Ado-Trastuzumab Emtansine for Cancer

Not currently recruiting at 7 trial locations

Overseen By Gopakumar Iyer, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Anthracyclines

Disqualifiers: Heart failure, Myocardial infarction, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how the drug ado-trastuzumab emtansine (Kadcyla) affects various cancers linked to the abnormal HER2 gene. It includes groups of participants with specific cancer types, such as lung, colorectal, endometrial, and salivary gland cancers. Suitable candidates are those with advanced solid tumors and either a HER2 mutation or amplification, as identified by specific tests. The trial aims to understand the drug's effects on these cancers and its potential to control their growth. As a Phase 2 trial, the research focuses on measuring 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 if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that ado-trastuzumab emtansine is likely to be safe for humans?

Research shows that ado-trastuzumab emtansine (T-DM1), a treatment under study for various cancers, has a well-established safety record. The FDA has already approved it for treating HER2-positive breast cancer, confirming its safety for that specific cancer. However, more unwanted effects have been reported with T-DM1 compared to trastuzumab alone. Common side effects include fatigue, nausea, and muscle pain. Some studies also mention a higher risk of serious side effects, such as low platelet levels, which could lead to more hospital visits. Overall, while the drug has been effective and is generally considered safe, it does have possible side effects that participants should consider when deciding to join a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for cancer?

Ado-trastuzumab emtansine is unique because it combines a targeted therapy with a chemotherapy agent. Unlike standard treatments for cancers like lung, colorectal, and endometrial, which often involve separate chemotherapy and targeted therapies, ado-trastuzumab emtansine delivers both in one package. This treatment specifically targets HER2-positive cancer cells, releasing the chemotherapy agent directly inside them, which can potentially enhance effectiveness and reduce side effects compared to traditional approaches. Researchers are excited about its potential to improve outcomes in cancers that overexpress the HER2 protein, offering a more precise and powerful treatment option.

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

This trial will evaluate ado-trastuzumab emtansine across various cancer types. Research has shown that ado-trastuzumab emtansine holds promise for treating cancers linked to the HER2 gene. In the cohort for HER2-mutant lung cancer, nearly half of the patients experienced tumor shrinkage. In the cohort for salivary gland cancers, it achieved the highest response rates and showed promising results. For colorectal cancer, it slowed tumor growth, especially in smaller tumors. In the cohort for endometrial cancers, the treatment showed early signs of effectiveness, similar to its success in treating HER2-positive breast cancer. Overall, ado-trastuzumab emtansine appears effective in reducing tumors in several cancer types, particularly those with HER2 mutations or amplifications. ^{2 6 7 8 9}

Who Is on the Research Team?

Jamie E Chaft, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• ado-trastuzumab emtansine

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.

How Is the Trial Designed?

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

ado-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

Approved in European Union as Kadcyla for:

• HER2-positive, metastatic breast cancer

Approved in United Kingdom as Kadcyla for:

• HER2-positive, metastatic breast cancer

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

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

Published Research Related to This Trial

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]

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]

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) 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]

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) 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]

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 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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12399721/

HER2-targeted therapy in colorectal cancer These trials utilizing therapies such as trastuzumab, lapatinib, pertuzumab, T-DXd, or tucatinib have shown positive outcomes and improved treatment responses ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10210145/

Ado-tratuzumab emtansine beyond breast cancer The results showed that both T-DM1 and trastuzumab significantly inhibited tumor growth in small tumors. However, in large-volume tumors, trastuzumab does not ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.3020

A phase 2 basket trial of ado-trastuzumab emtansine for ... Results: 88 pts were accrued between 2016 and 2023. The ORR by cohort is listed in Table 1. The most common toxicities were decreased platelet ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2059702920327150

Pertuzumab and trastuzumab emtansine in patients with ... The HERACLES-B trial assessed the efficacy of a HER2-targeted combination of pertuzumab and trastuzumab-emtansine (T-DM1) in chemorefractory mCRC, showing a 9.7 ...

5. aetna.com aetna.com/cpb/medical/data/900_999/0974.html

Ado-trastuzumab Emtansine (Kadcyla) The activity of T-DM1 resulted in a survival benefit (median survival for BT474 tumors: 28 days for trastuzumab versus 112 days for T-DM1, HR = 6.2, 95 % CI: ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6366814/

Ado-Trastuzumab Emtansine for Patients With HER2- ... For the nine patients with HER2-mutant lung cancers without amplification, HER2 protein levels were low or nondetectable. The two patients with concurrent ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT02675829

NCT02675829 | Trial of Ado-Trastuzumab Emtansine for ... 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 ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S0959804921012417

Trastuzumab emtansine for patients with non–small cell ... We have now performed a phase II study to evaluate the efficacy of ado-trastuzumab emtansine (T-DM1) for NSCLC positive for HER2 exon-20 insertion mutations.

9. pubs.acs.org pubs.acs.org/doi/10.1021/jm500766w

Ado-trastuzumab Emtansine (T-DM1): An Antibody–Drug ... The “EMILIA” trial established the safety and effectiveness of T-DM1, and it was approved as a new therapy for patients with HER2-positive late ...