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

NCT ID: NCT04461600

Last Updated: 2024-02-12

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-08-14
• Study Completion Date: 2022-10-11

Brief Summary

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.

Conditions

Triple Negative Breast Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

AL101

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

Group Type: EXPERIMENTAL

AL101

Intervention Type: DRUG

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

Interventions

AL101

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Male of female subjects who are 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+

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. Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test.

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.

2. BC that, in the opinion of the investigator, is considered amenable to potentially curative treatment.

3. Symptomatic central nervous system (CNS) metastases.

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.

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. Eastern Cooperative Oncology Group (ECOG) performance status ≥2.

10. Abnormal organ and marrow function defined as:

1. neutrophils <1000/mm3,

2. platelet count <75,000/mm3,

3. hemoglobin <8 g/dL,

4. total bilirubin >1.5 upper limit of normal (ULN) (except known Gilbert's syndrome whereby the total bilirubin must be < 5 mg/dL),

5. aspartate aminotransferase (AST) and alanine aminotransferase (ALT) >2.5 ULN OR >5 ULN for subjects with liver metastases,

6. creatinine clearance (CrCl) <50 mL/min (calculation of CrCl will be based on acceptable institution standard),

7. uncontrolled triglyceride ≥Grade 2 elevations per CTCAE v5.0 (>300 mg/dL or >3.42 mmol/L).

11. 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.

12. Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥480 msec.

13. Completed palliative radiation therapy < 7 days prior to initiating IP.

14. Prior treatment with gamma secretase inhibitors.

15. Last chemotherapy, biologic, or investigational therapy agent at least 4 weeks or 5 half-lives (whichever is shorter) prior to initiating IP; at least 6 weeks if the last regimen included BCNU or mitomycin C. Prior treatment with investigational monoclonal antibody will be reviewed case-by-case by the Sponsor.

16. Receiving chronic systemic steroid therapy (in dosing exceeding 10 mg/day of prednisone or equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of IP. The use of physiologic doses of corticosteroids may be approved after consultation with the Sponsor.

17. Use of strong inhibitors of CYP3A4 within 1 week or 5 half-lives (whichever is longer) or strong inducers of CYP3A4 within 2 weeks or 5 half-lives (whichever is longer).

18. Life expectancy is less than 3 months.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ayala Pharmaceuticals, Inc,

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Andres Gutierrez, MD, PhD

Role: STUDY_DIRECTOR

Executive Vice President & Chief Medical Officer

Locations

Banner MD Anderson Cancer Center

Gilbert, Arizona, United States

Mayo Clinic

Phoenix, Arizona, United States

University of California at San Francisco

San Francisco, California, United States

University of Colorado

Aurora, Colorado, United States

Mayo Clinic

Jacksonville, Florida, United States

Comprehensive Hematology Oncology

St. Petersburg, Florida, United States

H. Lee Moffitt Cancer Center

Tampa, Florida, United States

The University of Chicago

Chicago, Illinois, United States

Carle Clinic

Urbana, Illinois, United States

University of Louisville- James Brown Cancer Center

Louisville, Kentucky, United States

Maryland Oncology Hematology

Columbia, Maryland, United States

University of Michigan

Ann Arbor, Michigan, United States

Mayo Clinic

Rochester, Minnesota, United States

Central Cancer Care

Bolivar, Missouri, United States

Memorial Sloan Kettering Cancer Center (MSKCC)

New York, New York, United States

University Health Cleveland Medical Center

Cleveland, Ohio, United States

Charleston Oncology

Charleston, South Carolina, United States

Institut Jules Bordet

Brussels, , Belgium

UZ Leuven

Leuven, , Belgium

Rambam Medical Center

Haifa, , Israel

Shaare Zedek Hospital

Jerusalem, , Israel

Hadassah Medical Center

Jerusalem, , Israel

Rabin Medical Center

Petah Tikva, , Israel

Kaplan Medical Center

Rehovot, , Israel

Vall d'Hebron University Hospital

Barcelona, , Spain

Institut Català d'Oncologia

Barcelona, , Spain

Hospital Clinico Universitario Virgen de la Victoria

Málaga, , Spain

The Christie Hospital

Manchester, England, United Kingdom

University Hospital of Edinburgh

Edinburgh, Scotland, United Kingdom

Countries

United States; Belgium; Israel; Spain; United Kingdom

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

AL-TNBC-01

Identifier Type: -

Identifier Source: org_study_id