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

NCT04461600 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: AL-TNBC-01
• Study Type: interventional
• Target: 18
• Locations: 5 countries
• Sites: 29

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

Keywords

TNBC, Notch activated

Outcome Measures

Primary Outcomes (1)

• 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.

  12 month

Secondary Outcomes (2)

• Clinical Benefit Response Rate (CBR)

  12 month

• Duration of Response (DOR) by Investigator Review Based on RECIST v1.1

  12 month

Study Arms (1)

AL101

EXPERIMENTAL

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

Drug: AL101

Interventions

AL101 DRUG

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

AL101

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male of female subjects who are at least 18 years of age (inclusive) at the time of signing the Informed Consent Form (ICF).
• Have at least one measurable lesion per RECIST v1.1.
• 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.
• 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.
• 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+
• 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.
• Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test.

You may not qualify if:

• 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.
• BC that, in the opinion of the investigator, is considered amenable to potentially curative treatment.
• Symptomatic central nervous system (CNS) metastases.
• 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.
• 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.
• Peripheral neuropathy Grade 2 for at least 14 days prior to first dose of IP.
• 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).
• 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.
• Eastern Cooperative Oncology Group (ECOG) performance status ≥2.
• Abnormal organ and marrow function defined as:
• neutrophils \<1000/mm3,
• platelet count \<75,000/mm3,
• hemoglobin \<8 g/dL,
• total bilirubin \>1.5 upper limit of normal (ULN) (except known Gilbert's syndrome whereby the total bilirubin must be \< 5 mg/dL),
• aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \>2.5 ULN OR \>5 ULN for subjects with liver metastases,

Sponsors & Collaborators

• Ayala Pharmaceuticals, Inc,: lead

Study Sites (29)

Banner MD Anderson Cancer Center

Gilbert, Arizona, 85234, United States

Location

Mayo Clinic

Phoenix, Arizona, 85054, United States

Location

University of California at San Francisco

San Francisco, California, 94158, United States

Location

University of Colorado

Aurora, Colorado, 80045, United States

Location

Mayo Clinic

Jacksonville, Florida, 32224, United States

Location

Comprehensive Hematology Oncology

St. Petersburg, Florida, 33709, United States

Location

H. Lee Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

The University of Chicago

Chicago, Illinois, 60637, United States

Location

Carle Clinic

Urbana, Illinois, 61801, United States

Location

University of Louisville- James Brown Cancer Center

Louisville, Kentucky, 40202, United States

Location

Maryland Oncology Hematology

Columbia, Maryland, 20144, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Central Cancer Care

Bolivar, Missouri, 63613, United States

Location

Memorial Sloan Kettering Cancer Center (MSKCC)

New York, New York, 10065, United States

Location

University Health Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

Charleston Oncology

Charleston, South Carolina, 29414, United States

Location

Institut Jules Bordet

Brussels, Belgium

Location

UZ Leuven

Leuven, 3000, Belgium

Location

Rambam Medical Center

Haifa, 31096, Israel

Location

Shaare Zedek Hospital

Jerusalem, 9103102, Israel

Location

Hadassah Medical Center

Jerusalem, 91120, Israel

Location

Rabin Medical Center

Petah Tikva, 49100, Israel

Location

Kaplan Medical Center

Rehovot, 7661041, Israel

Location

Vall d'Hebron University Hospital

Barcelona, 8035, Spain

Location

Institut Català d'Oncologia

Barcelona, 8908, Spain

Location

Hospital Clinico Universitario Virgen de la Victoria

Málaga, 29010, Spain

Location

The Christie Hospital

Manchester, England, M204BX, United Kingdom

Location

University Hospital of Edinburgh

Edinburgh, Scotland, EH42XR, United Kingdom

Location

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Ayala Pharmaceuticals

info@ayalapharma.com

+1-857-444-0553

Study Officials

• Andres Gutierrez, MD, PhD

  Executive Vice President & Chief Medical Officer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 29, 2020
• First Posted: July 8, 2020
• Study Start: August 14, 2020
• Primary Completion: March 23, 2022
• Study Completion: October 11, 2022
• Last Updated: February 12, 2024
• Results First Posted: February 12, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (17); IL (5); BE (2); ES (3); GB (2)