Most common sites of metastases, n (%) b Lung Bone Liver Race, n (%) White Black Asian Other/not reportedĭisease status at screening, n (%) b Metastatic Local recurrence Treatment naïve and metastatic Table: 904Pĭisposition and baseline characteristics of subjects treated with AL101 a ResultsĪ total of 37 subjects were enrolled in the 6-mg QW cohort. The study provides ≥80% power to detect an increase of the ORR from 8% to 25% using a type I error of 5%. Secondary end points were ORR by central review, duration of response, and safety. Primary end point was overall response rate (ORR) by RECIST v1.1 (or modified MD Anderson bone criteria), as assessed by investigators. Subjects require evidence of disease progression within 6 months of entry or newly diagnosed metastatic disease and an ECOG performance status of 0-1. MethodsĪCCURACY is an open-label, multicenter phase II study of AL101 (4 and 6 mg intravenous QW) in subjects with R/M ACC and known Notch1-4 mut (ASCO ‘19, Abstr TPS6098). Based on the safety and activity in the 4-mg cohort, a cohort of 42 additional subjects was added to evaluate treatment with 6 mg QW. 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). AL101, an investigational γ-secretase inhibitor, blocks Notch signaling and inhibits tumors in ACC patient-derived xenograft models with Notch mut (AACR ‘19, Abstr 4885). Notch mut are found in ∼20% of ACC tumors, which are aggressive with a poor prognosis (Ferrarotto 2016, Ho 2019). Notch signaling plays a key role in ACC tumorigenesis.

19 Thoracic Head And Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, 77030 - Houston/US.

18 Ayala Pharmaceuticals, Inc., Ayala Pharmaceuticals, Inc., 19801 - Wilmington/US.

17 Department Of Medical Oncology, Keck Hospital of USC, USC Norris Comprehensive Cancer Center, 90033 - Los Angeles/US.

16 Endocrine Oncology Clinic, Michigan Medicine University of Michigan, 48109 - Ann Arbor/US.

15 Hematology/oncology, Massachusetts General Hospital, 02114 - Boston/US.

14 Department Of Oncology, University of Western Ontario, N6A 3K7 - London/CA.

13 Department Of Medical Oncology, Radboud University Medical Center, 6525 - Nijmegen/NL.

12 Institute Of Oncology, Rabin Medical Center, 4941492 - Petah Tikva/IL.11 Clinical Research Division, University of Washington/Fred Hutchinson Cancer Research Center, 98195 - Seattle/US.10 Sharett Institute Of Oncology, Hadassah Medical Center, 9103401 - Jerusalem/IL.9 Division Of Medical Oncology, Sylvester Comprehensive Cancer Center, 33136 - Miami/US.8 Phase 1/drug Development Program, Catalan Institute of Oncology (ICO) L’Hospitalet, 08908 - Barcelona/ES.Lee Moffitt Cancer Center & Research Institute, 33612 - Tampa/US 7 Head And Neck And Endocrine Oncology, H.

6 Department Of Head And Neck, The Christie NHS Foundation Trust, M20 4BX - Manchester/GB.5 Hematology/oncology, University of California San Francisco, Helen Diller Family Comprehensive Cancer Center, CA, 94143 - San Francisco/US.4 Medical Oncology Department, Tom Baker Cancer Centre, T2N 4N2 - Calgary/CA.3 Head And Neck Department, Institut Gustave Roussy, 94800 - Villejuif/FR.2 Division Of Medical Oncology, University of Colorado Cancer Center, 80045 - Aurora/US.

Lauder Breast Center, 10065 - New York/US 1 Medicine, Memorial Sloan Kettering Evelyn H.

Research site gamma control