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HER2+ Metastatic Breast CancerPhase 1/2ASCENdANTNCT07136428

Asciminib in HER2+ Breast Cancer Brain Metastases

A Phase 1/2 study testing Asciminib and Trastuzumab in people with HER2+ Metastatic Breast Cancer, run by Duke University 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
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
HER2+ Metastatic Breast Cancer
What is being tested?
Asciminib and Trastuzumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
42 participants
Where
1 siteUnited States
Study dates
7 Jul 2026to 1 Nov 2032
Phase
Phase 1/2
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
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • >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
  • Total serum bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) ≤ 2.5 × ULN (or ≤ 5 × ULN if liver metastases are present)
  • Serum creatinine ≤ 1.5 x ULN or estimated creatinine clearance ≥ 50 mL/min as calculated using the Cockcroft-Gault (CG) equation
  • Left ventricular ejection fraction (LVEF) ≥ 50%.
  • Females of childbearing potential must have a negative pregnancy test (serum or urine) at screening. If a pregnancy test using either method is positive or cannot be confirmed as negative, a second testing using the other method will be required for confirmation.
  • Females of childbearing potential and males must be willing to abstain from heterosexual intercourse or to use highly effective contraception
  • Can enroll with intracranial disease only; extracranial disease can be absent or non-measurable
  • Focal leptomeningeal disease allowed at investigator discretion
  • Performance status by Eastern Cooperative Oncology Group (ECOG) 0-2 (appendix 1)
  • Written informed consent and HIPAA authorization for release of personal health information prior to enrollment. NOTE: HIPAA authorization may be included in the informed consent or obtained separately

Who cannot join

  • 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
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  • 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.
  • Central nervous system exclusion - Based on screening brain MRI, patients must not have any of the following:
  • Ongoing use of systemic corticosteroids for control of symptoms of brain metastases at a total daily dose of > 2 mg of dexamethasone (or equivalent)
  • Diffuse leptomeningeal disease or positive CSF cytology; however, discreet dural-based metastases are allowed
  • Poorly controlled seizures. Defined as seizures that continue to occur despite optimal anticonvulsant medications based on investigator discretion.
  • Active infection requiring intravenous systemic therapy.
  • Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
  • Patients with a prior or concurrent malignancy within last 5 years whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen, per treating physician discretion, are not eligible for this trial.
  • Treatment with any investigational drug within 30 days prior to enrollment (Day 1 of study drug).

Trial locations and contacts

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

Carey Anders, MD contact

919-471-8344

carey.anders@duke.edu

Breast Clinic contact

919-660-1278

breastcl@dm.duke.edu

United States1 site, 1 recruiting

  • Duke University

    Durham, North Carolina, 27710

    Carey Anders, MD, 919-471-8344, carey.anders@duke.edu

    Breast Clinic, 919-660-1278, breastcl@dm.duke.edu

    Recruiting

Other trials in United States

About this study

Official title: A Single Arm, Open-label Phase Ib/II Study of Asciminib in HER2+ Breast Cancer Brain Metastases (ASCENdANT)

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.

Read the detailed description

Despite recent advances in the HER2+ space, BrM remain incurable, are associated with significant morbidity, and remain an unmet medical need. Once patients develop resistance to the early-line HER2-directed agents, there are few effective therapies, especially for patients with BrM. ABL kinases are being considered as a potential strategy for treating metastatic cancers, including metastatic HER2+ BC and BrM. The drug asciminib (ABL001, Novartis), an allosteric ABL kinase inhibitor currently FDA approved for treatment of CML. In this single-arm, open label multi-center Phase Ib/II study, patients with stage IV HER2+ BCBrM with at least one progressive or new brain metastasis measuring >5mm will receive asciminib along with standard of care trastuzumab, first as part of a safety lead-in followed by a Phase 2 trial in 13 patients. A 4-15patient safety run-in will be initially conducted to determine the MTD of asciminib/trastuzumab combination therapy, or the maximal safe dose at which patients in the second part of the study will receive. There will be 4 dose levels of combination therapy in the safety run-in. DLTs will be monitored and dose mods will be executed as needed. The treatment period for this study will last for at least 9 cycles. Each cycle will last 21 days. Asciminib will be taken orally at the assigned dose every day during the treatment period. Trastuzumab will be given intravenously (IV) or subcutaneously (SQ) at the assigned dose on Day 1 of each 21 day cycle. Participants will continue on study therapy until disease progression, toxicity, or patient withdrawal.

Being tested
Asciminib and Trastuzumab

What participants receive

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

  • Asciminib and TrastuzumabCombination 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.

Study groups in NCT07136428
Study groupRoleWhat they receive
Asciminib TrastuzumabExperimentalCombination of asciminib and trastuzumab
Receives: Combination Product: Asciminib and Trastuzumab

What is being measured

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

  1. 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

    Measured: Day 1 of treatment until 30 days post last dose

  2. 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).

    Measured: Day 1 of treatment through up to 112 weeks

Secondary outcomes (3)

  1. Median time to progression

    Time to Progression (TTP) (both intracranial or extracranial) as determined by Response Assessment in Neuro-Oncology (RANO) Criteria for Brain Metastases (RANO-BM).

    Measured: Day 1 of treatment through up to 112 weeks

  2. Progression Free Survival (PFS)

    Progression free survival as determined by Response Assessment in Neuro-Oncology (RANO) Criteria for Brain Metastases (RANO-BM).

    Measured: Day 1 of treatment through up to 110 weeks

  3. Overall Survival (OS)

    Patients will be followed till death or off study due to any other reason.

    Measured: Day 1 of treatment through up to 110 weeks

Timeline

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

  1. First posted22 Aug 2025
  2. Study start7 Jul 2026
  3. Primary completion1 Nov 2030 (estimated)
  4. Study completion1 Nov 2032 (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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
42 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07136428
Sponsor's protocol ID
Pro00117131
Acronym
ASCENdANT
Status last verified
Jul 2026
First submitted
15 Aug 2025
Last updated
22 Jul 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Asciminib and Trastuzumab in people with HER2+ Metastatic Breast Cancer, run by Duke University 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 25 inclusion and 22 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 22 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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 Carey Anders, MD (919-471-8344, carey.anders@duke.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of participants with a dose-limiting toxicity at each dose level (time frame: Day 1 of treatment until 30 days post last dose). 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 NCT07136428.

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 22 Jul 2026.

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