904P ACCURACY: A phase II trial of AL101, a selective gamma secretase inhibitor, in subjects with recurrent/metastatic (R/M) adenoid cystic carcinoma (ACC) harboring Notch activating mutations (Notchmut): Results of 6-mg cohort

Abstract

Notch signaling plays a key role in ACC tumorigenesis. Notchmut are found in ∼20% of ACC tumors, which are aggressive with a poor prognosis (Ferrarotto 2016, Ho 2019). No therapies are approved for R/M ACC. AL101, an investigational γ-secretase inhibitor, blocks Notch signaling and inhibits tumors in ACC patient-derived xenograft models with Notchmut (AACR ‘19, Abstr 4885). AL101 has clinical activity at 4 mg once weekly (QW) with a disease control rate of 68% (15% partial response) and appears to be well tolerated (Ferrarotto ESMO ‘20, #919MO).