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

A Phase 2, Open-Label, Multi-center Study of AL101 in Patients With Adenoid Cystic Carcinoma (ACC) Bearing Activating Notch Mutations

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.

Study Overview

• Status: Completed
• Conditions: Adenoid Cystic Carcinoma
• Intervention / Treatment: Drug: AL101

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

• Study Type: Interventional
• Enrollment (Actual): 87
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Tom Baker Cancer Centre
  • Ontario
    • Hamilton, Ontario, Canada, L8V 1C3
      • Hamilton Health Sciences Juravinski Cancer Centre
    • London, Ontario, Canada, N6A 5W9
      • London Health Sciences Center
• France
  • Villejuif, France, 94800
    • Institut Gustave Roussy
• Israel
  • Petah Tikva, Israel, 49100
    • Rabin Medical Center
• Netherlands
  • Nijmegen, Netherlands, 6500
    • Radboud University
• United Kingdom
  • Manchester, United Kingdom, M20 4BX
    • The Christie NHS Foundation Trust
• United States
  • California
    • Los Angeles, California, United States, 90033
      • USC Norris Comprehensive Cancer Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Cancer Center
  • Florida
    • Miami, Florida, United States, 33136
      • Sylvester Comprehensive Cancer Center
    • Tampa, Florida, United States, 33612
      • H. Lee Moffitt Cancer Center & Research Institute
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland School of Medicine
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Minnesota
    • Rochester, Minnesota, United States, 55902
      • Mayo Clinic Hospital
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 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.
2. Evidence of radiographic or clinical disease progression within 6-months of signing informed consent; newly diagnosed metastatic patients will be allowed.
3. Patients must have Formalin-fixed, Paraffin-embedded tissue available .
4. Must have at least 1 target lesion that is measurable for patients with nodal or visceral metastasis.

Exclusion Criteria:

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: SINGLE-ARM; AL101 is an inhibitor of gamma secretase-mediated Notch signaling.

Drug: AL101; 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) of all four Notch receptors from the membrane. In patients with aberrant Notch signaling, AL101 may inhibit Notch signaling and potentially impede tumor growth.The drug is administered intravenously; Other Names: BMS 906024

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR)	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.	3 years and 7 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Benefit Response Rate (CBR)	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.	3 years and 7 months
Overall Survival	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.	3 years and 5 months

Collaborators and Investigators

• Sponsor: Ayala Pharmaceuticals, Inc,

Study record dates

Study Major Dates

• Study Start (Actual): December 14, 2018
• Primary Completion (Actual): July 15, 2022
• Study Completion (Actual): December 2, 2022

Study Registration Dates

• First Submitted: September 22, 2018
• First Submitted That Met QC Criteria: September 25, 2018
• First Posted (Actual): October 1, 2018

Study Record Updates

• Last Update Posted (Estimated): January 31, 2024
• Last Update Submitted That Met QC Criteria: January 8, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Carcinoma; Carcinoma, Adenoid Cystic
• Other Study ID Numbers: AL-ACC-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No