NCT07136428

Asciminib in HER2+ Breast Cancer Brain Metastases

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

• Status: Not Yet Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 42 (estimated)
• Sponsor: Duke University · Academic / Other
• Sex: Female
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

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.

Conditions

• HER2+ Metastatic Breast Cancer

Interventions

Type	Name	Description
COMBINATION_PRODUCT	Asciminib 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.

Timeline

• Start date: 2026-02-01
• Primary completion: 2030-11-01
• Completion: 2032-11-01
• First posted: 2025-08-22
• Last updated: 2025-12-19

Regulatory

• FDA-regulated drug study