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

• Sponsor: Ayala Pharmaceuticals, Inc, (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT04461600
• Collaborator: (none)
• Enrollment: 67
• Locations: 29
• Arm: 1
• Anticipated Duration (Months): 39.6
• Patients Per Site: 2.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Triple Negative Breast Cancer	Drug: AL101	Phase 2

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 67 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Multi-center, Open-label, Single Arm Study of AL101 Monotherapy in Patients With Notch Activated Triple Negative Breast Cancer
• Actual Study Start Date: Aug 14, 2020
• Anticipated Primary Completion Date: Nov 1, 2023
• Anticipated Study Completion Date: Dec 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AL101 AL101 is an inhibitor of gamma secretase-mediated Notch signaling.	Drug: AL101; AL101 is an inhibitor of gamma secretase-mediated Notch signaling.

Outcome Measures

Primary Outcome Measures

1. Overall response rate (ORR) [12 month]

   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

1. Clinical benefit response rate (CBR) [12 month]

   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

2. Duration of response (DOR) by investigator review based on RECIST v1.1 [12 month]

3. Progression free survival (PFS) [12 month]

4. Proportion of subjects who have Progression free survival (PFS) at 6 months [6 month]

5. Overall survival (OS) [12 month]

6. Quality of life (QoL)-QLQ-C30 [12 month]

   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.

7. Quality of life (QoL)- QLQ-BR45 [12 month]

   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.

8. 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. [12 month]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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:

11. neutrophils <1000/mm3,

12. platelet count <75,000/mm3,

13. hemoglobin <8 g/dL,

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

15. aspartate aminotransferase (AST) and alanine aminotransferase (ALT) >2.5 ULN OR

5 ULN for subjects with liver metastases,

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

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

3. 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.

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

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

6. Prior treatment with gamma secretase inhibitors.

7. 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.

8. 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.

9. 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).

10. Life expectancy is less than 3 months.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Banner MD Anderson Cancer Center	Gilbert	Arizona	United States	85234
2	Mayo Clinic	Phoenix	Arizona	United States	85054
3	University of California at San Francisco	San Francisco	California	United States	94158
4	University of Colorado	Aurora	Colorado	United States	80045
5	Mayo Clinic	Jacksonville	Florida	United States	32224
6	Comprehensive Hematology Oncology	Saint Petersburg	Florida	United States	33709
7	H. Lee Moffitt Cancer Center	Tampa	Florida	United States	33612
8	The University of Chicago	Chicago	Illinois	United States	60637
9	Carle Clinic	Urbana	Illinois	United States	61801
10	University of Louisville- James Brown Cancer Center	Louisville	Kentucky	United States	40202
11	Maryland Oncology Hematology	Columbia	Maryland	United States	20144
12	University of Michigan	Ann Arbor	Michigan	United States	48109
13	Mayo Clinic	Rochester	Minnesota	United States	55905
14	Central Cancer Care	Bolivar	Missouri	United States	63613
15	Memorial Sloan Kettering Cancer Center (MSKCC)	New York	New York	United States	10065
16	University Health Cleveland Medical Center	Cleveland	Ohio	United States	44106
17	Charleston Oncology	Charleston	South Carolina	United States	29414
18	Institut Jules Bordet	Brussels		Belgium
19	UZ Leuven	Leuven		Belgium	3000
20	Rambam Medical Center	Haifa		Israel	31096
21	Shaare Zedek Hospital	Jerusalem		Israel	9103102
22	Hadassah Medical Center	Jerusalem		Israel	91120
23	Rabin Medical Center	Petah Tikva		Israel	49100
24	Kaplan Medical Center	Reẖovot		Israel	7661041
25	Vall d'Hebron University Hospital	Barcelona		Spain	8035
26	Institut Català d'Oncologia	Barcelona		Spain	8908
27	Hospital Clinico Universitario Virgen de la Victoria	Málaga		Spain	29010
28	The Christie Hospital	Manchester	England	United Kingdom	M204BX
29	University Hospital of Edinburgh	Edinburgh	Scotland	United Kingdom	EH42XR

Sponsors and Collaborators

• Ayala Pharmaceuticals, Inc,

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Ayala Pharmaceuticals, Inc,
• ClinicalTrials.gov Identifier: NCT04461600
• Other Study ID Numbers: AL-TNBC-01
• First Posted: Jul 8, 2020
• Last Update Posted: Apr 1, 2022
• Last Verified: Oct 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Ayala Pharmaceuticals, Inc,: TNBC, Notch activated
• Additional relevant MeSH terms: Breast Neoplasms; Triple Negative Breast Neoplasms

Study Results

No Results Posted as of Apr 1, 2022