Clinical Trials /

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

NCT04461600

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: AL-TNBC-01
  • NCT ID: NCT04461600

Conditions

  • Triple Negative Breast Cancer

Interventions

DrugSynonymsArms
AL101AL101

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
AL101ExperimentalAL101 is an inhibitor of gamma secretase-mediated Notch signaling.
  • AL101

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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall response rate (ORR)
Time Frame:12 month
Safety Issue:
Description:ORR is defined as partial response (PR) + complete response (CR) as assessed by investigator based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

Secondary Outcome Measures

Measure:Clinical benefit response rate (CBR)
Time Frame:12 month
Safety Issue:
Description: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
Measure:Duration of response (DOR) by investigator review based on RECIST v1.1
Time Frame:12 month
Safety Issue:
Description:
Measure:Progression free survival (PFS)
Time Frame:12 month
Safety Issue:
Description:
Measure:Proportion of subjects who have Progression free survival (PFS) at 6 months
Time Frame:6 month
Safety Issue:
Description:
Measure:Overall survival (OS)
Time Frame:12 month
Safety Issue:
Description:
Measure:Quality of life (QoL)-QLQ-C30
Time Frame:12 month
Safety Issue:
Description:The QLQ-C30 is composed of both multi-item scales and single-item measures. These include five functional scales, three symptom scales, a global health status / Quality of life scale, and six single items. Each of the multi-item scales includes a different set of items - no item occurs in more than one scale. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. Thus a high score for a functional scale represents a high / healthy level of functioning, a high score for the global health status / Quality of life represents a high Quality of life, but a high score for a symptom scale / item represents a high level of symptomatology / problems.
Measure:Quality of life (QoL)- QLQ-BR45
Time Frame:12 month
Safety Issue:
Description:Quality of life (QoL) as determined by European Organization for Research and Treatment of Cancer, by breast cancer quality of life questionnaire QLQ-BR45. QLQ-BR45 is a supplementary questionnaire module to be employed in conjunction with the QLQ-C30. The QLQ-BR45 incorporates nine multi-item scales to assess body image, sexual functioning, breast satisfaction, systemic therapy side,effects, arm symptoms, breast symptoms, endocrine therapy symptoms, skin mucosis symptoms, endocrine sexual symptoms. In addition, single items assess sexual enjoyment, future perspective and being upset by hair loss. All of the scales and single item measures range in score from 0 to 100. A high score for the functional scales and functional single items represents a high/healthy level of functioning, whereas a high score for the symptom scales and symptom item represents a high level of symptomatology or problems.
Measure:Frequency, duration and severity of treatment-emergent adverse events and serious adverse events in subjects with recurrent or metastatic Triple Negative Breast Cancer receiving AL101 monotherapy.
Time Frame:12 month
Safety Issue:
Description:Frequency, duration and severity of treatment-emergent adverse events and serious adverse events. The incidence of clinically significant abnormalities in laboratory parameters, electrocardiograms, vital signs and physical examination will be used to describe treatment-emergent adverse events and serious adverse events.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Ayala Pharmaceuticals, Inc,

Trial Keywords

  • TNBC, Notch activated

Last Updated

October 6, 2020