Tucatinib + T-DM1 for Breast Cancer

Not currently recruiting at 776 trial locations

Overseen By Seagen Trial Information Support

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Seagen Inc.

Must be taking: T-DM1

Must not be taking: Tucatinib, Afatinib

Disqualifiers: Untreated brain lesions, Leptomeningeal disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 21

Duration: Up to 43 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether adding tucatinib, a new drug, to T-DM1 (trastuzumab emtansine, also known as Kadcyla) improves treatment for HER2 positive breast cancer that has spread or cannot be removed with surgery. Participants will receive either tucatinib or a placebo (a pill with no active medicine), along with T-DM1. The researchers aim to determine if tucatinib offers more benefits than T-DM1 alone. This trial may suit those with HER2 positive breast cancer previously treated with specific therapies like taxane and trastuzumab, which has progressed or cannot be treated with surgery. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Do I need to stop my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. However, it does exclude those who have had certain treatments like tucatinib or similar drugs before. It's best to discuss your current medications with the trial team.

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

Research shows that tucatinib, when combined with T-DM1, has been studied for safety in people with HER2-positive breast cancer. Studies have found that this combination is generally well-tolerated. In one study, patients taking tucatinib with T-DM1 experienced manageable side effects, meaning they weren't too severe for most people.

Tucatinib has effectively slowed cancer growth, even in challenging areas like the brain. While side effects were noted, they were expected and similar to those seen in other cancer treatments. Common side effects might include tiredness, nausea, and diarrhea, but these are often not serious.

T-DM1, already approved for treating this type of breast cancer, is also known for its safety. Patients usually tolerate it well, with side effects often including fatigue and nausea.

Overall, both tucatinib and T-DM1 have shown safety for patients with HER2-positive breast cancer, with generally manageable side effects. ^{1 2 3 4 5}

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

Researchers are excited about the combination of Tucatinib and T-DM1 for breast cancer because it offers a novel approach by targeting HER2-positive cancer cells more precisely. Unlike standard treatments, which often involve broad-spectrum chemotherapy, Tucatinib is a targeted therapy that inhibits the HER2 protein, potentially reducing tumor growth with fewer side effects. When combined with T-DM1, an antibody-drug conjugate that delivers chemotherapy directly to cancer cells, this treatment aims to enhance efficacy while minimizing damage to healthy cells. This targeted action could lead to better outcomes for patients with HER2-positive breast cancer, a significant advancement over traditional treatment options.

What evidence suggests that this trial's treatments could be effective for HER2 positive breast cancer?

This trial will compare the combination of Tucatinib and T-DM1 with a placebo and T-DM1 for treating HER2-positive breast cancer. Studies have shown that adding Tucatinib to T-DM1 can be effective, particularly for cancer that has metastasized or cannot be surgically removed. Evidence from previous studies indicates that this combination can help control cancer, even in difficult cases such as those with brain metastases. Overall, using Tucatinib and T-DM1 together has led to better outcomes for patients with this type of breast cancer. ^{1 3 4 6 7}

Who Is on the Research Team?

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Are You a Good Fit for This Trial?

This trial is for adults with advanced or metastatic HER2+ breast cancer that has worsened after previous treatment or if they couldn't tolerate the last therapy. They should be relatively healthy (ECOG score of 0 or 1) and may have brain metastases if stable, treated, or not requiring immediate intervention. People can't join if they've had certain recent anti-HER2 treatments, large untreated brain lesions, need high-dose steroids for brain symptoms, have leptomeningeal disease, or uncontrolled seizures.

Inclusion Criteria

I am fully active or can carry out light work.

I have been treated with both a taxane and trastuzumab before.

My brain scan shows I may have brain metastases but don't need immediate treatment, or I've been treated for them and am stable or not needing immediate re-treatment.

Exclusion Criteria

I do not have large untreated brain lesions, uncontrolled seizures, or need high doses of steroids for brain symptoms.

I have not been treated with specific HER2 or EGFR targeting drugs recently.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive tucatinib or placebo in combination with T-DM1 in 21-day cycles

Up to 43 months

Every 21 days for T-DM1 injections

Progression Assessment

Participants are assessed for disease progression every 6 weeks for the first 24 weeks, and every 9 weeks thereafter

Up to 43 months

Follow-up

Participants are monitored for overall survival and progression-free survival after treatment

Up to approximately 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• T-DM1
• Tucatinib

Trial Overview The study tests whether adding tucatinib to T-DM1 (a standard drug for this cancer type) improves outcomes in patients with HER2+ breast carcinoma compared to T-DM1 alone. Participants will either receive tucatinib pills twice daily plus T-DM1 injections every three weeks or placebo pills with T-DM1 injections in a blinded setup where neither patient nor doctor knows which treatment is given.

How Is the Trial Designed?

Group I: Tucatinib + T-DM1 Experimental Treatment 2 Interventions

Tucatinib + T-DM1

Group II: Placebo + T-DM1 Active Control 2 Interventions

Placebo + T-DM1

T-DM1 is already approved in European Union, United States, Canada, Japan, China for the following indications:

Approved in European Union as Kadcyla for:

• Breast cancer

Approved in United States as Kadcyla for:

• HER2-positive breast cancer

Approved in Canada as Kadcyla for:

• HER2-positive breast cancer

Approved in Japan as Kadcyla for:

• HER2-positive breast cancer

Approved in China as Kadcyla for:

• HER2-positive breast cancer

Who Is Running the Clinical Trial?

Seagen Inc.

Lead Sponsor

Trials

212

Recruited

73,800+

Founded

1997

Headquarters

Bothell, USA

Known For

Antibody-Drug Conjugates

Top Products

Adcetris (brentuximab vedotin), Tukysa (tucatinib), Padcev (enfortumab vedotin-ejfv), Tivdak (tisotumab vedotin-tftv)

Dr. Roger Dansey

Seagen Inc.

Chief Medical Officer since 2018

MD from University of Witwatersrand

David R. Epstein

Seagen Inc.

Chief Executive Officer since 2022

BSc in Pharmacy from Rutgers University, MBA from Columbia University

Seagen, a wholly owned subsidiary of Pfizer

Lead Sponsor

Trials

20

Recruited

4,900+

Published Research Related to This Trial

Tucatinib, when combined with T-DM1, was found to have a maximum tolerated dosage of 300 mg twice daily, showing acceptable toxicity levels in a phase 1b trial involving 57 patients with ERBB2/HER2-positive metastatic breast cancer.

The treatment demonstrated preliminary antitumor activity, with most adverse events being mild (grade 1 or 2), although some patients experienced more serious reactions like thrombocytopenia and hepatic transaminitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tucatinib Combined With Ado-Trastuzumab Emtansine in Advanced ERBB2/HER2-Positive Metastatic Breast Cancer: A Phase 1b Clinical Trial. Borges, VF., Ferrario, C., Aucoin, N., et al.[2019]

In a study of 232 Japanese patients with HER2-positive advanced breast cancer, trastuzumab emtansine (T-DM1) was found to be well tolerated, with 98.3% of patients experiencing adverse events but only 2.2% discontinuing treatment due to these events.

The most common serious adverse effects included thrombocytopenia in 29.7% of patients and hepatotoxicity in 11.2%, but no new safety concerns were identified, indicating that T-DM1 is a viable treatment option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Evaluation of Trastuzumab Emtansine in Japanese Patients with HER2-Positive Advanced Breast Cancer. Watanabe, J., Ito, Y., Saeki, T., et al.[2022]

Trastuzumab emtansine (T-DM1) is an effective treatment for HER2-positive breast cancer, showing significant improvements in progression-free survival and overall survival in patients who have previously undergone anti-HER2 therapies, as demonstrated in phase III trials EMILIA and TR3RESA.

The safe dosing range for T-DM1 has been established at 3.6 mg/kg every 3 weeks, and it has a favorable safety and tolerability profile, making it a promising option for patients with advanced breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of HER2 positive advanced breast cancer with T-DM1: A review of the literature. Martínez, MT., Pérez-Fidalgo, JA., Martín-Martorell, P., et al.[2022]

The KAMILLA study, involving 2002 patients with HER2-positive advanced breast cancer, demonstrated that trastuzumab emtansine (T-DM1) is a safe and tolerable treatment, with 93% of patients experiencing adverse events, primarily mild to moderate in severity.

The study reported a median progression-free survival of 6.9 months and a median overall survival of 27.2 months, indicating that T-DM1 is an effective option for patients who have previously undergone multiple lines of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of trastuzumab emtansine (T-DM1) in patients with HER2-positive advanced breast cancer: Primary results from the KAMILLA study cohort 1. Montemurro, F., Ellis, P., Anton, A., et al.[2020]

Trastuzumab emtansine (T-DM1) has shown a favorable safety profile in 884 patients with HER2-positive metastatic breast cancer, with most adverse events being manageable and asymptomatic, such as fatigue and nausea.

The treatment demonstrated superior efficacy compared to standard therapies in previous studies, making T-DM1 a promising option for further exploration in other breast cancer settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab emtansine in human epidermal growth factor receptor 2-positive metastatic breast cancer: an integrated safety analysis. Diéras, V., Harbeck, N., Budd, GT., et al.[2019]

In a study of 110 patients with HER2-positive metastatic breast cancer who had previously received multiple treatments, the antibody-drug conjugate trastuzumab emtansine (T-DM1) showed an overall response rate of 34.5% and a clinical benefit rate of 48.2%, indicating its effectiveness as a treatment option.

T-DM1 was well tolerated, with most side effects being mild (grades 1 to 2), and the most common severe side effects included thrombocytopenia and fatigue, suggesting a favorable safety profile for patients who have exhausted other HER2-targeted therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of trastuzumab emtansine in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer who were previously treated with trastuzumab, lapatinib, an anthracycline, a taxane, and capecitabine. Krop, IE., LoRusso, P., Miller, KD., 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]

In a phase 3 trial involving 1486 patients with HER2-positive early breast cancer, adjuvant treatment with trastuzumab emtansine (T-DM1) significantly reduced the risk of invasive disease or death by 50% compared to trastuzumab alone, with 12.2% of patients in the T-DM1 group experiencing these events versus 22.2% in the trastuzumab group.

The estimated 3-year invasive disease-free survival rate was 88.3% for the T-DM1 group compared to 77.0% for the trastuzumab group, indicating that T-DM1 is more effective in preventing recurrence after neoadjuvant therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer. von Minckwitz, G., Huang, CS., Mano, MS., et al.[2022]

Citations

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Real-world efficacy and safety of trastuzumab deruxtecan ... Interpretation: In this real-world study, T-DXd was more effective than T-DM1 as a second-line treatment and tucatinib as a third-line treatment, in line with ...

2. facingourrisk.org facingourrisk.org/XRAY/combining-anti-HER2-drugs-improves-outcomes

Combining two anti-HER2 drugs improves outcomes ... Previously, the HER2CLIMB trial found that adding Tukysa to Herceptin and chemotherapy significantly improved both the time until cancer came ...

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Real-World Data Support Tucatinib-Based Treatment in ... Tucatinib-based treatments showed effectiveness in HER2-positive metastatic breast cancer, including brain metastases and post-T-DXd treatment ...

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Tucatinib plus T-DM1 effective against HER2-positive ... Tucatinib given in combination with trastuzumab emtansine is effective as a second-line treatment for locally advanced or metastatic HER2-positive breast cancer ...

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NCT01983501 | A Study of Tucatinib (ONT-380) Combined ... This is a Phase 1b, open-label study of tucatinib (ONT-380) given in combination with ado-trastuzumab emtansine (T-DM1) to patients with HER2+ breast cancer.

6. sciencedirect.com sciencedirect.com/science/article/pii/S2666776225002479

Real-world efficacy and safety of trastuzumab deruxtecan ... Clinical trials have proven that trastuzumab deruxtecan (T-DXd) and tucatinib are key therapies for the treatment of HER2-positive metastatic breast cancer in ...

7. nature.com nature.com/articles/s41591-024-03462-0

Tucatinib and trastuzumab in HER2-mutated metastatic ... An open-label, phase 2 basket study evaluating tucatinib, a HER2-targeted tyrosine kinase inhibitor, in combination with trastuzumab in patients with HER2- ...