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Metastatic Solid TumorPhase 2NCT05673928

A Phase II Study of Tucatinib and Ado-trastuzumab Emtansine (T-DM1) in Patients With HER2-positive Metastatic Solid Tumors and Metastases to Brain (TUCATEMEB)

A Phase 2 study testing Trastuzumab emtansine and Tucatinib in people with Metastatic Solid Tumor and Brain Metastases, run by M.D. Anderson Cancer Center at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

To learn if the study drugs, tucatinib and adotrastuzumab emtansine (T-DM1), can help to control solid tumors that have spread to the brain. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Solid Tumor, Brain Metastases
What is being tested?
Trastuzumab emtansine and Tucatinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
1 siteUnited States
Study dates
16 May 2023to 1 Mar 2029
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-positive metastatic solid tumor. HER2 positivity defined as HER2 overexpression by immunohistochemistry (IHC) 3+ or 2+ and fluorescence in situ hybridization (FISH) positive and/or HER2 amplification by in situ hybridization (ISH) or next generation sequencing (NGS) and/or activating ERBB2 mutation(s) (verified by MDACC Precision Oncology Decision Support).
  • Patients must have one of the following on the screening brain MRI:
  • Untreated brain metastases not requiring immediate local CNS therapy
  • Previously treated brain metastases with progression of previous lesions or new lesions, but not requiring immediate local CNS therapy
  • At least one measurable untreated brain lesion ≥0.5 cm and <3.0 cm in the longest axis
  • Prior SRS radiosurgery (must be completed within 7 days of study treatment initiation) is allowed as long as the previous treatment volume does not overlap with the current targets.
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  • Measurable (per the RECIST v1.1) or evaluable extracranial disease.
  • Prior treatment with HER2-targeted treatments such as trastuzumab, pertuzumab, T-DM1, neratinib, lapatinib, or tucatinib is allowed, but not required. Patients with breast and gastric cancer must have received at least 1 line of HER2 targeted treatment.
  • Age ≥18 years at the time of consent.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 (Appendix B).
  • Life expectancy ≥3 months, in the opinion of the investigator.
  • Adequate hematological and end-organ function, defined by the following laboratory test results, obtained within 28 days prior to study treatment initiation:
  • Absolute neutrophil count ≥1,200/μL
  • Platelet count ≥100,000/μL
  • Hemoglobin ≥9g/dL
  • Total bilirubin ≤1.5 × upper limit of normal (ULN), except for patients with known Gilbert's disease, who may enroll if conjugated bilirubin is ≤1.5 × ULN
  • Transaminases (AST/ALT) ≤1.5 × ULN (≤5 × ULN if liver metastases are present)
  • Creatinine level <1.5 x ULN or estimated glomerular filtration rate (GFR) ≥50 mL/min/1.73 m2 using the Modification of Diet in Renal Disease (MDRD) study equation as applicable.
  • International normalized ratio (INR) and partial thromboplastin time (PTT)/activated partial thromboplastin time (aPTT) ≤1.5 × ULN, unless on medication known to alter INR and PTT/aPTT. Proprietary Information of MD Anderson Protocol 2021-0899 v.5.0,04/24/2023 28
  • LVEF ≥50% as assessed by echocardiogram (ECHO) or multi-gated acquisition (MUGA) scan documented within 3weeks prior to study treatment initiation.
  • For patients of childbearing potential, as defined in Section 4.3, the following stipulations apply:
  • Must have a negative serum or urine pregnancy test (minimum sensitivity of 25 mIU/mL or equivalent units of beta-human chorionic gonadotropin [β-hCG]) result within 3 days prior to study treatment initiation. A patient with a false positive result and documented verification that the patient is not pregnant will be eligible.
  • Must agree not to try to become pregnant during the study and for at least 7 months after the final dose of study treatment
  • Must agree not to breastfeed or donate ova starting at the time of informed consent and continuing through the study and for 7 months after the final dose of study treatment
  • If sexually active in a way that could lead to pregnancy, must consistently use highly effective methods of birth control (i.e., methods that achieve a failure rate of <1% per year when used consistently and correctly) starting at the time of informed consent and continuing throughout the study and for at least 7 months after the final dose of study treatment.
  • Highly effective methods of birth control include:
  • Intrauterine device ii. Bilateral tubal occlusion/ligation iii. Vasectomized partner iv. Sexual abstinence when it is the preferred and usual lifestyle choice of the patient.
  • For patients who can father children, the following stipulations apply:
  • Must agree not to donate sperm starting at the time of informed consent and continuing throughout the study and for at least 7 months after the final dose of study treatment
  • If sexually active with a person of childbearing potential in a way that could lead to pregnancy, must consistently use a barrier method of birth control starting at the time of informed consent and continuing throughout the study and for at least 7 months after the final dose of study treatment
  • If sexually active with a person who is pregnant or breastfeeding, must consistently use a barrier method of birth control starting at the time of informed consent and continuing throughout the study and for at least 7 months after the final dose of study treatment.
  • The patient must provide written informed consent.
  • Must be willing to undergo biopsy as required by the study, if clinically considered safe and feasible by the investigator.

Who cannot join

  • Patients must not have any of the following on the screening brain MRI:
  • Any untreated brain lesions >3.0 cm in size
  • 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 the patient (e.g., brainstem lesions). Patients who undergo local treatment for such lesions may still be eligible for the study based on inclusion criteria #2.
  • Ongoing use of systemic corticosteroids for control of symptoms of brain metastases at a total daily dose of >4 mg of dexamethasone (or equivalent).
  • Poorly controlled (>1/week) generalized or complex partial seizures, or manifestation of neurologic progression due to brain metastases notwithstanding CNS-directed therapy.
  • History of allergic reactions to trastuzumab or compounds chemically or biologically similar to tucatinib, except for Grade 1 or 2 IRRs to trastuzumab that were successfully managed, or known allergy to any of the excipients in the study drugs.
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  • Treatment with any systemic anticancer therapy or investigational agent within 5 half-lives (of the drug) or within 21 days (whichever is shorter ) prior to study treatment initiation.
  • Any toxicity related to prior cancer therapies that has not resolved to ≤ Grade 1, with the following exceptions:
  • Alopecia;
  • Neuropathy, which must have resolved to ≤ Grade 2;
  • Congestive heart failure (CHF), which must have been ≤ Grade 1 in severity at the time of occurrence and must have resolved completely.
  • Clinically significant cardiopulmonary disease such as:
  • Ventricular arrhythmia requiring therapy
  • Symptomatic hypertension or uncontrolled asymptomatic hypertension as determined by the investigator
  • Any history of symptomatic CHF, left ventricular systolic dysfunction, or decrease in LVEF
  • Severe dyspnea at rest (National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] ≥ Grade 3) due to complications of advanced malignancy or hypoxia requiring supplementary oxygen therapy
  • Grade 2 or greater corrected QT interval (QTc) prolongation on screening electrocardiogram (ECG).
  • Known myocardial infarction or unstable angina within 6 months prior to study treatment initiation.
  • Unable for any reason to undergo contrast MRI of the brain.
  • Have used a strong cytochrome P450 (CYP)2C8 inhibitor within 5 half-lives of the inhibitor, or a strong CYP3A4 or CYP2C8 inducer within 5 days prior to study treatment initiation. Concomitant use of strong CYP3A4 inducers or CYP2C8 inducers or inhibitors is also prohibited during study treatment and for 2 weeks after discontinuation of study treatment. Use Proprietary Information of MD Anderson of sensitive CYP3A substrates should be avoided 2 weeks prior to study treatment initiation and during study treatment.
  • Known carrier of hepatitis B or hepatitis C virus or has other known chronic liver disease.
  • Known positive human immunodeficiency virus status.
  • Patients who are pregnant, breastfeeding, or planning to become pregnant from the time of informed consent until 7 months after the last dose of study treatment.
  • Unable to swallow pills or has significant GI disease that would preclude adequate oral absorption of medication.
  • Other medical, social, or psychosocial factors that, in the opinion of the investigator, could impact patient safety or compliance with study procedures.
  • Evidence within 1 year of the start of study treatment of another malignancy that required systemic treatment.
  • Patients who are eligible for the HER2CLIMB-02 study (NCT03975647) and they can be enrolled in that study.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Ecaterina Dumbrava, MD contact

713-563-1930

eeileana@mdanderson.org

United States1 site, 1 recruiting

  • M D Anderson Cancer Center

    Houston, Texas, 77030

    Ecaterina Dumbrava, MD, 713-563-1930, eeileana@mdanderson.org

    Ecaterina Dumbrava, MD

    Recruiting

Other trials in United States

About this study

To learn if the study drugs, tucatinib and adotrastuzumab emtansine (T-DM1), can help to control solid tumors that have spread to the brain.

Read the detailed description

Primary Objectives:

● To determine the intracranial antitumor activity of the tucatinib and ado-trastuzumab emtansine (T- bination per the modified Response Evaluation Criteria in Solid Tumors (mRECIST) in patients with huma

Key Secondary Objectives:

  • To determine the intracranial antitumor activity of the tucatinib and T-DM1 combination per the Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria in patients with HER2-positive metastatic solid tumors and brain metastases.
  • To evaluate the duration of intracranial response of the tucatinib and T-DM1 combination in patients with HER2-positive metastatic solid tumors and brain metastases.

Other Secondary Objectives:

  • To evaluate the safety and tolerability of the tucatinib and T-DM1 combination in patients with HER2-positive metastatic solid tumors and brain metastases.
  • To evaluate the systemic antitumor activity of the tucatinib and T-DM1 combination per the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 in patients with HER2-positive metastatic solid tumors and brain metastases.
  • To evaluate progression-free survival (PFS) in patients with HER2-positive metastatic solid tumors and brain metastases receiving the tucatinib and T-DM1 combination.
  • To evaluate overall survival (OS) in patients with HER2-positive metastatic solid tumors and brain metastases receiving the tucatinib and T-DM1 combination.
  • To evaluate the duration of response to the tucatinib and T-DM1 combination per the RECIST v1.1 in patients with HER2-positive metastatic solid tumors and brain metastases.
  • To evaluate the clinical benefit rate of the tucatinib and T-DM1 combination per the RECIST v1.1 in patients with HER2-positive metastatic solid tumors and brain metastases.

Exploratory Objectives:

  • To assess the effects of the tucatinib and T-DM1 combination on cell proliferation and apoptosis.
  • To evaluate predictive and pharmacodynamic (PD) biomarkers of response and resistance to the tucatinib and T-DM1 combination.
  • To assess the effects of the tucatinib and T-DM1 combination on circulating-free DNA (cfDNA) dynamics.
Being tested
Trastuzumab emtansine, Tucatinib
Medical subject headings
Neoplasm Metastasis, Brain Neoplasms

What participants receive

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

  • Trastuzumab emtansineDrug

    Also called T-DM1, Trastuzumab-MCC-DM1, Kadcyla, ado-trastuzumab emtansine

    Given by IV (vein)

  • TucatinibDrug

    Also called ARRY-380, ONT-380

    Given by PO

Study groups in NCT05673928
Study groupRoleWhat they receive
Tucatinib and Adotrastuzumab Emtansine (T-DM1)ExperimentalEach study cycle is 21 days (3 weeks) Participants will take tablets of tucatinib two (2) times a day, about 8-12 hours apart. Participants will receive T-DM1 by vein over about 30 minutes on Day 1 of each cycle
Receives: Drug: Trastuzumab emtansine; Drug: Tucatinib

What is being measured

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

  1. Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0

    Measured: through study completion; an average of 1 year.

Timeline

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

  1. First posted6 Jan 2023
  2. Study start16 May 2023
  3. Primary completion1 Mar 2027 (estimated)
  4. Study completion1 Mar 2029 (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
30 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05673928
Sponsor's protocol ID
2021-0899
Other IDs
NCI-2022-11157
Status last verified
Jul 2026
First submitted
30 Dec 2022
Last updated
16 Jul 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Trastuzumab emtansine and Tucatinib in people with Metastatic Solid Tumor and Brain Metastases, run by M.D. Anderson Cancer Center at 1 site 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 33 inclusion and 27 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: looking for participants now, as of the sponsor's last update on 16 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 1 site 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?

Contact Ecaterina Dumbrava, MD (713-563-1930, eeileana@mdanderson.org), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0 (time frame: through study completion; an average of 1 year.). 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 NCT05673928.

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 16 Jul 2026.

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