On June 6, 2022 Ayala Pharmaceuticals, Inc. (Nasdaq: AYLA), a clinical-stage oncology company focused on developing and commercializing small molecule therapeutics for patients suffering from rare and aggressive cancers, primarily in genetically defined patient populations, reported that data on AL101 from the Phase 2 ACCURACY study in a poster at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting taking place June 3-7, 2022 in Chicago, Illinois (Press release, Ayala Pharmaceuticals, JUN 6, 2022, View Source [SID1234615633]).
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The poster at ASCO (Free ASCO Whitepaper) provides updated data from the 4mg and 6 mg AL101 cohorts in the ACCURACY study of the AL101, a selective gamma-secretase inhibitor, in subjects with recurrent/metastatic (R/M) adenoid cystic carcinoma (ACC) harboring Notch activating mutations (Notchmut) (NCT03691207). The most recent safety efficacy, PK, and PD data from the study is presented. The abstract from this study has been released on the 2022 ASCO (Free ASCO Whitepaper) Annual Meeting website (View Source).
"We are excited to have AL101 featured in the 2022 ASCO (Free ASCO Whitepaper) meeting and are pleased with the very promising safety and efficacy data from ACCURACY," said Gary Gordon, M.D., Ph.D., Chief Medical Officer of Ayala. "ACC is an orphan disease with no approved therapies and patients with Notch mutations have a more aggressive disease course and poorer survival outcomes as compared to patients with Notch wild-type. If approved, we see strong potential for AL101 to provide a much needed treatment option for R/M ACC patients and look forward to further advancing this clinical program."
ACCURACY is an open-label, single-arm, multicenter Phase 2 study to assess the clinical activity of AL101 using radiographic assessments of patients with R/M ACC demonstrating disease progression within 6 months prior to dosing. It is the first ACC study selecting subjects with ACC bearing defined NOTCH-activating mutations. A total of 87 patients were enrolled (all with RECIST v1.1 evaluable disease or bone exclusive disease deemed evaluable by MD Anderson Bone Response criteria) and of these, 77 were evaluable for efficacy. Approximately 90% of the patients had metastatic disease at screening. This was a heavily pretreated patient population with over half having previously received some form of systemic therapy. Preliminary data from the study were announced by Ayala in 2021.
Efficacy Results
In the 4mg dose group, 6 patients (14.6%) had a partial response, 23 (56.1%) had stable disease, for an overall disease control rate of 70.7%
In the 6mg dose group, 3 patients (8.3%) had a partial response, 21 (58.3%) had stable disease and for an overall disease control rate of 66.7%
Fifty six percent of the 4mg cohort patients and 36% of the 6mg cohort patients experienced some degree of tumor regression.
The median progression free survival (PFS) in each of the 4mg and 6mg dose cohorts was 3.7 months but was 6.7 months among the patients who had a partial response
Median overall survival (OS) was 9.3 months in the overall group but 12.1 months among the patients who had a partial response.
Both dose regimens demonstrated substantial inhibition of the NOTCH pathway consistent with previous studies, but the higher dose did not improve the observed outcomes
Safety
AL101 was adequately tolerated with most adverse events being Grade 1 or 2
Among all 87 patients, 54 or 62% had treatment related grade 3 or 4 AEs (49% in the 4mg cohort and 76% in the 6mg cohort).
Dr. Renata Ferrarotto, Associate Professor and Director of Head and Neck Oncology Clinical Research at M.D. Anderson Cancer Center and the principal investigator of the study commented "The anti-tumor activity of AL101 in the ACCURACY study suggests that it is providing benefit to a subset of patients with ACC carrying Notch-activating mutations. We are presenting data for the first time showing that subjects who had a partial response to AL101 had progression free survival that was approximately double that of the group as a whole. This result, together with the high disease control rate observed, underscores the clinical relevance of the outcomes, given the aggressive disease course associated with Notch mutations and the fact that the majority of subjects in this trial were heavily pretreated."
Poster presentation details:
Abstract Title: Results of ACCURACY: A phase 2 trial of AL101, a selective gamma secretase inhibitor, in subjects with recurrent/metastatic (R/M) adenoid cystic carcinoma (ACC) harboring Notch activating mutations (Notchmut)
Abstract Number: 6046
Session Title: Head and Neck Cancer
Session Date and Time: Monday, June 6, 2022, 1:15 PM-4:15 PM CDT
A copy of the poster will be available on the Ayala corporate website, following the presentation at ASCO (Free ASCO Whitepaper) on June 6.
About Adenoid Cystic Carcinoma (ACC)
ACC is a rare malignancy of the secretory glands including salivary glands, accounting for about 10% of all salivary gland tumors with an annual incidence of 3,400 in the U.S. There is currently no approved standard of care for patients with recurrent/metastatic ACC. Patients with locoregional disease undergo surgery and radiation therapy, with recurring disease treated by chemotherapy. ACC is an immunologically "cold" tumor that is refractory to chemotherapy, with a recurrence rate of about 60% after initial surgery. The Notch pathway has been determined to be an oncogenic driver of ACC and its dysregulation plays a key role in tumorigenesis and correlates with a distinct pattern of metastasis and a poor prognosis.
About AL101
AL101 is an investigational small molecule Gamma Secretase Inhibitor (GSI) that is designed to potently and selectively inhibit Notch 1, 2, 3 and 4, and is currently being evaluated in the Phase 2 ACCURACY clinical studies in patients with adenoid cystic carcinoma (ACC). AL101 is designed to inhibit the expression of Notch gene targets by blocking the final cleavage step by the gamma secretase required for Notch activation. Ayala obtained an exclusive, worldwide license to develop and commercialize AL101 from Bristol-Myers Squibb Company in November 2017. AL101 was granted U.S. FDA Fast Track Designation and Orphan Drug Designation for the treatment of ACC.