Progressing desmoid tumors MedDRA version: 20.1 Level: PT Classification code 10059352 Term: Desmoid tumour System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: AL102
Product Code: BMS-986115
Pharmaceutical Form: Capsule
INN or Proposed INN: AL102
Current Sponsor code: AL102
Other descriptive name: (2R,3S)-N1-[(3S)-5-(3-Fluorophenyl)-2,3-dihydro
Sponsors
Ayala Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Part A 1. At least 18 years of age (inclusive) at the time of signing the ICF. 2. Histologically confirmed desmoid tumor (aggressive fibromatosis) by local pathologist (prior to informed consent) that has progressed by = 20% as measured by RECIST v1.1 within 12 months of the screening visit scan. 3. At least 1 measurable lesion amenable to volume measurements by MRI at screening 4. One of the following: • Treatment naïve subjects whose disease is not amenable to surgery without the risk of significant morbidity; OR • Recurrent/refractory disease following at least one line of therapy (including surgery, radiation, or systemic therapy). 5. A desmoid tumor in which continued progressive disease will not result in immediate significant risk to the subject. 6. Agrees to provide formalin-fixed paraffin embedded (FFPE) archival or fresh tumor tissue. 7. Must be able to swallow whole capsules with no GI condition affecting absorption; nasogastric or G-tube administration is not allowed. 8. Male or female subjects. 9. Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [hCG]) within 24 hours prior to the start of investigational product (IP). An extension up to 72 hours is permissible in situations where results cannot be obtained within the standard 24 hour window. 10. WOCBP and men who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of the treatment with IP plus 120 days post-treatment completion. Contraception methods should be consistent with local regulations. 11. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and in this protocol. Part B 1. =12 years of age (inclusive) and = 40 kg at the time of signing the ICF. 2. Histologically confirmed desmoid tumor (aggressive fibromatosis) by local pathologist (prior to informed consent) that has progressed by = 20% as measured by RECIST v1.1 within 12 months of the screening visit scan. 3. Evidence of measurable disease by CT/MRI scan. Measurable lesions are defined according to RECIST v1.1. 4. One of the following: • Treatment naïve subjects whose disease is not amenable to surgery without the risk of significant morbidity; OR • Recurrent/refractory disease following at least one line of therapy (including surgery, radiation, or systemic therapy). 5. A desmoid tumor in which continued progressive disease will not result in immediate significant risk to the subject. 6. Agrees to provide FFPE archival or fresh tumor tissue. 7. Must be able to swallow whole capsules with no GI condition affecting absorption; nasogastric or G-tube administration is not allowed. Gender and Reproductive Considerations 8. Male or female subjects. 9. WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of hCG) within 24 hours prior to the start of IP. An extension up to 72 hours is permissible in situations where results cannot be obtained within the standard 24-hour window. 10. WOCBP and men who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of the treatment with IP plus 120 days post-treatment completion. Contraception methods should be consistent with local regulations. 11. Subject and/or legally authorized representative (i.e. parent/gua
Exclusion criteria
Exclusion criteria: Part A 1. Diagnosed with a malignancy in the past 2 years. However, subjects with the following diagnoses may enroll as long as there is no current evidence of disease: • Non-melanoma skin cancers • Melanoma in situ • Treated thyroid cancer • Treated cervical carcinoma in situ • Early-stage prostate cancer that has undergone definitive treatment or under active surveillance 2. Current or recent (within 2 months of IP administration) GI disease or disorders that increase the risk of diarrhea, such as inflammatory bowel disease and Crohn’s disease 3. Evidence of uncontrolled, active infection, requiring systemic anti-bacterial, anti-viral or anti-fungal therapy =7 days prior to administration of IP 4. Myocardial infarction within 6 months prior to enrollment, greater than Class 1 angina pectoris, or has NYHA Class III or IV heart failure, symptomatic ventricular arrhythmias, sustained ventricular tachycardia, TdP, the long QT syndrome, pacemaker dependence, or electrocardiographic evidence of acute ischemia 5. History of additional risk factors for TdP 6. Unstable or severe uncontrolled medical condition or any important medical illness or abnormal laboratory finding 7. Pregnant or breastfeeding or expecting to conceive children within the projected duration of the study 8. ECOG performance status =2 9. Abnormal organ and marrow function at Screening defined as: a. Neutrophils 1.5x ULN (except known Gilbert’s syndrome >3x ULN) f. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) >2.5x ULN g. Serum creatinine > ULN and creatinine clearance (CrCl) 300 mg/dL or >3.42 mmol/L) 10. ECG Exclusions a. Mean QT interval corrected for heart rate using Fridericia’s formula (QTcF) =450 msec b. QRS duration > 110 ms c. PR interval > 240 ms d. Marked ST-T wave abnormalities which would make it difficult to measure the QT interval 11. Any treatments for desmoid tumors within 4 weeks prior to first dose 12. Chronic NSAIDs for the treatment of desmoid tumors within 4 weeks of first dose 13. Prior treatment with GSI or other agents targeting the Notch pathway 14. Use of strong inhibitors of CYP3A4 or strong inducers of CYP3A4 18. Contraindication to MRI Part B 1. Diagnosed with a malignancy in the past 2 years. However, subjects with the following diagnoses may enroll as long as there is no current evidence of disease: • Non-melanoma skin cancers • Melanoma in situ • Treated thyroid cancer • Treated cervical carcinoma in situ • Early-stage prostate cancer that has undergone definitive treatment or under active surveillance 2. Current or recent (within 2 months of IP administration) GI disease or disorders that increase the risk of diarrhea, such as inflammatory bowel disease and Crohn’s disease 3. Evidence of uncontrolled, active infection, requiring systemic anti-bacterial, anti-viral or anti-fungal therapy =7 days prior to administration of IP 4. Myocardial infarction within 6 months prior to enrollment, greater than Class 1 angina pectoris, or has NYHA Class III or IV heart failure, symptomatic ventricular arrhythmias, sustained ventricular tachycardia, TdP, the long QT syndrome, pacemaker dependence
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part A: To evaluate the safety and tolerability of AL102 in subjects with progressive desmoid tumors Part B: To evaluate effects of AL102 on disease progression in subjects with progressive desmoid tumors;Primary end point(s): Part A: Frequency, duration and severity of TEAEs ans SAEs; time to treatment discontinuation due to TEAE Part B: Progression free survival;Timepoint(s) of evaluation of this end point: Part A: throughout study duration Part B: from randomization until the date of assessment of progression or death by any cause;Secondary Objective: Part A: To assess the effects of AL102 on desmoid tumor size in subjects with progressive desmoid tumors Part B: 1. To evaluate additional effects of AL102 on tumor response; 2. To evaluate effects of AL102 on quality of life; 3. To evaluate the safety and tolerability of AL102 in subjects with progressive desmoid tumors | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Part A: from beseline to week 16 Part B: 1, 3-6. baseline and throughout study duration 2. time from CR or PR until the earlier first documentation of disease progression or death from any cause;Secondary end point(s): Part A: change from baseline to week 16 in tumor volume Part B: 1. proportion of subjects with ORR; 2. duration of response; 3. change from baseline in quality of life; 4. change from baseline in pain assessment; 5. frequency, duration and severity of TEAEs and SAEs; 6. time to treatment discontinuation due to TEAE | — |
Countries
Australia, Austria, Belgium, Canada, France, Germany, Greece, Israel, Italy, Korea, Republic of, Netherlands, New Zealand, Poland, Spain, Taiwan, United Kingdom, United States
Contacts
Public ContactVP Regulatory Affairs
Ayala Pharmaceuticals, Inc.
Outcome results
None listed