Tucatinib+Trastuzumab+Eribulin in HER2+ MBC

NCT05458674 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 02AB21-TucErBit
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 6

Brief Summary

The purpose of this study is to evaluate the safety and efficacy of the three-drug combination of tucatinib, trastuzumab, and eribulin in patients with de novo and recurrent unresectable metastatic HER-2/neu positive breast cancer as assessed by ORR, PFS and OS after prior treatment with a taxane, trastuzumab, and T-DM1.

Conditions

Breast Cancer; Pretreated Unresectable Locally Advanced or Metastatic HER2+ Breast Cancer

Keywords

Pretreated Unresectable locally advanced or metastatic HER2+ breast cancer

Outcome Measures

Primary Outcomes (2)

• To assess the safety and tolerability of tucatinib in combination with eribulin and trastuzumab in patients with unresectable or recurrent metastatic HER2+ breast cancer who have had prior treatment with trastuzumab, and trastuzumab deruxtecan.

  Incidence of adverse events and serious adverse events. Rate of grade 3 -4 toxicity, incidence of dose limiting toxicities, incidence of dose holding, dose reductions, and discontinuations of any and/or all of the three treatment agents. Incidence of cardiac and pulmonary complications.

  2 years

• Evaluate the relative toxicity/tolerability of these therapeutic agents when used in combination in this patient cohort

  Rate of grade 3 -4 toxicity, incidence of dose limiting toxicities, incidence of dose holding, dose reductions, and discontinuations of any and/or all of the three treatment agents

  2 years

Secondary Outcomes (4)

• Evaluate efficacy against HER2 + metastatic breast cancer

  2 years

• Evaluate efficacy against CNS disease

  2 years

• Efficacy in patients who have had prior tucatinib

  2 years

• Efficacy in treating CNS disease

  2 years

Study Arms (1)

Tucatinib/Eribulin/Trastuzumab

EXPERIMENTAL

* The initial dose of trastuzumab will be given as a loading dose of 8 mg/kg intravenously (IV), unless trastuzumab was administered within the prior 4 weeks, then the initial dose of trastuzumab will be administered at a dose of 6 mg/kg. Each trastuzumab dose is given once every 21 days, except in specific circumstances where it may be given weekly to compensate for modifications in treatment schedule * Tucatinib 300 mg orally twice daily (PO BID) every day (Days 1-21) of each 21-day cycle using a modified schedule of events. Subcutaneous trastuzumab is given only once every three weeks as there is no allowance for weekly dosing. * Eribulin will be given at a dose of 1.1 mg/M2 intravenously over a 2-5 minute period on days 1 and 8 of each 21-day cycle.

Drug: Tucatinib; Drug: Eribulin; Drug: Trastuzumab

Interventions

Tucatinib DRUG

taken orally

Also known as: TUKYSA

Tucatinib/Eribulin/Trastuzumab

Eribulin DRUG

taknen intravenously

Also known as: HALAVEN

Tucatinib/Eribulin/Trastuzumab

Trastuzumab DRUG

taken intravenously

Also known as: HERCEPTIN

Tucatinib/Eribulin/Trastuzumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed HER2+ breast carcinoma, with HER2+ defined by in situ hybridization (ISH) or fluorescence in situ hybridization (FISH) or immunohistochemistry (IHC)
• Have received previous treatment with trastuzumab deruxtecan in the metastatic setting or have recurred within 6 months of receiving this treatment in the adjuvant or neoadjuvant setting. Prior taxane, capecitabine and T-DM1 are not required. Prior tucatinib therapy is allowed. Patients for whom Trastuzumab is contraindicated are not permitted. Have progression of unresectable locally advanced or metastatic breast cancer after last systemic therapy (as confirmed by site investigator),or be intolerant of last systemic therapy.
• Have measurable or non-measurable disease assessable by RECIST 1.1
• Be at least 18 years of age at time of consent.
• Have Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0,1 or 2
• Have a life expectancy of at least 6 months, in the opinion of the site investigator.
• Have adequate hepatic function as defined by the following:
• Total bilirubin ≤1.5 X upper limit of normal (ULN), except for patients with known Gilbert's disease, who may enroll if the conjugated bilirubin is ≤1.5 X ULN
• Transaminases \[aspartate aminotransferase/serum glutamic oxaloacetic transaminase (AST/SGOT) and alanine aminotransferase/serum glutamic pyruvic transaminase (ALT/SGPT)\] ≤ 2.5 X ULN (≤ 5 X ULN if liver metastases are present)
• Have adequate baseline hematologic parameters as defined by:
• Absolute neutrophil count (ANC) ≥ 1.5 x 103/µL
• Platelet count ≥ 100 x 103/µL; patients with stable platelet count from 75- 100 x 103/µL may be included with approval from medical monitor,
• Hemoglobin ≥ 9 g/dL
• In patients transfused before study entry, transfusion must be ≥ 14 days prior to start of therapy to establish adequate hematologic parameters independent from transfusion support,
• Have creatinine clearance ≥ 50 mL/min as calculated per institutional guidelines or, in patients ≤ 45 kg in weight, a serum creatinine within institutional normal limits,

You may not qualify if:

• Have previously been treated with eribulin for metastatic disease (except in cases where eribulin was given for ≤ 21 days and was discontinued for reasons other than disease progression or severe toxicity)
• History of exposure to the following cumulative doses of anthracyclines:
• Doxorubicin \> 360 mg/m2
• Epirubicin \> 720 mg/m2
• Mitoxantrone \> 120 mg/m2
• Idarubicin \> 90 mg/m2
• Liposomal doxorubicin (e.g. Doxil, Caelyx, Myocet) \> 550 mg/m2
• History of allergic reactions to trastuzumab, eribulin, or compounds chemically or biologically similar to tucatinib, except for Grade 1 or 2 infusion related reactions to trastuzumab that were successfully managed, or known allergy to one of the excipients in the study drugs
• Have received treatment with any systemic anti-cancer therapy (including hormonal therapy), non-CNS radiation, or experimental agent ≤ 3 weeks of first dose of study treatment or are currently participating in another interventional clinical trial. An exception for the washout of hormonal therapies is gonadotropin releasing hormone (GnRH) agonists used for ovarian suppression in premenopausal women, which are permitted concomitant medications.
• Have any toxicity related to prior cancer therapies that has not resolved to ≤ Grade 1, with the following exceptions:
• alopecia and neuropathy, which must have resolved to ≤ Grade 2; and
• congestive heart failure (CHF), which must have been ≤ Grade 1 in severity at the time of occurrence, and must have resolved completely.
• anemia, which must have resolved to ≤ Grade 2
• Have clinically significant cardiopulmonary disease such as:
• ventricular arrhythmia requiring therapy,

Sponsors & Collaborators

• Criterium, Inc.: lead

Study Sites (6)

University of Colorado

Aurora, Colorado, 80045, United States

RECRUITING

George Washington Medical Faculty Associates

Washington D.C., District of Columbia, 20037, United States

RECRUITING

New Mexico Cancer Care Alliance

Albuquerque, New Mexico, 87131, United States

RECRUITING

Swedish Cancer Institute

Issaquah, Washington, 98029, United States

RECRUITING

Cancer Care Northwest

Spokane Valley, Washington, 99216, United States

RECRUITING

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, 53792, United States

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

tucatinib; eribulin; Trastuzumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Hank Kaplan, MD

  henry.kaplan@swedish.org

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Bebi Yassin-Rajkumar

CONTACT

6138511370; byassin-rajkumar@criteriuminc.com

James Zemer

CONTACT

585-943-6551; jzemer@criteriuminc.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 27, 2022
• First Posted: July 14, 2022
• Study Start: January 30, 2024
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): August 1, 2027
• Last Updated: January 12, 2026

Record last verified: 2026-01

Locations

US (6)