A study of investigational medicinal product AL101 in adults with breast cancer

Phase 1

Conditions: otch Activated Recurrent or Metastatic Triple Negative Breast Cancer
MedDRA version: 20.0Level: PTClassification code 10075566Term: Triple negative breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2020-001979-33-GB

Lead Sponsor: Ayala Pharmaceuticals, Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 73

Inclusion Criteria

1. At least 18 years of age (inclusive) at the time of signing the Informed Consent Form (ICF).
2. Have at least one measurable lesion per RECIST v1.1.
3. Have formalin-fixed paraffin-embedded (FFPE) tissue available from a metastatic lesion; a tumor block or 25 unstained slides from an archived (within 2 years) or fresh tumor samples (core or punch needle biopsy) are acceptable.
4. Documented tumor progression following no more than 3 lines of systemic chemotherapy, PARP inhibitor therapy or immunotherapy for metastatic disease, as appropriate. Of note, neoadjuvant and adjuvant therapy will not count as prior lines of therapy.
5. Histologically confirmed diagnosis of inoperable locally advanced or metastatic TNBC defined as ER and progesterone receptor staining <10%, and HER2-negative defined as IHC 0 to 1+. Note, if IHC is equivocal then do fluorescence in situ hybridization (FISH) or in situ hybridization (ISH); negative will be acceptable. Note: if FISH or ISH is equivocal then further assessment is allowed with Sponsor written approval.
6. Documented Notch activation from tumor biopsy results from within the last 2 years from a commercially available NGS assay, LDT or other validated IUO clinical trial assay.
7. Female or Male subjects.
8. Women of childbearing potential (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 and must agree to have a pregnancy test at least every cycle (4 weeks). An extension up to 72 hours is permissible in situations where results cannot be obtained within the standard 24-hour window. Contraception use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
9. WOCBP must agree to use a highly effective birth control during the study (prior to the first dose with AL101 and for 120 days after the last dose), if conception is possible during this interval. Female subjects are considered to not be of childbearing potential if they have a history of hysterectomy or are post-menopausal defined as no menses for 12 months without an alternative medical cause.
10. Male subjects with partners who are WOCBP should use a combination of the methods specified in Section 10.4 for the women along with a male condom during the study and for 120 days after the last dose of IP, unless permanently sterile by bilateral orchidectomy.
11. Capable of giving signed informed consent form (ICF) which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 58
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 15

Exclusion Criteria

1. A known additional malignancy that is progressing or requires active treatment that is considered medically active and may interfere in the ability to detect responses in this subject. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that have undergone potentially curative therapy or in situ cervical cancer. Any exceptions should be discussed with the Sponsor’s Medical Monitor.
2. BC that, in the opinion of the investigator, is considered amenable to potentially curative treatment.
3. Symptomatic central nervous system (CNS) metastases. Subjects with asymptomatic CNS metastases as well as those with previously treated CNS metastases are eligible for enrollment in the study if at least 28 days has elapsed since definitive treatment (either surgery, whole brain radiotherapy, stereotactic radiation), steroid therapy is either not required or dose has been weaned off over last 14 days, and the subject is deemed
clinically stable by the investigator.
4. Current or recent (within 2 months of IP administration) gastrointestinal (GI) disease or disorders that increase the risk of diarrhea, such as inflammatory bowel disease and Crohn’s disease. Non-chronic conditions (e.g., infectious diarrhea) that are completely resolved for at least 2 weeks prior to starting IP are not exclusionary.
5. Developed immune-mediated colitis with immunotherapy unless resolved to G1 or lower and without requirement of steroid treatment for at least 14 days prior to first dose of IP.
6. Peripheral neuropathy = Grade 2 for at least 14 days prior to first dose of IP.
7. Evidence of uncontrolled, active infection, requiring systemic anti-bacterial, anti-viral or anti-fungal therapy =7 days prior to administration of IP such as known active infection with hepatitis B, hepatitis C, or human immunodeficiency virus (HIV).
8. Unstable or severe uncontrolled medical condition (e.g., unstable cardiac or pulmonary function or uncontrolled diabetes) or any important medical illness or abnormal laboratory finding that would, in the investigator’s judgment, increase the risk to the subject associated with his or her participation in the study.
9. Pregnant or breastfeeding or expecting to conceive children within the projected duration of the study.
10. Eastern Cooperative Oncology Group (ECOG) performance status =2.
11. Abnormal organ and marrow function defined as:
a. neutrophils <1000/mm3,
b. platelet count <75,000/mm3,
c. hemoglobin <8 g/dL,
d. total bilirubin >1.5 x upper limit of normal (ULN) (except known Gilbert’s syndrome whereby the total bilirubin must be < 5 mg/dL),
e. aspartate aminotransferase (AST) and alanine aminotransferase (ALT) >2.5 x ULN OR >5 x ULN for subjects with liver metastases,
f. serum creatinine > ULN and creatinine clearance (CrCl) <50 mL/min (calculation of CrCl will be based on acceptable institution standard),
g. uncontrolled triglyceride =Grade 2 elevations per CTCAE v5.0 (>300 mg/dL or >3.42 mmol/L).
12. Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
13. Mean QT interval corrected for heart rate using Fridericia’s formula (QTcF) =480 msec.
14. Completed palliative radiation therapy < 7 days prior to initiating IP.
15. Prior treatment with gamma secretase inhibit

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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