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

Ayala Pharmaceuticals, Inc,87 enrolled

Overview

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.

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

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Adenoid Cystic Carcinoma

Interventions

AL101DRUG

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

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (17)

USC Norris Comprehensive Cancer center

Los Angeles, California, United States

University of Colorado Cancer Center

Aurora, Colorado, United States

Outcomes

Primary Outcomes

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.

Time frame: 3 years and 7 months

Secondary Outcomes

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.

Time frame: 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.

Time frame: 3 years and 5 months

Data from ClinicalTrials.gov

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