E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Adenoid cystic carcinoma is a rare type of cancer that can affect many different body sites |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10053231 |
E.1.2 | Term | Adenoid cystic carcinoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the clinical activity of AL101 using radiographic assessments and RECIST v1.1 in ACC patients with activating Notch mutations |
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E.2.2 | Secondary objectives of the trial |
To assess quality of life in ACC patients with activating Notch mutations To confirm safety and tolerability of AL101 in ACC patients with activating Notch mutations To obtain a set of population parameters and to identify covariates that affect systemic exposure to AL101 and metabolite(s) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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. |
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E.4 | Principal 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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Objective response rate (ORR; complete response [CR] and partial response [PR]) by RECIST v1.1 [ Time Frame: Up to 36 month ] |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Imaging and radiologic evaluation will be performed every 8 weeks during treatment period and then at 3 month intervals during long-term follow-up |
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E.5.2 | Secondary end point(s) |
Frequency, duration and severity of adverse events (AEs) and serious adverse events (SAEs); [ Time Frame: Up to 36 month ] Change from baseline in EORTC QLQ-C30 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Safety evaluations will be performed on D1, D8, D15 and D22 of each treatment cycle and 30 days post last study drug administration Quality of life questionnaire will be administered every 4 weeks before investigational product administration or receipt of radiological imaging results |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 8 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Canada |
France |
Germany |
Israel |
Italy |
Netherlands |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 10 |