Notch Activated Recurrent or Metastatic Triple Negative Breast Cancer MedDRA version: 20.0 Level: PT Classification code 10075566 Term: Triple negative breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Ayala Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
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 =65 years) yes F.1.3.1 Number of subjects for this age range 15
Exclusion criteria
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 1.5 x upper limit of normal (ULN) (except known Gilbert’s syndrome whereby the total bilirubin must be 2.5 x ULN OR >5 x ULN for subjects with liver metastases, f. serum creatinine > ULN and creatinine clearance (CrCl) 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 inhibito
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of AL101 monotherapy in subjects with Notch-activated recurrent or metastatic TNBC;Secondary Objective: - Efficacy - Secondary - To evaluate the safety and tolerability of AL101 monotherapy in subjects with recurrent or metastatic TNBC;Primary end point(s): Proportion of subjects who demonstrate an overall response rate (ORR), defined as partial response (PR) + complete response (CR) as assessed by investigator based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1;Timepoint(s) of evaluation of this end point: Throughout the course of the study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Clinical benefit response rate (CBR) defined as CR +PR + stable disease (SD) by investigator review based on RECIST v1.1 - Duration of response (DOR) by investigator review based on RECIST v1.1 - Progression free survival (PFS) - Proportion of subjects who have PFS at 6 months - Overall survival (OS) - Quality of life (QoL) as determined by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30 questions (EORTC QLQ-C30) and Breast Cancer 45 questions (EORTC QLQ-BR45) - Frequency, duration and severity of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) - Incidence of clinically significant abnormalities in laboratory parameters, electrocardiograms (ECGs), vital signs and physical examination.;Timepoint(s) of evaluation of this end point: Throughout the course of the study | — |
Countries
Belgium, France, Israel, Netherlands, Spain, United Kingdom, United States
Contacts
Public ContactClinical Trial Information
Ayala Pharmaceuticals, Inc.
Outcome results
None listed