Neoplasms

All Conditions

Rare Diseases

Carcinoma

Carcinoma, Adenoid Cystic

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Adenoid Cystic Carcinoma

Patients receive AL101 IV over 60 minutes QW for 6-8 weeks in the absence of disease progression or unacceptable toxicity. Within 24-72 hours after the last infusion of AL101, patients undergo surgery per standard of care. Patients may continue AL101 after surgery at the discretion of the study doctor.

AL101

Therapeutic Conventional Surgery

Renata Ferrarotto

This phase Ib trial studies the side effects and possible benefits of AL101 before surgery in treating patients with notch activated adenoid cystic cancer. AL101 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving AL101 before surgery may help to control adenoid cystic cancer that has a NOTCH pathway activation.

PRIMARY OBJECTIVES:

I. To evaluate the safety and feasibility of AL101 administered weekly for 6 to 8 weeks in the preoperative setting using National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

II. To determine the differences between NICD1 levels by immunohistochemistry (IHC) in the post-treatment surgical specimens as compared to baseline in patients treated with AL101.

SECONDARY OBJECTIVES:

I. To evaluate the objective response rate (ORR) to AL101 by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 at 6 to 8 weeks.

II. To assess percentage of patients undergoing the initially proposed surgery. III. To assess percentage of viable tumor cells in the surgical specimen (pathologic response) following AL101 treatment.

EXPLORATORY OBJECTIVE:

I. To evaluate pre- and post- treatment tumor and blood biomarkers and correlate with clinical and pathologic response and toxicity.

OUTLINE:

Patients receive AL101 intravenously (IV) over 60 minutes once weekly (QW) for 6-8 weeks in the absence of disease progression or unacceptable toxicity. Within 24-72 hours after the last infusion of AL101, patients undergo surgery per standard of care. Patients may continue AL101 after surgery at the discretion of the study doctor.

After completion of study, patients are followed up within 6 weeks after surgery or within 30 days after last dose of AL101, and then every 6 months thereafter.

AL101 Before Surgery for the Treatment of Notch Activated Adenoid Cystic Cancer

AL101 Prior to Standard-of-Care Surgery in Patients With Notch Activated Adenoid Cystic Carcinoma (ACC)

Adverse events will be graded by National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Frequency tables will summarize toxicity data for all patients. Logistic regression may be utilized to assess the effect of patient prognostic factors on the response and toxicity.

Evaluated by immunohistochemistry in the post-treatment surgical specimen (at 6 to 8 weeks) as compared to baseline (pre-treatment) in patients treated with AL101

Evaluated per Response Evaluation Criteria in Solid Tumors. Logistic regression may be utilized to assess the effect of patient prognostic factors on the response and toxicity.

M.D. Anderson Cancer Center

AL101 is an inhibitor of gamma secretase-mediated Notch signaling.

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

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

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

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

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.

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 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.

Ayala Pharmaceuticals, Inc,

The analysis was done on the safety population which consists of 87 patients (45 patients in the 4mg arm, and 42 patients in the 6mg arm) Safety analysis set includes all subjects who receive at least one infusion of study drug, including partial infusions..

AL101 4 mg once weekly (QW) intravenously (IV)

Cohort 1 - AL101 4mg

AL101 6 mg mg once weekly (QW) intravenously (IV)

Cohort 2 - AL101 6mg

AL101 6 mg once weekly (QW) intravenously (IV)

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

Canada

Netherlands

United States

United Kingdom

Israel

France

Spain

Region of Enrollment

Chief Medical Officer

Efficacy evaluable analysis set includes all subjects who receive at least one complete infusion of study drug, have measurable disease at baseline per RECIST v1.1 or modified MDA criteria for bone-exclusive disease and have at least one post-baseline on-study assessment of tumor response.

Overall Response Rate (ORR)

Clinical Benefit Response Rate (CBR)

Overall Survival

Overall Study

Skin and Connective Tissue Diseases

Breast Neoplasms

Triple Negative Breast Neoplasms

Breast Diseases

Skin Diseases

The study included a lead-in cohort with 6 subjects at 6mg AL101 weekly. 13 additional patients were treated with 4mg AL101 weekly.

Andres Gutierrez, MD, PhD

The current study is designed to evaluate the efficacy and safety of AL101 monotherapy in subjects with Notch-activated recurrent or metastatic TNBC; Notch activation will be determined by a Next Generation Sequencing (NGS) test.

A Study of AL101 Monotherapy in Patients With Notch Activated Triple Negative Breast Cancer

A Phase 2, Multi-center, Open-label, Single Arm Study of AL101 Monotherapy in Patients With Notch Activated Triple Negative Breast Cancer

Duration of response (DOR) is defined as the time from randomization to disease progression or death in patients who achieve complete or partial response.

The analysis was done on the safety population which consists of 18 patients (6 patients in the 6mg arm, and 12 patients in the 4mg arm)

AL101 is an inhibitor of gamma secretase-mediated Notch signaling.

.

AL101 6mg

AL101 4mg

AL101 is an inhibitor of gamma secretase-mediated Notch signaling. 4mg of AL101 was administered using an IV infusion pump over 60 minutes, once a week.

AL101 is an inhibitor of gamma secretase-mediated Notch signaling. 6mg of AL101 was administered using an IV infusion pump over 60 minutes, once a week.

19 patients were enrolled, only 18 were treated.

Belgium

Duration of response data was not collected as there were no patients with either CR or PR

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
AL101 Before Surgery for the Treatment of Notch Activated Adenoid Cystic Cancer	NCT04973683	Adenoid Cystic ... Metastatic Aden...	AL101 Therapeutic Con...	18 Years -	M.D. Anderson Cancer Center
A Study Of AL101In Patients With Adenoid Cystic Carcinoma (ACC) Bearing Activating Notch Mutations	NCT03691207	Adenoid Cystic ...	AL101	18 Years -	Ayala Pharmaceuticals, Inc,
A Study of AL101 Monotherapy in Patients With Notch Activated Triple Negative Breast Cancer	NCT04461600	Triple Negative...	AL101	18 Years -	Ayala Pharmaceuticals, Inc,

Spots Global Cancer Trial Database for al101

Every month we try and update this database with for al101 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for al101

Every month we try and update this database with for al101 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for al101 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.