Asciminib in HER2+ Breast Cancer Brain Metastases

NCT07136428 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: Pro00117131
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the intracranial response rate of a combination of asciminib/trastuzumab for the treatment of patients with metastatic HER2+ breast cancer with brain metastases.

Conditions

HER2+ Metastatic Breast Cancer

Outcome Measures

Primary Outcomes (2)

• Number of participants with a dose-limiting toxicity at each dose level

  Safety of administering asciminib in combination with trastuzumab by measuring number of participants with a dose-limiting toxicity at each dose level

  Day 1 of treatment until 30 days post last dose

• Number of participants with a complete response (CR) or partial response (PR)

  Efficacy at maximum tolerated dose (MTD) determined by the number of participants with a complete response (CR) or partial response (PR) as determined by Response Assessment in Neuro-Oncology (RANO) Criteria for Brain Metastases (RANO-BM).

  Day 1 of treatment through up to 112 weeks

Secondary Outcomes (3)

• Median time to progression

  Day 1 of treatment through up to 112 weeks

• Progression Free Survival (PFS)

  Day 1 of treatment through up to 110 weeks

• Overall Survival (OS)

  Day 1 of treatment through up to 110 weeks

Study Arms (1)

Asciminib Trastuzumab

EXPERIMENTAL

Combination of asciminib and trastuzumab

Combination Product: Asciminib and Trastuzumab

Interventions

Asciminib and Trastuzumab COMBINATION_PRODUCT

Each study treatment cycle will last 21 days. Asciminib will be taken orally every day during the treatment period at the dose determined as the MTD during the safety lead-in in combination with trastuzumab at a standard dose of 6mg/kg IV. Asciminib dose will begin at 80 mg daily (dose level 1), with a potential range from 40 mg daily (dose level -1A, with trastuzumab) to 200 mg bid (dose level 3, with trastuzumab) depending on the results of the safety lead-in. Trastuzumab will be given intravenously (IV) or subcutaneously (SQ) on Day 1 of each 21 day cycle.

Asciminib Trastuzumab

Eligibility Criteria

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

You may qualify if:

• Age ≥18 years at the time of consent
• Patients with HER2+ metastatic breast cancer with at least one progressive or new brain metastasis measuring \>5mm; prior local therapy to other intracranial lesions allowed
• At least 1 prior standard of care therapy for metastatic disease
• Must have previously received T-DXd and Tucatinib. If a patient has not received T-DXd or Tucatinib as part of standard early line therapy due to allergies or intolerability, the requirement of prior T-DXd and Tucatinib treatment is waived.
• Participants must have adequate treatment washout period when applicable before enrollment, defined as:
• \>4 weeks from any major surgery
• \>1 week from any cranial radiation treatment
• For cytotoxic containing agents, 5 half-lives or at least 21 days (whichever is shorter)
• For weekly chemotherapy regimens, \>2 weeks from chemotherapy; for every 3 weekly regimens, \>3 weeks from chemotherapy. At least 2 weeks from other systemic or targeted or investigational therapies (other than endocrine therapy) for breast cancer. No washout is required for endocrine therapy (e.g. aromatase inhibitors, tamoxifen, fulvestrant) but patients should discontinue prior to start of protocol therapy.
• Patients on ovarian suppression are allowed (but not required) to continue ovarian suppression at the discretion of their treating provider.
• Adequate organ function and bone marrow reserve as determined by the investigator
• Adequate hepatic and renal function and hematologic parameters:
• Absolute neutrophil count (ANC) ≥ 1.0 × 109/L
• Platelets ≥ 100 × 109/L
• Hemoglobin ≥ 9 g/dL

You may not qualify if:

• No evidence of hemorrhage or impending herniation or need for immediate local therapy to intracranial disease or escalating dosing of steroids
• No grade 2 or greater peripheral neuropathy
• Diffuse and symptomatic leptomeningeal carcinomatosis
• Prolonged Qtc (QTcF\>450), CHF or uncontrolled HTN
• Clinically significant cardiopulmonary disease.
• Acute or chronic pancreatitis within 6 months prior to first day of study treatment
• Clinically significant acute infection requiring systemic antibacterial, antifungal, or antiviral therapy including:
• tuberculosis (clinical evaluation that includes clinical history, physical examination, and radiographic findings, and TB testing in line with local practice),
• hepatitis B (known positive HBV surface antigen (HBsAg) result) ,
• hepatitis C (note: hepatitis C testing at screening will only be performed on those at high risk or with known history), or
• human immunodeficiency virus (positive HIV 1/2 antibodies) (note: HIV testing at screening will only be performed on those at high risk or with known history)
• NOTE: Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody \[anti-HBc\] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA. Subjects with HIV/AIDS with adequate antiviral therapy to control viral load would be allowed if they are stable and have been on treatment for ≥ 4 weeks prior to first dose of study drug(s). Subjects with viral hepatitis with controlled viral load would be allowed while on suppressive antiviral therapy. Testing not required.
• Unable for any reason to undergo MRI of the brain.
• Use of a strong cytochrome P450 (CYP)3A4 inhibitor within 5 half-lives of study treatment. .. Unable to avoid certain CYP3A4 or CYP2C9 substrates which cannot be co-administered with study treatment given altered substrate concentrations.
• Ongoing use of systemic corticosteroids for control of symptoms of brain metastases at a total daily dose of \> 2 mg of dexamethasone (or equivalent)

Sponsors & Collaborators

• Duke University: lead
• Novartis: collaborator

Study Sites (1)

Duke University

Durham, North Carolina, 27710, United States

RECRUITING

MeSH Terms

Interventions

asciminib; Trastuzumab

Intervention Hierarchy (Ancestors)

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

Central Study Contacts

Carey Anders, MD

CONTACT

919-471-8344; carey.anders@duke.edu

Breast Clinic

CONTACT

919-660-1278; breastcl@dm.duke.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 15, 2025
• First Posted: August 22, 2025
• Study Start: July 7, 2026
• Primary Completion (Estimated): November 1, 2030
• Study Completion (Estimated): November 1, 2032
• Last Updated: July 22, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)