IDH1 Inhibitor AB-218 in Patients With Advanced IDH1 Mutant Cholangiocarcinoma and Other Solid Tumor

Inclusion Criteria

• •1. Must be ≥18 years of age at the time of signing the informed consent form.
• •2. Must have locally advanced or metastatic solid tumors that have recurred or progressed following treatment with at least 1 prior systemic therapy, or that have not responded to prior systemic therapy; or the patient is unfit for any intensive chemotherapy in the first line setting.
• •3. Must have histologically confirmed IDH1 mutation from testing of a primary or metastatic tumor before first study treatment. Patients must have archival primary tumor biopsy or surgical specimens, or biopsies of recurrence of metastasis for IDH1 mutation confirmation and status of other concurrent gene mutations. Patients shall provide formalin-fixed paraffin-embedded (FFPE) tissue slides without staining, which are shipped to the designated laboratory. The IDH1 mutation must be determined by a validated assay as performed in Clinical Laboratory Improvement Amendments (CLIA)-certified/College of American Pathologists (CAP)-accredited or locally equivalent clinical laboratories. Patients whose tumors have not been tested for IDH1 mutation, must be consented with the pre-screening ICF to allow collection of tumor tissue and testing at the designated qualified central laboratory. These patients may only be consented to the study with the full ICF if they have a documented IDH1 mutation.
• •4. Must have a measurable lesion(s) as per the RECIST v1.1 criteria.
• •5. Patients with chronic HCV infection are acceptable to enroll, if ≥ 4 weeks between achieving sustained viral response and start of study drug. Anti-viral therapy is allowed during the study treatment period.
• •6. Patients with chronic HBV infection may enroll in the study, if HBV DNA is \<1000 copies/mL prior to the start of study treatment. Anti-viral therapy is allowed during the study treatment period.
• •7. Must have life expectancy ≥ 3 months.
• •8. Must have Eastern Cooperative Oncology Group (ECOG) performance status (PS) score ≤ 1.
• •9. Must have a Child-Pugh class A liver score within 7 days prior to first dose of study treatment.
• •10. Must have adequate organ functions as defined below:
• •Absolute neutrophil count (ANC)≥ 1.5 X 109/L, Hemoglobin≥ 80 g/L Creatinine Clearance\* (Cockcroft-Gault Formula) ≥ 60 mL/min Total Bilirubin≤ 2 x ULN,≤ 3 x ULN, for participants with documented Gilbert's syndrome AST and ALT≤ 5 x ULN, Albumin≥ 30 g/L, INR ≤ 1.5 x ULN unless patient is receiving anti-coagulant therapy, aPTT must be within the therapeutic range of intended use of anticoagulants
• •11. Adequate biliary drainage, with no evidence of ongoing infection (patients on maintenance antibiotics are eligible when acute sepsis has resolved)
• •12. Recovery to Grade 1 from any toxicities due to prior therapies, except conditions such as peripheral neuropathy, alopecia and irreversible changes associated with radiation therapy; peripheral neuropathy due to prior therapies must have recovered to ≤ Grade 2.
• •13. Female patients who engage in heterosexual intercourse must be of nonchildbearing potential, defined as either surgically sterile (i.e., hysterectomy, bilateral salpingectomy, or bilateral oophorectomy), OR be postmenopausal with at least 1 year of amenorrhea, OR must agree to use a highly effective method of contraception from the beginning of Screening until at least 90 days after the last dose of study drug.
• •• Acceptable highly effective methods of contraception include:
• •* Combined estrogen-progestin oral hormonal contraception associated with consistent inhibition of ovulation.
• •* Desogestrel based progestin only contraception associated with consistent inhibition of ovulation; this includes oral, injectable, and implantable methods
• •* Intravaginal and transdermal hormone delivery methods
• •* Intrauterine device (with or without hormone elution)
• •* Bilateral tubal occlusion or ligation (must be documented)
• •* Vasectomized partner (must be documented) or
• •* Sexual abstinence (only when it is the usual and preferred lifestyle of the patient)
• •14. Male patients must agree to use a condom when sexually active with a female partner of childbearing potential from Screening until at least 90 days after the last dose of study drug (or be surgically sterile \[i.e., vasectomy with documentation\]; or remain abstinent \[when this is in line with the preferred and usual lifestyle\]. Male patients should also agree not to donate sperm for the duration of the study and until at least 90 days after the last dose of study drug.
• •15. Must be capable of giving signed informed consent as described in Appendix 1 which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
• •16. Must be able to undergo the protocol-specified procedures, including blood tests, urinalysis.