A Study Of AL101In Patients With Adenoid Cystic Carcinoma (ACC) Bearing Activating Notch Mutations

Phase 2

Completed

Brief Summary: This is a Phase 2, non comparative, open label, multicenter study of AL101 in patients with recurrent or metastatic ACC who harbor NOTCH 1,2,3,4 activating mutations.

Detailed Description: This is a Phase 2, non-comparative, open-label, multicenter study of AL101 in patients with recurrent or metastatic ACC who harbor NOTCH 1,2,3,4 activating mutations.

The study includes 2 cohorts, ran in a sequential fashion:

Cohort 1 - AL101 4 mg once weekly (QW) intravenously (IV) Cohort 2 - AL101 6 mg QW IV

Recruitment & Eligibility

Inclusion Criteria

Confirmed Adenoid Cystic Carcinoma with known NOTCH 1/2/3/4 activating mutation that is recurrent or metastatic, not amenable to potentially curative surgery or radiotherapy.
Evidence of radiographic or clinical disease progression within 6-months of signing informed consent; newly diagnosed metastatic patients will be allowed.
Patients must have Formalin-fixed, Paraffin-embedded tissue available .
Must have at least 1 target lesion that is measurable for patients with nodal or visceral metastasis.

Exclusion Criteria

Diagnosed with a malignancy other than ACC in the past 2 years.
Uncontrolled, Active Infection
Gastrointestinal (GI) disease with increased risk of diarrhea [e.g. inflammatory bowel disease (IBD)]
Symptomatic central nervous system (CNS) metastases.
Unstable or severe uncontrolled medical condition
Eastern Cooperative Oncology Group (ECOG) performance status ≥2.
Abnormal organ and marrow function

Arm && Interventions

Group	Intervention	Description
SINGLE-ARM	AL101	AL101 is an inhibitor of gamma secretase-mediated Notch signaling.

Primary Outcome Measures

Name	Time	Method
Overall Response Rate (ORR)	3 years and 7 months	ORR is defined as partial response (PR) + complete response (CR) as assessed by the investigator based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 for target lesions assessed by MRI. Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Secondary Outcome Measures

Name	Time	Method
Clinical Benefit Response Rate (CBR)	3 years and 7 months	Clinical benefit response rate (CBR) is defined as complete response (CR) + partial response (PR) + stable disease (SD) by investigator review based on RECIST v1.1 for target lesions assessed by MRI. Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease (SD): Neither sufficient shrinkage (at least 30%) to qualify for PR nor sufficient increase (more than 20%) to qualify for PD, taking as reference the smallest sum diameters.
Overall Survival	3 years and 5 months	Overall survival is defined at the time from first infusion of investigational product to death due to any cause. Subjects with no documentation of death were censored at the last known date known to be alive.

Locations (17): Radboud University
🇳🇱
Nijmegen, Netherlands
Tom Baker Cancer Centre
🇨🇦
Calgary, Alberta, Canada
Memorial Sloan Kettering Cancer Center
🇺🇸
New York, New York, United States
Hamilton Health Sciences Juravinski Cancer Centre
🇨🇦
Hamilton, Ontario, Canada
USC Norris Comprehensive Cancer center
🇺🇸
Los Angeles, California, United States
H. Lee Moffitt Cancer Center & Research Institute
🇺🇸
Tampa, Florida, United States
University of Colorado Cancer Center
🇺🇸
Aurora, Colorado, United States
Sylvester Comprehensive Cancer Center
🇺🇸
Miami, Florida, United States
Massachusetts General Hospital
🇺🇸
Boston, Massachusetts, United States
Mayo Clinic Hospital
🇺🇸
Rochester, Minnesota, United States
MD Anderson Cancer Center
🇺🇸
Houston, Texas, United States
Fred Hutchinson Cancer Research Center
🇺🇸
Seattle, Washington, United States
University of Maryland School of Medicine
🇺🇸
Baltimore, Maryland, United States
Rabin Medical center
🇮🇱
Petah Tikva, Israel
London Health Sciences Center
🇨🇦
London, Ontario, Canada
Institut Gustave Roussy
🇫🇷
Villejuif, France
The Christie NHS Foundation Trust
🇬🇧
Manchester, United Kingdom