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)

NCT05673928 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 2021-0899NCI-2022-11157
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Brain Metastases; Metastatic Solid Tumor

Outcome Measures

Primary Outcomes (1)

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

  through study completion; an average of 1 year.

Study Arms (1)

Tucatinib and Adotrastuzumab Emtansine (T-DM1)

EXPERIMENTAL

Each 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

Drug: Trastuzumab emtansine; Drug: Tucatinib

Interventions

Tucatinib DRUG

Given by PO

Also known as: ARRY-380, ONT-380

Tucatinib and Adotrastuzumab Emtansine (T-DM1)

Trastuzumab emtansine DRUG

Given by IV (vein)

Also known as: T-DM1, Trastuzumab-MCC-DM1, Kadcyla, ado-trastuzumab emtansine

Tucatinib and Adotrastuzumab Emtansine (T-DM1)

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-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.
• 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

You may not qualify if:

• Patients must not have any of the following on the screening brain MRI:
• Any untreated brain lesions \>3.0 cm in size
• 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.
• 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

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Genentech, Inc.: collaborator
• Seagen Inc.: collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Neoplasm Metastasis; Brain Neoplasms

Interventions

Ado-Trastuzumab Emtansine; tucatinib

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Maytansine; Macrolides; Lactones; Organic Chemicals; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Trastuzumab; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Ecaterina Dumbrava, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ecaterina Dumbrava, MD

CONTACT

713-563-1930; eeileana@mdanderson.org

Study Design

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

Study Record Dates

• First Submitted: December 30, 2022
• First Posted: January 6, 2023
• Study Start: May 16, 2023
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2029
• Last Updated: January 21, 2026

Record last verified: 2026-01

Locations

US (1)