Phase 1b/2 asciminib allosteric BCR-ABL inhibitor + trastuzumab HER2 mAb in HER2+ BrM

Duke University is running ASCENdANT, a single-arm, open-label Phase 1b/2 study testing asciminib plus trastuzumab for patients with metastatic HER2-positive breast cancer with brain metastases, with the primary goal of measuring intracranial response. Asciminib (Scemblix; Novartis) is an allosteric ABL kinase inhibitor approved in CML and repurposed here based on evidence implicating ABL signaling in HER2-driven metastatic disease; eligible patients generally must already have received both T-DXd and tucatinib. The key scientific angle is whether adding a repurposed ABL inhibitor to continued HER2 antibody therapy can improve brain lesion control without switching immediately to other HER2-directed ADCs or TKIs. For many patients with HER2+ metastatic disease and brain metastases, today’s care commonly combines local therapy (stereotactic radiosurgery and/or surgery when feasible) with systemic HER2 regimens such as trastuzumab deruxtecan (AstraZeneca/Daiichi Sankyo) and/or tucatinib + trastuzumab + capecitabine (Seagen/Pfizer plus Genentech/Roche), with treatment choice shaped by prior lines and CNS activity.