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Breast CancerPhase 2NCT05458674

Tucatinib+Trastuzumab+Eribulin in HER2+ MBC

A Phase 2 study testing Tucatinib, Eribulin and Trastuzumab in people with Breast Cancer and Pretreated Unresectable Locally Advanced or Metastatic HER2+ Breast Cancer, run by Criterium, Inc. at 6 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Tucatinib, Eribulin and Trastuzumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
17 participants
Where
6 sitesUnited States
Study dates
30 Jan 2024to 1 Aug 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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,
  • International normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤ 1.5 X ULN unless on medication known to alter INR and aPTT. (Note: Warfarin and other coumarin derivatives are prohibited.)
  • Have left ventricular ejection fraction (LVEF) ≥ 50% as assessed by echocardiogram (ECHO) or multiple-gated acquisition scan (MUGA) documented within 4 weeks prior to first dose of study treatment.
  • If female of childbearing potential, must have a negative result of serum or urine pregnancy test performed within 7 days prior to first dose of study treatment. A woman is considered of childbearing potential, i.e. fertile, following menarche and until becoming post- menopausal unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause.
  • NOTE: Postmenopausal patients with known β-HCG secreting tumors may be eligible when β-HCG-based urine or serum pregnancy tests yield false positive if they meet the definition of postmenopausal state and have a negative uterine ultrasound
  • Women of childbearing potential (as defined above) and men with partners of childbearing potential must agree to use a highly effective birth control method, i.e., methods that achieve a failure rate of less than 1% per year when used consistently and correctly. Such methods include: combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, or transdermal); progestogen- only hormonal contraception associated with inhibition of ovulation (oral, injectable, or implantable); intrauterine device; intrauterine hormone-releasing system; bilateral tubal occlusion/ligation; vasectomized partner; or sexual abstinence. Male patients with partners of childbearing potential must use barrier contraception. All study patients should practice effective contraception, as described above, starting from the signing of informed consent until 7 months after the last dose of study medication or investigational medicinal product.
  • Patient must provide signed informed consent per a consent document that has been approved by an institutional review board or independent ethics committee (IRB/IEC) prior to initiation of any study-related tests or procedures that are not part of standard-of-care for the patient's disease.
  • Patients must be willing and able to comply with study procedures.
  • CNS Inclusion - Based on screening contrast brain magnetic resonance imaging (MRI), patients must have one of the following:
  • No evidence of brain metastases
  • Untreated brain metastases not needing immediate local therapy. For patients with untreated CNS lesions > 2.0 cm on screening contrast brain MRI, discussion with and approval from the medical monitor is required prior to enrollment,
  • Previously treated brain metastases a. Brain metastases previously treated with local therapy may either be stable since treatment or may have progressed since prior local CNS therapy, provided that there is no clinical indication for immediate re-treatment with local therapy in the opinion of the site investigator, b. Patients treated with CNS local therapy for newly identified lesions found on contrast brain MRI performed during screening for this study may be eligible to enroll if all of the following criteria are met: i. Time since whole brain radiation therapy (WBRT) is ≥ 21 days prior to first dose of study treatment, time since stereotactic radiosurgery (SRS) is ≥ 7 days prior to first dose of study treatment, or time since surgical resection is ≥ 28 days, ii. Other sites of disease assessable by RECIST 1.1 are present, iii. Relevant records of any CNS treatment must be available to allow for classification of target and non-target lesions

Who cannot join

  • 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
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  • 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,
  • uncontrolled hypertension (defined as persistent systolic blood pressure > 150 mm Hg and/or diastolic blood pressure > 100 mm Hg on antihypertensive medications)
  • any history of symptomatic CHF
  • severe dyspnea at rest (CTCAE Grade 3 or above) due to complications of advanced malignancy
  • hypoxia requiring supplementary oxygen therapy except when oxygen therapy is needed only for obstructive sleep apnea.
  • Presence of Grade 2 or greater QTc prolongation on screening ECG.
  • conditions potentially resulting in drug-induced prolongation of the QT interval or torsade de pointes:
  • Congenital or acquired long QT syndrome. ii. Family history of sudden death iii. History of previous drug induced QT prolongation iv. Current use of medications with known and accepted associated risk of QT prolongation
  • Have known myocardial infarction or unstable angina within 6 months prior to first dose of study treatment.
  • Have chronic active Hepatitis B or Hepatitis C or have other known chronic liver disease.
  • Are known to be positive for human immunodeficiency virus (HIV)
  • Are pregnant, breastfeeding, or planning a pregnancy.
  • Require therapy with warfarin or other coumarin derivatives (non-coumarin anticoagulants are allowed)
  • Have inability to swallow pills or significant gastrointestinal disease which would preclude the adequate oral absorption of medications.
  • Use of a strong CYP3A4 or CYP2C8 inhibitor within 5 half-lives of the inhibitor, or use of a strong CYP3A4 or CYP2C8 inducer within 5 days prior to first dose of study treatment
  • Unable for any reason to undergo contrast MRI of the brain.
  • Have any other medical, social, or psychosocial factors that, in the opinion of the investigator, could impact safety or compliance with study procedures.
  • Have evidence within 2 years of the start of study treatment of another malignancy that required systemic treatment.
  • CNS Exclusion - Based on screening brain MRI, patients must not have any of the following:
  • Any untreated brain lesions > 2.0 cm in size, unless discussed with medical monitor and approval for enrollment is given.
  • Ongoing use of systemic corticosteroids for control of symptoms of brain metastases at a total daily dose of > 2 mg of dexamethasone (or equivalent). However, patients on a chronic stable may be eligible with discussion and approval by the medical monitor.
  • Any brain lesion thought to require immediate local therapy, including (but not limited to) a lesion in an anatomic site where increase in size or possible treatment-related edema may pose risk to patient (e.g., brain stem lesions). Patients who undergo local treatment for such lesions identified by screening contrast brain MRI may still be eligible for the study based on criteria described under CNS inclusion criteria 19b.
  • Have poorly controlled (> 1/week) generalized or complex partial seizures, or manifest neurologic progression due to brain metastases notwithstanding CNS-directed therapy

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

United States6 sites

  • New Mexico Cancer Care Alliance

    Albuquerque, New Mexico, 87131

  • University of Colorado

    Aurora, Colorado, 80045

  • Swedish Cancer Institute

    Issaquah, Washington, 98029

  • University of Wisconsin Carbone Cancer Center

    Madison, Wisconsin, 53792

  • Cancer Care Northwest

    Spokane Valley, Washington, 99216

  • George Washington Medical Faculty Associates

    Washington D.C., District of Columbia, 20037

Other trials in United States

About this study

Official title: A Phase II Study of the Safety, Tolerability and Antitumor Activity of Tucatinib in Combination With Eribulin and Trastuzumab in Patients With Pretreated Unresectable Locally Advanced or Metastatic HER2+ Breast Cancer

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.

Read the detailed description

In view of the potency of tucatinib for the treatment of brain metastases and its modest toxicity, it is important to evaluate the combination of this drug with other established anti-HER2 therapies. There remains a need to evaluate the efficacy of tucatinib with additional active agents in this area. Given the demonstrated activity of eribulin in metastatic breast cancer in general and in her2 positive disease combined with trastuzumab in particular, this study proposes to evaluate the safety and efficacy of the three-drug combination of eribulin, trastuzumab, and tucatinib. It is also important to ascertain the activity of this combination in patients who have previously received tucatinib, as little is known about whether resistance to tucatinib plus one chemotherapy drug confers resistance to tucatinib with a different partner drug.

Being tested
Tucatinib, Eribulin, Trastuzumab
Keywords
Pretreated Unresectable locally advanced or metastatic HER2+ breast cancer
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TucatinibDrug

    Also called TUKYSA

    taken orally

  • EribulinDrug

    Also called HALAVEN

    taknen intravenously

  • TrastuzumabDrug

    Also called HERCEPTIN

    taken intravenously

Study groups in NCT05458674
Study groupRoleWhat they receive
Tucatinib/Eribulin/TrastuzumabExperimental* 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.
Receives: Drug: Tucatinib; Drug: Eribulin; Drug: Trastuzumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 2 years

  2. 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

    Measured: 2 years

Secondary outcomes (4)

  1. Evaluate efficacy against HER2 + metastatic breast cancer

    Overall response rate (ORR) and progression-free survival (PFS) will be assessed per RECIST 1.1 criteria

    Measured: 2 years

  2. Evaluate efficacy against CNS disease

    progressive disease will be assessed per RANDO-BM criteria

    Measured: 2 years

  3. Efficacy in patients who have had prior tucatinib

    Assessed per Overall survival and Progression Free survival in patients who have received prior tucatinib therapy

    Measured: 2 years

  4. Efficacy in treating CNS disease

    Assessed per Overall survival and Progression Free survival in patients with CNS disease

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Jul 2022
  2. Study start30 Jan 2024
  3. Primary completion1 Jun 2027 (estimated)
  4. Study completion1 Aug 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
17 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05458674
Sponsor's protocol ID
02AB21-TucErBit
Status last verified
Mar 2026
First submitted
27 Jun 2022
Last updated
10 Jul 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Tucatinib, Eribulin and Trastuzumab in people with Breast Cancer and Pretreated Unresectable Locally Advanced or Metastatic HER2+ Breast Cancer, run by Criterium, Inc. at 6 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 26 inclusion and 37 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 10 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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. (time frame: 2 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05458674.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jul 2026.

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