageable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of trastuzumab emtansine in older patients with HER2-positive advanced breast cancer: a real-world study. Cil, I., Kucukarda, A., Atcı, MM., et al.[2022]

Ado-trastuzumab emtansine (T-DM1) pharmacokinetics in patients with HER2-positive advanced gastric cancer was best described by a two-compartment model, indicating complex drug distribution and elimination processes.

Patient characteristics, specifically body weight and baseline trastuzumab concentrations, significantly influenced T-DM1 clearance and distribution, suggesting that these factors should be considered for optimizing treatment in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Population pharmacokinetics of trastuzumab emtansine in previously treated patients with HER2-positive advanced gastric cancer (AGC). Chen, SC., Kagedal, M., Gao, Y., et al.[2019]

Ado-trastuzumab emtansine (T-DM1) is an effective treatment for advanced HER2-positive breast cancer, showing superior response rates and longer progression-free survival compared to the lapatinib/capecitabine combination in Phase III trials.

T-DM1 not only retains the action of trastuzumab but also delivers a cytotoxic agent directly to tumor cells, leading to improved tolerability and quality of life for patients who have previously undergone treatment with trastuzumab and a taxane.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab emtansine in advanced human epidermal growth factor receptor 2-positive breast cancer. Van den Mooter, T., Teuwen, LA., Rutten, A., et al.[2019]

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

Safety and efficacy of T-DM1 in patients with advanced HER2-positive breast cancer The Royal Marsden experience. [2021]

4. 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]

5. Singapore pubmed.ncbi.nlm.nih.gov

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

6. 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]

7. New Zealand pubmed.ncbi.nlm.nih.gov

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

8. United States pubmed.ncbi.nlm.nih.gov

Efficacy and safety of trastuzumab emtansine in older patients with HER2-positive advanced breast cancer: a real-world study. [2022]

9. Germany pubmed.ncbi.nlm.nih.gov

Population pharmacokinetics of trastuzumab emtansine in previously treated patients with HER2-positive advanced gastric cancer (AGC). [2019]

10. England pubmed.ncbi.nlm.nih.gov

Trastuzumab emtansine in advanced human epidermal growth factor receptor 2-positive breast cancer. [2019]