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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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| SINGLE-ARM | Experimental | AL101 is an inhibitor of gamma secretase-mediated Notch signaling. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| AL101 | Drug | 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 |
| 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 |
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| USC Norris Comprehensive Cancer center | Los Angeles | California | 90033 | United States | ||
| University of Colorado Cancer Center |
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| ID | Title | Description |
|---|---|---|
| FG000 | Cohort 1 - AL101 4mg | AL101 4 mg once weekly (QW) intravenously (IV) |
| FG001 | Cohort 2 - AL101 6mg | AL101 6 mg once weekly (QW) intravenously (IV) |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Sep 23, 2020 | Dec 4, 2023 |
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Open label
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|
|
| 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 |
| Aurora |
| Colorado |
| 80045 |
| United States |
| Sylvester Comprehensive Cancer Center | Miami | Florida | 33136 | United States |
| H. Lee Moffitt Cancer Center & Research Institute | Tampa | Florida | 33612 | United States |
| University of Maryland School of Medicine | Baltimore | Maryland | 21201 | United States |
| Massachusetts General Hospital | Boston | Massachusetts | 02114 | United States |
| Mayo Clinic Hospital | Rochester | Minnesota | 55902 | United States |
| Memorial Sloan Kettering Cancer Center | New York | New York | 10065 | United States |
| MD Anderson Cancer Center | Houston | Texas | 77030 | United States |
| Fred Hutchinson Cancer Research Center | Seattle | Washington | 98109 | United States |
| Tom Baker Cancer Centre | Calgary | Alberta | T2N 4N2 | Canada |
| Hamilton Health Sciences Juravinski Cancer Centre | Hamilton | Ontario | L8V 1C3 | Canada |
| London Health Sciences Center | London | Ontario | N6A 5W9 | Canada |
| Institut Gustave Roussy | Villejuif | 94800 | France |
| Rabin Medical center | Petah Tikva | 49100 | Israel |
| Radboud University | Nijmegen | 6500 | Netherlands |
| The Christie NHS Foundation Trust | Manchester | M20 4BX | United Kingdom |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Cohort 1 - AL101 4mg | AL101 4 mg once weekly (QW) intravenously (IV) |
| BG001 | Cohort 2 - AL101 6mg | AL101 6 mg once weekly (QW) intravenously (IV) |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| ||||||||||||||||||
| Age, Continuous | Median | Full Range | Years |
| |||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||||
| Region of Enrollment | Number | participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | 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. | Posted | Count of Participants | Participants | 3 years and 7 months |
|
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| |||||||||||||||||||||||||||||
| Secondary | 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. | 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. | Posted | Count of Participants | Participants | 3 years and 7 months |
|
| ||||||||||||||||||||||||||||||
| Secondary | 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. | 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. | Posted | Median | 95% Confidence Interval | months | 3 years and 5 months |
|
|
3 years and 7 months
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..
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Cohort 1 - AL101 4mg | AL101 4 mg once weekly (QW) intravenously (IV) | 41 | 45 | 23 | 45 | 45 | 45 |
| EG001 | Cohort 2 - AL101 6mg | AL101 6 mg mg once weekly (QW) intravenously (IV) | 26 | 42 | 26 | 42 | 42 | 42 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pneumonia | Infections and infestations | Systematic Assessment |
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| Sepsis | Infections and infestations | Systematic Assessment |
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| Clostridium difficile colitis | Infections and infestations | Systematic Assessment |
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| Abdominal abscess | Infections and infestations | Systematic Assessment |
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| Abdominal infection | Infections and infestations | Systematic Assessment |
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| Anorectal infection | Infections and infestations | Systematic Assessment |
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| Appendicitis | Infections and infestations | Systematic Assessment |
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| Brain abscess | Infections and infestations | Systematic Assessment |
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| Campylobacter sepsis | Infections and infestations | Systematic Assessment |
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| Cellulitis | Infections and infestations | Systematic Assessment |
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| Cellulitis orbital | Infections and infestations | Systematic Assessment |
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| Meningitis bacterial | Infections and infestations | Systematic Assessment |
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| Pneumonia pseudomonal | Infections and infestations | Systematic Assessment |
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| Skin infection | Infections and infestations | Systematic Assessment |
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| Staphylococcal infection | Infections and infestations | Systematic Assessment |
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| Streptococcal bacteraemia | Infections and infestations | Systematic Assessment |
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| Pneumonia aspiration | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Dyspnoea | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Respiratory failure | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Acute respiratory distress syndrome | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Bronchial obstruction | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Eosinophilic pneumonia | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Haemoptysis | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Hypoxia | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Pleural effusion | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Pneumonitis | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | Systematic Assessment |
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| Dysphagia | Gastrointestinal disorders | Systematic Assessment |
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| Ileus | Gastrointestinal disorders | Systematic Assessment |
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| Inguinal hernia | Gastrointestinal disorders | Systematic Assessment |
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| Brain cancer metastatic | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
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| Brain neoplasm | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
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| Keratoacanthoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
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| Metastases to central nervous system | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
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| Squamous cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
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| Haemorrhage intracranial | Nervous system disorders | Systematic Assessment |
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| Cerebrovascular accident | Nervous system disorders | Systematic Assessment |
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| Encephalopathy | Nervous system disorders | Systematic Assessment |
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| Transient ischaemic attack | Nervous system disorders | Systematic Assessment |
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| Infusion related reaction | Injury, poisoning and procedural complications | Systematic Assessment |
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| Fall | Injury, poisoning and procedural complications | Systematic Assessment |
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| Femoral neck fracture | Injury, poisoning and procedural complications | Systematic Assessment |
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| Cardiac arrest | Cardiac disorders | Systematic Assessment |
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| Cardio-respiratory arrest | Cardiac disorders | Systematic Assessment |
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| Aspartate aminotransferase increased | Investigations | Systematic Assessment |
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| Ejection fraction decreased | Investigations | Systematic Assessment |
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| Decreased appetite | Metabolism and nutrition disorders | Systematic Assessment |
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| Dehydration | Metabolism and nutrition disorders | Systematic Assessment |
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| Hyponatraemia | Metabolism and nutrition disorders | Systematic Assessment |
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| Drug-induced liver injury | Hepatobiliary disorders | Systematic Assessment |
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| Hepatobiliary disease | Hepatobiliary disorders | Systematic Assessment |
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| Bone marrow infiltration | Blood and lymphatic system disorders | Systematic Assessment |
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| Fatigue | General disorders | Systematic Assessment |
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| Pathological fracture | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Renal impairment | Renal and urinary disorders | Systematic Assessment |
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| Vasculitis | Vascular disorders | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | Systematic Assessment |
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| Dry mouth | Gastrointestinal disorders | Systematic Assessment |
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| Stomatitis | Gastrointestinal disorders | Systematic Assessment |
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| Gastrooesophageal reflux disease | Gastrointestinal disorders | Systematic Assessment |
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| Oral pain | Gastrointestinal disorders | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | Systematic Assessment |
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| Dysphagia | Gastrointestinal disorders | Systematic Assessment |
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| Abdominal pain upper | Gastrointestinal disorders | Systematic Assessment |
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| Dyspepsia | Gastrointestinal disorders | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Epistaxis | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Dyspnoea | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Dysphonia | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Productive cough | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Hypoxia | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Nasal congestion | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Nasal dryness | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Upper-airway cough syndrome | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Fatigue | General disorders | Systematic Assessment |
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| Asthenia | General disorders | Systematic Assessment |
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| Mucosal inflammation | General disorders | Systematic Assessment |
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| Pyrexia | General disorders | Systematic Assessment |
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| Chills | General disorders | Systematic Assessment |
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| Oedema peripheral | General disorders | Systematic Assessment |
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| Facial pain | General disorders | Systematic Assessment |
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| Swelling face | General disorders | Systematic Assessment |
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| Hypophosphataemia | Metabolism and nutrition disorders | Systematic Assessment |
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| Decreased appetite | Metabolism and nutrition disorders | Systematic Assessment |
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| Hypokalaemia | Metabolism and nutrition disorders | Systematic Assessment |
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| Hypocalcaemia | Metabolism and nutrition disorders | Systematic Assessment |
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| Dehydration | Metabolism and nutrition disorders | Systematic Assessment |
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| Hyperglycaemia | Metabolism and nutrition disorders | Systematic Assessment |
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| Hypomagnesaemia | Metabolism and nutrition disorders | Systematic Assessment |
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| Hyponatraemia | Metabolism and nutrition disorders | Systematic Assessment |
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| Dry skin | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Rash maculo-papular | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Alopecia | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Dermatitis acneiform | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Pruritus | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Skin lesion | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Palmar-plantar erythrodysaesthesia syndrome | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Erythema | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Hair colour changes | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Night sweats | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Headache | Nervous system disorders | Systematic Assessment |
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| Dysgeusia | Nervous system disorders | Systematic Assessment |
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| Dizziness | Nervous system disorders | Systematic Assessment |
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| Neuralgia | Nervous system disorders | Systematic Assessment |
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| Peripheral sensory neuropathy | Nervous system disorders | Systematic Assessment |
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| Taste disorder | Nervous system disorders | Systematic Assessment |
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| Pneumonia | Infections and infestations | Systematic Assessment |
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| Urinary tract infection | Infections and infestations | Systematic Assessment |
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| Rash pustular | Infections and infestations | Systematic Assessment |
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| Oral candidiasis | Infections and infestations | Systematic Assessment |
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| Candida infection | Infections and infestations | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | Systematic Assessment |
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| Weight decreased | Investigations | Systematic Assessment |
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| Aspartate aminotransferase increased | Investigations | Systematic Assessment |
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| Alanine aminotransferase increased | Investigations | Systematic Assessment |
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| Platelet count decreased | Investigations | Systematic Assessment |
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| Neutrophil count increased | Investigations | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Pain in extremity | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Insomnia | Psychiatric disorders | Systematic Assessment |
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| Anxiety | Psychiatric disorders | Systematic Assessment |
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| Depression | Psychiatric disorders | Systematic Assessment |
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| Vision blurred | Eye disorders | Systematic Assessment |
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| Dry eye | Eye disorders | Systematic Assessment |
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| Photophobia | Eye disorders | Systematic Assessment |
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| Hypertension | Vascular disorders | Systematic Assessment |
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| Infusion related reaction | Injury, poisoning and procedural complications | Systematic Assessment |
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| Anaemia | Blood and lymphatic system disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Chief Medical Officer | Ayala Pharmaceuticals | +1-857-444-0553 | info@ayalapharma.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Oct 18, 2022 | Dec 4, 2023 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D003528 | Carcinoma, Adenoid Cystic |
| ID | Term |
|---|---|
| D000230 | Adenocarcinoma |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
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| >=65 years |
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| Male |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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| Netherlands |
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| United States |
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| United Kingdom |
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| Israel |
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| France |
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| Spain |
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| Participants |
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