IDH1 mutant cholangiocarcinoma and other solid tumors
Conditions
Interventions
AB-218:Medication
Sponsors
Peking Union Medical College Hospital, Chinese Academy of Medical Sciences
Eligibility
Sex/Gender
All
Inclusion criteria
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 (See Appendix 8) within 7 days prior to first dose of study treatment. 10. Must have adequate organ functions as defined below: Hematology(Absoluteneutrophil count (ANC) = 1.5 X 109/L, Hemoglobin = 80 g/L ), Renal (Creatinine Clearance* (Cockcroft-Gault Formula)= 60 mL/min Hepatic (Total Bilirubin = 2 x ULN ,= 3 x ULN, for participants with documented Gilberts syndrome ,AST and ALT= 5 x ULN ,Albumin= 30 g/L Note: No albumin supplement or human plasma infusion is allowed within the last 14 days prior to the 1st study dose. Coagulation (INR aPTT = 1.5 x ULN unless patient is receiving anti-coagulant therapy, aPTT must be within the therapeutic range of intended use of anticoagulants. Note: An out of range laboratory test will be repeated up to 2 times before declaring a screen failure, and after expiration of screening window, patients will be re-screened. * Creatinine clearance formula is referred to Appendix 2. 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 14: 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 surg
Exclusion criteria
Exclusion criteria: 1. Patients diagnosed with IDH1 mutant glioma or acute myeloid leukemia (AML). 2. Patients with history or complication of any of the following diseases within 3 months prior to the initial dose of the investigational drug. ? Myocardial infarction ? Severe or unstable angina pectoris ? Coronary or peripheral endovascular treatment ? Heart failure ? Cerebrovascular disorder including transient ischemic attack, stroke, central nervous system (CNS) bleeding. 3. Uncontrolled active systemic fungal, bacterial, or other infection (despite appropriate antibiotics or other treatment). 4. HIV infection as determined by an HIV antibody test. 5. Presence of Grade 3 ascites, as defined in the Guidance on the Management of Ascites and Complications in Cirrhosis 36. The patient has significant bloating, tests positive for shifting dullness, and may have abdominal distension leading to umbilical hernia on assessment with ultrasound, the ascites occupies the entire abdominal cavity, and the middle abdomen is filled with ascites, with a depth of >10 cm. 6. Gastrointestinal diseases that may interfere with oral ingestion of the study drug or may affect absorption of the study drug. 7. Prior anticancer therapy, within the applicable periods shown below, before the start of the protocol treatment: ? Systematic Therapy: within 3 weeks ? Radical Surgery: within 3 weeks ? Radiation therapy: within 12 weeks (excluding the palliative radiotherapy or radiotherapy on the non-target lesions) ? Infusion of blood component or the recombinant human blood product, for example, RBC, Platelet, rhGSF: within 2 weeks 8. Have received prior anti-cancer therapy targeted to the IDH1 mutation. 9. Patients taking substrates of cytochrome CYP2C8, CYP2C9, and CYP3A4 with narrow therapeutic window, should be excluded unless they can be transferred to other medications prior to enrolling. Patients taking sensitive CYP 2C8, 2C9 or 3A4 substrate medications may require dosage adjustment unless they can be transferred to other medications within = 5 half-lives prior to dosing. A list of prohibited and sensitive cytochrome substrates is in Appendix 7. 10. Patients taking sensitive substrates of P-gp and BCRP transporters should be excluded unless they can be transferred to other medications prior to enrolling. Patients taking sensitive substrates of P-gp and BCRP may require dosage adjustment unless they can be transferred to other medications within = 5 half-lives prior to dosing. A list of sensitive substrates of P-gp and BCRP transporters is in Appendix 7. 11. Known hypersensitivity to the investigational medicinal product or to any drug with similar chemical structure or to any other excipient present in the pharmaceutical form of the investigational medicinal product(s) 12. Advanced arrhythmia of Grade = 2 per Common Terminology Criteria for Adverse Events (CTCAE) v5.0, uncontrolled atrial fibrillation (any grade) and QTcF >470 msec for females or >450 msec for males 13. Pregnant or breastfeeding female patient. 14. Psychiatric disease or symptoms that may interfere with continuous participation in the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Treatment-Emergent Adverse Events (TEAEs);Dose limiting toxicity (DLT) incidence; | — |
Secondary
| Measure | Time frame |
|---|---|
| Overall Response Rate;Duration of Response;Disease Control Rate;Progress Free Survival;Overall Survival; | — |
Countries
China
Contacts
Public ContactZhao Haitao
Peking Union Medical College Hospital, Chinese Academy of Medical Sciences
Outcome results
None listed