Ensayos clínicos

Inclusion Criteria: 

• Age >18 years old.
• 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.
• Evidence of radiographic or clinical disease progression within 6-months of signing informed consent; newly diagnosed metastatic patients will be allowed.
• Patients must have FFPE tissue available (please refer to Laboratory Manual for number of slides required). Archived7 (within 3 years) or fresh core or punch needle biopsied are acceptable.
• 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.
• 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.
• Male and/or Female: Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of investigational product. An extension up to 72 hours is permissible in situations where results cannot be obtained within the standard 24-hour window.
• WOCBP must agree to follow method(s) of contraception for the duration of the treatment with AL101 plus post-treatment completion based on country-specific requirements. Refer to Appendix E for country-specific requirements on contraception language.
• Men who are sexually active with WOCBP must agree to method(s) of contraception for the duration of treatment with AL101 plus post-treatment completion based on country-specific requirements. Refer to Appendix E for country-specific requirements on contraception language.
• apable of giving signed informed consent which includes compliance with the requirementsand restriction listed in the informed consent form (ICF) and in this protocol.

Exclusion Criteria: 

• Diagnosed with a malignancy in the past 2 years. However, patients with the following diagnoses may enroll as long as there is no current evidence of disease:
  • Non-melanoma skin cancers;
  • Melanoma in situ;
  • Localized cancer of the prostate with current prostate-specific antigen of <0.1 ng/mL;
  • Treated thyroid cancer;
  • Treated cervical carcinoma in situ;
  • Treated ductal/lobular carcinoma in situ of the breast.
• Current or recent (within 2 months of investigational product administration) gastrointestinal disease such as disorders that increase the risk of diarrhea, such as inflammatory bowel disease. Non-chronic conditions (e.g., infectious diarrhea) that are completely resolved for at least 2 weeks prior to starting investigational product are not exclusionary.
• Evidence of uncontrolled, active infection, requiring systemic anti-bacterial, anti-viral or anti-fungal therapy ≤7 days prior to administration of investigational product such as known active infection with hepatitis B, hepatitis C (HCV), or human immunodeficiency virus (HIV) at Screening (e.g., positive HIV, HBsAg, HCV RNA at screening).
• 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.
• 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 patient associated with his or her participation in the study.
• Female patients who are pregnant or breastfeeding.
• Completed palliative radiation therapy < 7 days prior to initiating investigational product.
• Prior treatment with gamma secretase inhibitors. Prior treatment with anti-Notch antibodies may be allowed upon discussion with the Sponsor’s medical monitor.
• 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, Prior treatment with incestigational monoclonal antibody will be reviewed case-by-case by the sponsor.