Study of Tucatinib and Doxil in Participants With Human Epidermal Growth Factor Receptor 2 Positive (HER2+) Metastatic Breast Cancer

NCT05748834 | Recruiting Phase 2 FDA Drug

• 1 other identifier: BRE 381
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 8

Brief Summary

This clinical trial is evaluating tucatinib in combination with Doxil in participants with human epidermal growth factor 2 positive (HER2+) locally advanced or metastatic breast cancer. The main goals of this study are to:

• Learn how well the combination of tucatinib and Doxil works
• Learn more about the side effects of the combination of tucatinib and Doxil

Conditions

Breast Cancer

Keywords

Breast Cancer; HER2+; HER2 positive breast cancer; Human epidermal growth factor receptor 2 positive; Doxil; Tucatinib; Tukysa; Anti-HER2; HER2 inhibitor; HER2 blocker; Tyrosine Kinase Inhibitor; Anthracycline

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR) to assess the anti-tumor activity of tucatinib in combination with Doxil using RECIST v1.1.

  Proportion of participants with confirmed complete response (CR) or partial response (PR) to tucatinib in combination with Doxil according to RECIST v1.1 criteria.

  Up to approximately 40 months.

Secondary Outcomes (2)

• Number of participants with treatment-related adverse events as assessed by common terminology criteria for adverse events (CTCAE) v5.0.

  from informed consent (cycle 0 day -28) to 30 days after the last dose of study treatment. Each cycle is 28 days.

• Progression-free survival (PFS) to assess the anti-tumor activity of tucatinib in combination with Doxil using RECIST v1.1.

  Up to approximately 40 months.

Study Arms (1)

Tucatinib Experimental Treatment Arm

EXPERIMENTAL

Participants will receive tucatinib 300mg by mouth twice daily continuously in combination with Doxil 40mg/m2 given intravenously on day 1 of each cycle. Cycles will be 28 days. Up to 36 participants will be enrolled in this Phase 2 study.

Drug: Tucatinib; Drug: Doxil

Interventions

Tucatinib DRUG

Participants will receive tucatinib 300mg by mouth twice daily continuously (days 1-28) of each 28 day cycle.

Also known as: Tukysa

Tucatinib Experimental Treatment Arm

Doxil DRUG

Participants will receive Doxil 40mg/m2 intravenously on day 1 of each 28 day cycle (with a maximum cumulative dose of 550mg/m2).

Also known as: doxorubicin hydrochloride liposome injection

Tucatinib Experimental Treatment Arm

Eligibility Criteria

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

You may qualify if:

• Written informed consent, according to local guidelines, signed and dated by the patient or by a legal guardian prior to the performance of any study-specific procedures, sampling, or analyses
• At least 18 years-of-age at the time of signature of the informed consent form (ICF)
• Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1
• Have a confirmed diagnosis of locally advanced/metastatic HER2+ breast cancer (based on local laboratory testing per American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines immunohistochemistry 3+ (IHC3+) or fluorescence in situ hybridization + (FISH+))
• Have had prior treatment with at least 1 line of anti-HER2 therapy for locally advanced/metastatic disease or relapsed within 6 months of completion of adjuvant anti-HER2 therapy. Prior treatment with tucatinib in the metastatic setting is allowed
• Measurable disease as measured by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
• Females of child-bearing potential should be using adequate contraceptive measures from the time of screening until 6 months following the last dose of study drug(s), should not be breast feeding and must have a negative pregnancy test prior to start of dosing, or must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening:
• Post-menopausal: defined as aged more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments
• Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy, but not tubal ligation
• Women under 50 years-of-age will be considered postmenopausal if they have been amenorrheic for at least 12 months following the cessation of exogenous hormonal treatments, and have serum follicle-stimulating hormone and luteinizing hormone levels in the postmenopausal range for the institution.
• Male patients with female partners of childbearing potential and female patients of childbearing potential are required to use two forms of acceptable contraception, including one barrier method, during their participation in the study and for 6 months following last dose. Male patients must also refrain from donating sperm during their participation in the study.
• Adequate hematologic function
• Absolute neutrophil count (ANC) ≥1500/µL
• Platelet count ≥100,000/µL (no transfusions allowed to meet this requirement)
• Hemoglobin ≥9 g/dL (at least 2-week washout from any transfusion)

You may not qualify if:

• Treatment with any of the following:
• Any systemic anti-cancer chemotherapy or small molecule, biologic, or hormonal agent from a previous treatment regimen or clinical study within 21 days or 5 half-lives (whichever is shorter) prior to the first dose of study drugs. At least 10 days must have elapsed between the last dose of such agent and the first dose of study drugs.
• Prior treatment with anthracycline in any setting
• Major surgery (excluding placement of vascular access) within 28 days of first dose of study drugs
• Palliative radiation therapy within 14 days of first dose of study drugs
• 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 the Medical Monitor and approval for enrollment is granted
• 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 dose of ≤2 mg total daily of dexamethasone (or equivalent) may be eligible with discussion and approval by the Medical Monitor
• Known or suspected leptomeningeal disease (LMD) as documented by the Investigator
• Have poorly controlled (\>1 week) generalized or complex partial seizures, or manifest neurologic progression due to brain metastases, notwithstanding CNS-directed therapy.
• Use of a strong cytochrome P450 (CYP)2C8-inhibitor or use of a strong CYP3A4 or use of a CYP2C8 inducer within 5 days prior to the first dose of study treatment
• With the exception of alopecia, any unresolved toxicities from prior therapy greater than CTCAE Grade 1 at the time of starting study treatment. Note: patients with chronic Grade 2 toxicities who are asymptomatic or adequately managed with stable medication may be eligible with approval by the Medical Monitor.
• Women who are pregnant or nursing or plan to become pregnant while in the study and for at least 6 months after the last administration of study treatment
• Men who plan to father a child while in the study and for at least 6 months after the last administration of study treatment
• Presence of active gastrointestinal disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of tucatinib (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea Grade ≥2, malabsorption syndrome)

Sponsors & Collaborators

• SCRI Development Innovations, LLC: lead
• Seagen Inc.: collaborator
• Pfizer: collaborator

Study Sites (8)

Maryland Oncology Hematology

Columbia, Maryland, 21044, United States

RECRUITING

Alliance Cancer Specialists

Bensalem, Pennsylvania, 19020, United States

RECRUITING

SCRI Oncology Partners

Nashville, Tennessee, 37203, United States

RECRUITING

Tennessee Oncology

Nashville, Tennessee, 37203, United States

ACTIVE NOT RECRUITING

Texas Oncology- DFW

Dallas, Texas, 75246, United States

RECRUITING

Texas Oncology- San Antonio

San Antonio, Texas, 78240, United States

RECRUITING

Virginia Oncology Associates

Norfolk, Virginia, 23502, United States

RECRUITING

Blue Ridge Cancer Care (Oncology & Hematology Assoc of SW Virginia, Inc)

Salem, Virginia, 24153, United States

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

tucatinib; liposomal doxorubicin

Condition Hierarchy (Ancestors)

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

Study Officials

• Erika Hamilton, MD

  SCRI Development Innovations, LLC

  STUDY CHAIR

Central Study Contacts

Sarah Cannon Development Innovations

CONTACT

1-844-710-6157; SCRI.InnovationsMedical@scri.com

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: February 7, 2023
• First Posted: March 1, 2023
• Study Start: July 24, 2023
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): November 1, 2027
• Last Updated: March 20, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (8)