T-DM1 + Tucatinib for Breast Cancer
Palo Alto (17 mi)Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: Alliance for Clinical Trials in Oncology
No Placebo Group
Pivotal Trial (Near Approval)
Prior Safety Data
Breakthrough Therapy
Approved in 3 jurisdictions
Trial Summary
What is the purpose of this trial?This phase III trial studies how well trastuzumab emtansine (T-DM1) and tucatinib work in preventing breast cancer from coming back (relapsing) in patients with high risk, HER2 positive breast cancer. T-DM1 is a monoclonal antibody, called trastuzumab, linked to a chemotherapy drug, called DM1. Trastuzumab is a form of targeted therapy because it attaches to specific molecules (receptors) on the surface of cancer cells, known as HER2 receptors, and delivers DM1 to kill them. Tucatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving T-DM1 and tucatinib may work better in preventing breast cancer from relapsing in patients with HER2 positive breast cancer compared to T-DM1 alone.
Do I need to stop my current medications for the trial?The trial protocol does not specify if you need to stop taking your current medications. However, you cannot use strong CYP3A4 or CYP2C8 inhibitors within 2 weeks before registration or strong CYP3A4 or CYP2C8 inducers within 5 days prior. Sensitive CYP3A substrates should be avoided two weeks before registration and during the study. Please consult with your doctor for specific guidance.
Is the drug Trastuzumab Emtansine (T-DM1) a promising treatment for breast cancer?Yes, Trastuzumab Emtansine (T-DM1) is a promising drug for treating breast cancer. It combines targeted therapy with powerful cancer-fighting agents, improving outcomes for patients with HER2-positive breast cancer. It has shown effectiveness in both early and advanced stages of the disease.13579
What safety data is available for T-DM1 and Tucatinib in breast cancer treatment?The safety profile of T-DM1 (Trastuzumab Emtansine) has been evaluated in several studies. The EMILIA trial compared T-DM1 to capecitabine plus lapatinib, showing significant differences in safety profiles. T-DM1 is generally well tolerated, but adverse events can occur, sometimes requiring dose adjustments. A case report highlighted a fatal reaction of acute eosinophilic pneumonia linked to T-DM1. Safety evaluations in Japanese patients also confirmed its tolerability. However, specific safety data for the combination of T-DM1 and Tucatinib is not detailed in the provided research.3461112
What data supports the idea that T-DM1 + Tucatinib for Breast Cancer is an effective drug?The available research shows that T-DM1, a component of the T-DM1 + Tucatinib treatment, is effective for HER2-positive breast cancer. It is used as a standard treatment for advanced cases and has shown to improve patient outcomes. For instance, T-DM1 is effective in patients who have not responded to other treatments, as it targets cancer cells more precisely and reduces side effects. Additionally, T-DM1 has been approved based on a large study that demonstrated its effectiveness compared to other treatments. While specific data on the combination with Tucatinib is not detailed, the effectiveness of T-DM1 alone suggests potential benefits when used together.278910
Eligibility Criteria
This trial is for patients with high risk, HER2 positive breast cancer who have had some treatment but still have invasive disease. They should not be pregnant or nursing and must not have metastatic (stage IV) breast cancer or a history of severe allergies to the drugs used in this study. Participants need good heart function and cannot have had another invasive breast cancer within the last 3 years.Inclusion Criteria
My breast and lymph node cancer has been fully removed.
My last major treatment was within the last 3 months.
My surgery report shows HR-negative, HER2 positive cancer in breast or lymph nodes.
My biopsy shows my cancer is HER2-positive with a high score.
My breast cancer is slightly estrogen receptor-positive.
My cancer was at an early or advanced stage when found and still present after surgery.
Both of my breast cancer lesions are HER2 positive.
My cancer is either estrogen or progesterone receptor positive, or both are negative.
My cancer's hormone receptor status is known.
I received specific chemotherapy before surgery.
My breast cancer was at stage T1-4, N0-3 at diagnosis and I still have invasive disease after surgery.
I have received 1 or fewer cycles of T-DM1 for early-stage treatment.
My cancer is HER2-positive based on a biopsy.
I am fully active or can carry out light work.
Exclusion Criteria
My nerve damage does not severely affect my daily activities.
My cancer is ER+ and HER2+, has spread but not to my lymph nodes.
My breast cancer has spread to other parts of my body.
I haven't taken any experimental cancer drugs in the last 28 days.
I do not have any severe, uncontrolled diseases.
I do not have active or untreated hepatitis B, C, or chronic liver disease.
My cancer has come back after initial treatment and surgery.
I haven't had major surgery or serious injuries in the last 28 days.
I cannot undergo radiotherapy due to health reasons.
My heart and lung function is normal.
I have not had invasive breast cancer in the last 3 years.
I have been treated with a specific amount of anthracycline drugs.
Treatment Details
The trial is testing if combining T-DM1 (a targeted therapy that delivers chemo directly to cancer cells) with tucatinib (which blocks enzymes needed for tumor growth) prevents relapse better than T-DM1 alone in those at high risk of their HER2 positive breast cancer returning.
2Treatment groups
Experimental Treatment
Active Control
Group I: Arm II (trastuzumab emtansine, tucatinib)Experimental Treatment4 Interventions
Patients receive T-DM1 IV over 30-90 minutes on day 1 and tucatinib PO BID on days 1-21. Treatment repeats every 21 days for up to 14 cycles in the absence of disease progression or unacceptable toxicity.
Group II: Arm I (trastuzumab emtansine, placebo)Active Control4 Interventions
Patients receive T-DM1 IV over 30-90 minutes on day 1 and placebo PO BID on days 1-21. Treatment repeats every 21 days for up to 14 cycles 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.
Find a clinic near you
Research locations nearbySelect from list below to view details:
Marie Yeager Cancer CenterSaint Joseph, MI
Trinity's Tony Teramana Cancer CenterSteubenville, OH
ProMedica Flower HospitalSylvania, OH
AMG Libertyville - OncologyLibertyville, IL
More Trial Locations
Loading ...
Who is running the clinical trial?
Alliance for Clinical Trials in OncologyLead Sponsor
Seagen Inc.Industry Sponsor
National Cancer Institute (NCI)Collaborator
References
Trastuzumab emtansine (T-DM1) for HER2-positive breast cancer. [2022]Trastuzumab emtansine (T-DM1), a novel drug developed for the treatment of HER2-positive breast cancer, is a human epidermal growth factor receptor (HER2) targeted antibody drug conjugate, composed of trastuzumab, a stable thioether linker, and the potent cytotoxic agent DM1 (derivative of maytansine). It has been shown that, in preclinical studies, it has anti-tumor activity in trastuzumab refractory cancer cells. In this review, we aim to show the clinical data about trastuzumab-DM1 (T-DM1) therapy and to discuss the therapy advantages for the management of patients with HER2-positive breast cancer.
Ado-trastuzumab emtansine (T-DM1) in human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer: latest evidence and clinical potential. [2022]In February 2013, ado-trastuzumab emtansine (T-DM1, Kadcyla®) received regulatory approval in the United States for treatment-refractory human epidermal growth factor receptor 2 (HER2) positive metastatic or locally advanced breast cancer based on results from EMILIA, a large phase III trial that compared standard of care lapatinib plus capecitabine to T-DM1. Several other studies have been reported in the metastatic setting and multiple trials are ongoing or planned in the neoadjuvant, adjuvant and advanced disease settings. Here we provide an updated and comprehensive review of clinical trials evaluating T-DM1, discuss management of toxicity associated with this drug, propose potential mechanisms of resistance and offer practical considerations for the treating oncologist.
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]Trastuzumab emtansine (T-DM1, KADCYLA(®)) is an antibody-drug conjugate comprised of the cytotoxic agent DM1 and trastuzumab (HERCEPTIN(®)). The safety profile of T-DM1 in human epidermal growth factor receptor 2 (HER2)-positive locally advanced or metastatic breast cancer previously treated with trastuzumab and a taxane was investigated in the phase III EMILIA trial. The trial demonstrated clinically and statistically meaningful differences in the safety profile between T-DM1 and capecitabine plus lapatinib (CAP + LAP). The objective of this study was to estimate the costs of managing treatment-related grade ≥ 3 adverse events (AEs) that occurred in ≥ 2% of patients and grade 2 AEs that occurred in ≥ 5% of patients taking T-DM1 compared with patients taking CAP + LAP based on the EMILIA trial, from the perspective of Canadian public payers.
Safety Evaluation of Trastuzumab Emtansine in Japanese Patients with HER2-Positive Advanced Breast Cancer. [2022]Tolerability and safety of trastuzumab emtansine (T-DM1) was investigated in Japanese patients with HER2-positive advanced breast cancer who were previously treated with chemotherapy and trastuzumab.
Tucatinib Combined With Ado-Trastuzumab Emtansine in Advanced ERBB2/HER2-Positive Metastatic Breast Cancer: A Phase 1b Clinical Trial. [2019]Treatment options for patients with disease progression after treatment with trastuzumab, pertuzumab, and ado-trastuzumab emtansine (T-DM1) are limited. Tucatinib is an oral, potent, human epidermal growth factor receptor 2 (HER2)-specific tyrosine kinase inhibitor (TKI) being developed as a novel treatment for ERBB2/HER2-positive breast cancer.
Effect of early adverse events resulting in ado-trastuzumab emtansine dose adjustments on survival outcomes of HER2+ advanced breast cancer patients. [2020]Ado-trastuzumab emtansine (T-DM1) treatment in HER2+ advanced breast cancer patients is generally well tolerated, but when adverse events occur dose adjustments may be required. This study evaluated the impact of early adverse events requiring T-DM1 dose interruptions or reductions on overall survival (OS) and progression-free survival (PFS) in HER2+ advanced metastatic breast cancer patients in the clinical trials EMILIA and TH3RESA.
Application of trastuzumab emtansine in HER-2-positive and KRAS/BRAF-mutated colon cancer cells. [2020]Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate (ADC) for the treatment of human epidermal growth factor receptor 2 (HER-2)-positive breast cancer. T-DM1 is based on the trastuzumab antibody and delivers a toxic agent into breast cancer cells through endocytic mechanism. This study evaluated whether T-DM1 can be used in HER-2-positive colon cancer cells which harbour KRAS/ BRAF mutation with limited treatment.
Safety and efficacy of T-DM1 in patients with advanced HER2-positive breast cancer The Royal Marsden experience. [2021]Ado-trastuzumab emtansine (T-DM1) is standard of care for patients with advanced HER2+ breast cancer who relapse within 6 months of adjuvant trastuzumab or progress on first-line anti-HER2 therapy. We evaluated its safety and efficacy in our real-world population.
[Clinical research progress of T-DM1 in breast cancer]. [2021]Ado-trastuzumab emtansine (T-DM1) is an antibody-drug conjugate (ADC) composed of trastuzumab, a linker, and a microtubule inhibitor. T-DM1 combines the highly effective targeting of antibody with the high anti-tumor activity of cytotoxic drugs, while reduces the off-target toxic side effects of cytotoxic drugs. T-DM1 has been applied in neoadjuvant therapy of HER2-positive breast cancer and rescue treatment of advanced breast cancer, greatly improves the prognosis of breast cancer patients. More and more clinical trials of T-DM1 for HER2 breast cancer and other solid tumors are ongoing, and more positive results are expected.
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]Trastuzumab emtansine (T-DM1) is a second-line standard therapy for patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. Evidence regarding post-T-DM1 treatments is currently lacking. We evaluated the effectiveness of post-T-DM1 drug therapy in patients with HER2-positive, unresectable and/or metastatic breast cancer.
Acute eosinophilic pneumonia: a fatal reaction to ado-trastuzumab. [2023]Ado-trastuzumab emtansine (T-DM1) is a monoclonal antibody drug conjugate approved for the treatment of HER2-positive breast cancers. Presented here is a case report of a patient who developed fatal pulmonary toxicity in the form of acute eosinophilic pneumonia while undergoing treatment with T-DM1. Prior to beginning T-DM1 therapy, this patient had been treated with two HER2-targeted agents (trastuzumab, pertuzumab) per National Comprehensive Cancer Network (NCCN) guidelines. This case represents a novel presentation of toxicity associated with T-DM1 while perhaps demonstrating additive toxicity associated with multiple lines of HER2 targeted therapies.
Biological Evaluation of Maytansinoid-Based Site-Specific Antibody-Drug Conjugate Produced by Fully Chemical Conjugation Approach: AJICAP®. [2022]Trastuzumab-emtansine (T-DM1, commercial name: Kadcyla) is well-known antibody-drug conjugate (ADC) and was first approved for human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. This molecular format consisting of trastuzumab and maytansinoid payload (emtansine) is very simple, however, T-DM1 has wide heterogeneity due to non-specific conjugation, lowering its therapeutic index (TI).