A study of investigational medicinal product AL101 in adults who have adenoid cystic carcinoma, and a specific genetic alteration in a gene called Notch, that has come back or did not get better with a previous therapy

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 87

Inclusion Criteria

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. Archived (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 and measurable by CT or MRI as per modified MDA Criteria.
6. Resolution of clinically significant toxicities related to prior therapy to CTCAE v5.0 = Grade 1, except for sensory neuropathy with resolution to = Grade 2 and alopecia.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 72
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 15

Exclusion Criteria

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 enrolment 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 judgement, 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 investigational product.
8. Prior treatment with gamma secretase inhibitors. .
9. Patients treated with a nucleoside analogue within 6 months prior to administration of investigational product.
10. 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.
11. Eastern Cooperative Oncology Group (ECOG) performance status =2.
12. Abnormal organ and marrow function
13. 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.
14. Mean QT interval corrected for heart rate using Fridericia’s formula (QTcF) =480 msec.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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