A Phase 2, Open-Label, multi-center Study of AL101 in patients with adenoid cystic carcinoma (ACC) bearing activating Notch mutations

Phase 2

Completed

Conditions: Adenoid cystic carcinoma
saliva gland cancer
10027655

Registration Number: NL-OMON49242

Lead Sponsor: Ayala Pharmaceuticals, Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 5

Inclusion Criteria

In order to be eligible for participation in this study, the patient must meet
all of the following:
1. Age >18 years old.
2. Histologically confirmed ACC with known NOTCH 1/2/3/4 activating mutation
that is
recurrent or metastatic, not amenable to potentially curative surgery or
radiotherapy.
3. Evidence of radiographic or clinical disease progression within 6-months of
signing informed
consent; newly diagnosed metastatic patients will be allowed.
4. Patients must have FFPE tissue available (please refer to laboratory manual
for number of
slides required). Archived5 (within 3 years) or fresh core or punch needle
biopsied are
acceptable.
5. Must have at least 1 target lesion that is measurable per RECIST v1.1 for
patients with nodal
or visceral metastasis. Patients with bone exclusive disease will also be
eligible after consultation and approval with Sponsor's Medical Monitor and
only if bone
lesions are evaluable by CT or MRI as per modified MDA Criteria. (see Table 9 in
Appendix C).
6. Resolution of clinically significant toxicities related to prior therapy to
National Cancer
Institute (NCI) - Common Terminology Criteria for Adverse Events (CTCAE v5.0)
<= Grade 1, except for sensory neuropathy with resolution to <= Grade 2 and
alopecia.

Exclusion Criteria

The patient must be excluded from participating in the study if meet any of the
following:
Medical Conditions
1. Diagnosed with a malignancy in the past 2 years.
2. Current or recent gastrointestinal disease. Nonchronic conditions that are
completely resolved for at least 2 weeks prior to starting investigational
product are not exclusionary.
3. Evidence of uncontrolled, active infection, requiring systemic
anti-bacterial, anti-viral or
anti-fungal therapy <=7 days prior to administration of investigational product
at Screening.
4. Symptomatic central nervous system (CNS) metastases. Patients with
asymptomatic CNS
metastases as well as those with previously treated CNS metastases are eligible
for
enrollment in the study if at least four weeks has elapsed since last whole
brain radiation
treatment or at least two weeks has elapsed since last focal radiation
treatment, steroid
therapy is not required, and the patient is deemed clinically stable by the
Investigator.
5. Unstable or severe uncontrolled medical condition or any important medical
illness or abnormal laboratory finding that would, in the investigator*s
judgment, increase the risk to the patient associated with his or her
participation in the study.
6. Female patients who are pregnant or breastfeeding.
7. Completed palliative radiation therapy < 7 days prior to initiating study
drug.
8. Prior treatment with gamma secretase inhibitors.
9. Last chemotherapy, biologic, or investigational therapy agent <4 weeks or 5
half-lives (whichever is shorter) prior to initiating investigational product;
6 weeks if the last regimen included BCNU or mitomycin C.
10. Eastern Cooperative Oncology Group (ECOG) performance status >=2.
11. Abnormal organ and marrow function defined as:
a. neutrophils <1500/mm3,
b. platelet count <100,000/mm3,
c. hemoglobin <9 g/dL,
d. total bilirubin >1.5 x upper limit of normal (ULN) (except known Gilbert's
syndrome),
e. aspartate aminotransferase (AST) and alanine aminotransferase (ALT) >2.5 x
ULN OR >5 x ULN for patients with liver metastases,
f. serum creatinine > ULN and creatinine clearance <50 mL/min (Calculation of
CrCl will be based on acceptable institution standard),
g. uncontrolled triglyceride =Grade 2 elevations per CTCAE v5.0 (>300 mg/dL or
>3.42 mmol/L)
12. Myocardial infarction within 6 months prior to enrollment or has NYHA Class
III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular
arrhythmias, or electrocardiographic evidence of acute ischemia or active
conduction system abnormalities.
13. Mean QT interval corrected for heart rate using Fridericia's formula (QTcF)
>=480 msec.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Objective response rate (ORR; CR and PR) by RECIST v1.1 as determined by an<br /><br>Independent Central Review (ICR). For patients with bone-exclusive disease, the<br /><br>modified MDA bone criteria will be used to access response.</p><br>

Secondary Outcome Measures