A Single Arm, Open-label Phase Ib/II Study of Asciminib in HER2+ Breast Cancer Brain Metastases (ASCENdANT)
Duke University
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.
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, pati…
Eligibility
- Age range
- 18+ years
- Sex
- Female
- Healthy volunteers
- No
Inclusion Criteria: * 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 pe…
Interventions
- Combination ProductAsciminib and Trastuzumab
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.
Location
- Duke UniversityDurham, North Carolina