Tucatinib Combination for Breast Cancer

(BRIDGET Trial)

Recruiting in Palo Alto (17 mi)

+8 other locations

Overseen by Sarah Sammons, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Sarah Sammons, MD

Must be taking: Trastuzumab, Pertuzumab, T-DM1, Tucatinib

Must not be taking: Lapatinib, Neratinib, Afatinib, others

Disqualifiers: Cardiopulmonary disease, Acute infection, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

Patients with advanced HER2+ breast cancer on maintenance trastuzumab/pertuzumab or T-DM1 with 1st or 2nd intracranial disease event (brain metastases) and stable extracranial disease will be enrolled. They will receive local therapy with stereotactic radiosurgery ± surgical resection if indicated followed by enrollment. Patients will continue standard of care trastuzumab/pertuzumab or T-DM1 with the addition of tucatinib. Hormone receptor positive patients requiring endocrine therapy should continue. Study treatment will continue until disease progression or intolerable side effects. Patients on trial with extracranial disease progression with stable intracranial disease should continue tucatinib into next line of therapy.

Will I have to stop taking my current medications?

The trial does not require you to stop taking your current medications. In fact, if you are on trastuzumab/pertuzumab, T-DM1, or need endocrine therapy, you should continue them while participating in the study.

What data supports the effectiveness of the drug combination including Tucatinib, Pertuzumab, and Trastuzumab Emtansine for breast cancer?

Research shows that Trastuzumab Emtansine (T-DM1) combined with Pertuzumab is effective for treating HER2-positive advanced breast cancer, offering similar progression-free survival and better tolerability compared to other treatments. Additionally, combining T-DM1 with Pertuzumab has shown enhanced antitumor activity in preclinical studies.

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Is the combination of tucatinib and other drugs safe for treating breast cancer?

The combination of trastuzumab emtansine (T-DM1) with or without pertuzumab has been studied for safety in patients with HER2-positive advanced breast cancer. These studies showed that T-DM1 generally has a better safety profile compared to some other treatments, with fewer severe side effects. However, like all treatments, it can still cause some adverse effects, which were carefully monitored in clinical trials.

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What makes the Tucatinib Combination for Breast Cancer drug unique?

The Tucatinib Combination for Breast Cancer is unique because it includes tucatinib, an oral drug that specifically targets HER2, a protein that promotes the growth of cancer cells. This combination is being developed as a novel option for patients whose cancer has progressed after standard treatments like trastuzumab, pertuzumab, and T-DM1, offering a new approach when other options are limited.

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Eligibility Criteria

This trial is for adults over 18 with advanced HER2+ breast cancer who have had brain metastases treated and stable disease elsewhere. They must be on specific therapies (trastuzumab/pertuzumab or T-DM1), have good organ function, and not be pregnant or breastfeeding. Contraception use is required for participants of childbearing potential.

Inclusion Criteria

My breast cancer has spread to my brain (Stage IV).

My cancer is stable or I have no cancer spread outside the brain.

I am able to get out of my bed or chair and move around.

Exclusion Criteria

You cannot have ongoing use of certain medications for brain issues, specific brain conditions, poorly controlled seizures, certain medical treatments, active infections, or recent use of experimental drugs.

I do not have an active infection needing strong medication.

I haven't taken strong CYP2C8 or CYP3A4 drugs recently.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Local Therapy

Participants receive local therapy with stereotactic radiosurgery ± surgical resection if indicated

3 weeks

1 visit (in-person)

Treatment

Participants continue standard of care treatment with trastuzumab/pertuzumab or T-DM1 with the addition of tucatinib

Until disease progression or intolerable side effects

Every 3 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

Participant Groups

The study tests adding tucatinib to standard care (trastuzumab/pertuzumab or T-DM1) after local therapy like surgery or radiosurgery in patients with HER2+ breast cancer that has spread to the brain. The goal is to prevent further brain metastases and manage the disease.

Group I: Experimental Group Experimental Treatment 4 Interventions

Trastuzumab/pertuzumab + tucatinib or T-DM1 + tucatinib 300mg of tucatinib taken orally twice a day. Taken on Days 1-21 of a 21 Day cycle (3 Weeks). Trastuzumab/Biosimilar administered per current package insert based on site standard of care guidelines Pertuzumab or Biosimilar administered per current package insert based on site standard of care guidelines Trastuzumab Emtansine (T-DM1) administered per current package insert based on site standard of care guidelines

Pertuzumab is already approved in European Union, United States, Canada, Japan for the following indications:

🇪🇺 Approved in European Union as Perjeta for:

• Early breast cancer
• Metastatic breast cancer

🇺🇸 Approved in United States as Perjeta for:

• Early breast cancer
• Metastatic breast cancer

🇨🇦 Approved in Canada as Perjeta for:

• Early breast cancer
• Metastatic breast cancer

🇯🇵 Approved in Japan as Perjeta for:

• Early breast cancer
• Metastatic breast cancer

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

University of California San Francisco San Francisco, CA

Washington University in St. Louis St. Louis, MO

Ohio State University Comprehensive Cancer Center Columbus, OH

Duke University Medical Center Durham, NC

More Trial Locations

Who Is Running the Clinical Trial?

Sarah Sammons, MD Lead Sponsor

Carey Anders, M.D. Lead Sponsor

Pfizer Industry Sponsor

Seagen Inc. Industry Sponsor

References

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

Safety and efficacy of the addition of pertuzumab to T-DM1 ± taxane in patients with HER2-positive, locally advanced or metastatic breast cancer: a pooled analysis. [2022] The aim of this review was to systematically evaluate the safety and efficacy of the addition of pertuzumab to trastuzumab emtansine (T-DM1) ± taxane in patients with human epidermal growth factor receptor 2 (HER2)-positive, locally advanced breast cancer (LABC) or metastatic breast cancer (MBC).

2. England pubmed.ncbi.nlm.nih.gov

Trastuzumab emtansine (T-DM1) plus docetaxel with or without pertuzumab in patients with HER2-positive locally advanced or metastatic breast cancer: results from a phase Ib/IIa study. [2022] Trastuzumab emtansine (T-DM1) exhibited enhanced antitumor activity when combined with docetaxel or pertuzumab in preclinical studies. This phase Ib/IIa study assessed the feasibility of T-DM1 + docetaxel in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) and T-DM1 + docetaxel ± pertuzumab in patients with HER2-positive locally advanced breast cancer (LABC).

3. 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] 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.

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

Trastuzumab emtansine with or without pertuzumab versus trastuzumab with taxane for human epidermal growth factor receptor 2-positive advanced breast cancer: Final results from MARIANNE. [2020] In the phase 3 MARIANNE trial, trastuzumab emtansine (T-DM1) with or without pertuzumab showed noninferior progression-free survival and better tolerability than trastuzumab plus a taxane (HT) for the first-line treatment of human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer. This article reports the final descriptive overall survival (OS) analysis, updated safety data, and additional patient-reported outcomes and biomarker analyses.

5. Germany pubmed.ncbi.nlm.nih.gov

Combination efficacy of pertuzumab and trastuzumab for trastuzumab emtansine-resistant cells exhibiting attenuated lysosomal trafficking or efflux pumps upregulation. [2021] Trastuzumab emtansine (T-DM1) is the standard treatment in the current second-line therapy of human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. However, a useful therapy after T-DM1 resistance has not been established. In this study, we established two different HER2-positive T-DM1-resistant cancer cells and evaluated the antitumor effect of trastuzumab in combination with pertuzumab (TRAS + PER).

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

Trastuzumab emtansine in human epidermal growth factor receptor 2-positive metastatic breast cancer: an integrated safety analysis. [2019] The antibody-drug conjugate trastuzumab emtansine (T-DM1) combines the cytotoxic activity of DM1 with the human epidermal growth factor receptor 2 (HER2) -targeted, antitumor properties of trastuzumab. T-DM1 has shown activity in phase I and II single-arm studies in patients with pretreated HER2-positive metastatic breast cancer (MBC) and has demonstrated superior efficacy and improved tolerability versus standard MBC treatments in randomized phase II and III studies. This analysis, combining available data from all single-agent T-DM1 studies to date, was conducted to better define the T-DM1 safety profile.

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

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.

8. Japan pubmed.ncbi.nlm.nih.gov

Clinical benefit of treatment after trastuzumab emtansine for HER2-positive metastatic breast cancer: a real-world multi-centre cohort study in Japan (WJOG12519B). [2021] Trastuzumab emtansine (T-DM1) treatment for human epidermal growth factor receptor-2 (HER2)-positive metastatic breast cancer after taxane with trastuzumab and pertuzumab is standard therapy. However, treatment strategies beyond T-DM1 are still in development with insufficient evidence of their effectiveness. Here, we aimed to evaluate real-world treatment choice and efficacy of treatments after T-DM1 for HER2-positive metastatic breast cancer.