Company aims to demonstrate the value of investigational pan-Notch inhibitor in patient population with high unmet need
REHOVOT, Israel & WILMINGTON, Del., Dec 17, 2018 – (BUSINESS WIRE) – Ayala Pharmaceuticals, Inc., a clinical-stage company developing medicines for cancers that are genetically identified, today announced that the first patient has been enrolled in its Phase 2 ACCURACY study, to evaluate lead investigational candidate AL101 in patients with adenoid cystic carcinoma (ACC) bearing Notch activated mutations.
AL101 is a small-molecule that inhibits gamma secretase, an enzyme which plays a key role in the activation of the Notch signaling pathway by releasing the Notch intracellular domain (NICD) which migrates to the nucleus initiating a complex transcription program. In a Phase 1b study (n=94), the recommended Phase 2 dose of 4 mg IV weekly administered every 7 days was established, which was well tolerated in patients with locally advanced or metastatic solid tumors, including ACC.
In prior research, sequencing of ACC tumor samples revealed genomic alterations in the Notch pathway in a subset of patients with a distinct ACC phenotype. ACC patients with Notch1 mutations have an aggressive course of disease with a distinct pattern of metastasis and worse prognosis than their wild type counterparts. In addition to Notch1 mutations, mutations in Notch 2 and 4 were reported in ACC. There is a pressing unmet need as currently there are no available therapies for these patients.
“Based on the promising preclinical and clinical data generated to date, we strongly believe AL101 has potential as a targeted therapy for adenoid cystic carcinoma with notch activated mutations,” said Roni Mamluk, PhD, chief executive officer at Ayala. “The advancement of AL101 into a Phase 2 study is an important milestone in the development of this clinical candidate, as well as for patients suffering from ACC, a rare cancer with high unmet medical need.”
AL101 Phase 2 Trial in Patients with ACC
ACCURACY is a Simon 2-Stage optimal design, non-comparative, open-label, single-arm, multi-center study in patients with ACC bearing activating Notch Mutations. Ayala plans to initially open eight clinical sites in North America, with the potential to expand into Europe and Australia.
AL101 is administered intravenously as a single agent at a dose of 4 mg every 7 days over 28-day cycles until disease progression, unacceptable toxicity or consent withdrawal. The study is designed to evaluate the objective response rate as outlined by Response Evaluation Criteria in Solid Tumors (RECIST v1.1). Secondary endpoints include the frequency, duration and severity of adverse events and serious adverse events, overall survival, progression-free survival and duration of response. In order to meet the criteria for enrollment, patients must have confirmed ACC with known Notch 1/2/3/4 activating mutation that is recurrent or metastatic, not amenable to potentially curative surgery or radiotherapy.
For more information on AL101 ACCURACY study, please visit www.clinicaltrials.gov.