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Triple Negative Breast CancerPhase 2TENACITYNCT04461600

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

A Phase 2 study testing AL101 in people with Triple Negative Breast Cancer, run by Ayala Pharmaceuticals, Inc, at 29 sites in 5 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Triple Negative Breast Cancer
What is being tested?
AL101
Could I receive a placebo?
No, everyone receives an active treatment
How many people
18 participants
Where
29 sitesin 5 countries
Study dates
14 Aug 2020to 11 Oct 2022
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
Show all 25Show fewer
  • 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,
  • creatinine clearance (CrCl) <50 mL/min (calculation of CrCl will be based on acceptable institution standard),
  • uncontrolled triglyceride ≥Grade 2 elevations per CTCAE v5.0 (>300 mg/dL or >3.42 mmol/L).
  • 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.
  • Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥480 msec.
  • Completed palliative radiation therapy < 7 days prior to initiating IP.
  • Prior treatment with gamma secretase inhibitors.
  • 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.
  • 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.
  • 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).
  • Life expectancy is less than 3 months.

Trial locations and contacts

29 sites in 5 countries.

29 sites in 5 countries

United States17 sites

  • University of Michigan

    Ann Arbor, Michigan, 48109

  • University of Colorado

    Aurora, Colorado, 80045

  • Central Cancer Care

    Bolivar, Missouri, 63613

  • Charleston Oncology

    Charleston, South Carolina, 29414

  • The University of Chicago

    Chicago, Illinois, 60637

  • University Health Cleveland Medical Center

    Cleveland, Ohio, 44106

  • Maryland Oncology Hematology

    Columbia, Maryland, 20144

  • Banner MD Anderson Cancer Center

    Gilbert, Arizona, 85234

  • Mayo Clinic

    Jacksonville, Florida, 32224

  • University of Louisville- James Brown Cancer Center

    Louisville, Kentucky, 40202

  • Memorial Sloan Kettering Cancer Center (MSKCC)

    New York, New York, 10065

  • Mayo Clinic

    Phoenix, Arizona, 85054

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • University of California at San Francisco

    San Francisco, California, 94158

  • Comprehensive Hematology Oncology

    St. Petersburg, Florida, 33709

  • H. Lee Moffitt Cancer Center

    Tampa, Florida, 33612

  • Carle Clinic

    Urbana, Illinois, 61801

Other trials in United States

Israel5 sites

  • Rambam Medical Center

    Haifa, 31096

  • Shaare Zedek Hospital

    Jerusalem, 9103102

  • Hadassah Medical Center

    Jerusalem, 91120

  • Rabin Medical Center

    Petah Tikva, 49100

  • Kaplan Medical Center

    Rehovot, 7661041

Other trials in Israel

Spain3 sites

  • Vall d'Hebron University Hospital

    Barcelona, 8035

  • Institut Català d'Oncologia

    Barcelona, 8908

  • Hospital Clinico Universitario Virgen de la Victoria

    Málaga, 29010

Other trials in Spain

Belgium2 sites

  • Institut Jules Bordet

    Brussels

  • UZ Leuven

    Leuven, 3000

Other trials in Belgium

United Kingdom2 sites

  • University Hospital of Edinburgh

    Edinburgh, Scotland, EH42XR

  • The Christie Hospital

    Manchester, England, M204BX

Other trials in United Kingdom

About this study

Official title: A Phase 2, Multi-center, Open-label, Single Arm Study of AL101 Monotherapy in Patients With Notch Activated Triple Negative Breast Cancer

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.

Being tested
AL101
Keywords
TNBC, Notch activated
Medical subject headings
Triple Negative Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AL101Drug

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

Study groups in NCT04461600
Study groupRoleWhat they receive
AL101ExperimentalThe study included a lead-in cohort with 6 subjects at 6mg AL101 weekly. 13 additional patients were treated with 4mg AL101 weekly.
Receives: Drug: AL101

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 12 month

Secondary outcomes (2)

  1. Clinical Benefit Response Rate (CBR)

    Clinical benefit response rate (CBR) is defined as complete response (CR) + partial response (PR) + stable disease (SD) by investigator review based on 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.

    Stable Disease (SD): Neither sufficient shrinkage (at least 30%) to qualify for PR nor sufficient increase (more than 20%) to qualify for PD, taking as reference the smallest sum diameters.

    Measured: 12 month

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

    Duration of response (DOR) is defined as the time from randomization to disease progression or death in patients who achieve complete or partial response.

    Measured: 12 month

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Jul 2020
  2. Study start14 Aug 2020
  3. Primary completion23 Mar 2022
  4. Study completion11 Oct 2022

Why it stopped: Sponsor's decision

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
18 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04461600
Sponsor's protocol ID
AL-TNBC-01
Acronym
TENACITY
Status last verified
Jan 2024
First submitted
29 Jun 2020
Last updated
12 Feb 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing AL101 in people with Triple Negative Breast Cancer, run by Ayala Pharmaceuticals, Inc, at 29 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 12 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 29 sites in United States, Israel, Spain, Belgium, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 12 Feb 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Response Rate (ORR) (time frame: 12 month). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04461600.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Feb 2024.

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