Brief Summary
The objective of this study is to investigate the safety, tolerability and preliminary activity of ivosidenib in combination with durvalumab and gemcitabine/cisplatin as first-line therapy in participants with locally advancedat a late stage, far along, unresectable or metastatic cholangiocarcinoma with an IDH1 mutation. The study will begin with a safety lead-in phase (Phase 1b study) to determine the recommended combination dosethe amount of medication taken (RDC) and then will transition to an expansion phase (Phase 2 study) to assess the clinical activity of ivosidenib in combination with durvalumab and gemcitabine/cisplatin at the RCD. During the treatment period participants will have study visits on days 1, 8, and 15 of Cycle 1, on days 1 and 8 of Cycle 2 to 8, and on day 1 of each additional cycle. Cycles 1 through 8 are 21 day cycles, and each following cycle is 28 days. Approximately 30 days and 90 days after treatment has ended, safety follow-up visits will occur and then participants will be followed for survival every 3 months. Study visits may include blood teststesting done to measure the levels of certain substances in the blood, ECG, vital signs, and a physical examinationan examination of your current symptoms, affected area(s) and overall medical history.
Intervention / Treatment
- Drug: Ivosidenib
- Drug: Durvalumab (for the first 8, 21-day, cycles)
- Drug: Gemcitabine (for the first 8, 21-day, cycles)
- Drug: Cisplatin (for the first 8, 21-day, cycles)
- Drug: Durvalumab (starting from cycle 9)
- Drug: Ivosidenib Recommended Combination Dose (RCD)
Inclusion Criteria:
- Have a histopathological confirmed diagnosisthe process of identifying a disease based on signs and symptoms, patient history and medical test results consistent with locally advanced unresectable or metastatic cholangiocarcinoma.
- Have documented IDH1 gene-mutated cholangiocarcinoma based on local or central laboratory testing (R132C/L/G/H/S mutation variants tested).
- Have at least one evaluable and measurable lesion as defined by RECIST v1.1.
- Have adequate bone marrowsoft, spongy tissue found in bones that makes blood cells function as evidenced by:
- Absolute neutrophil count ≥ 1,500/mm3 or 1.5 ×109/L
- Hemoglobin ≥ 9 g/dL
- Platelet count ≥ 100,000/mm3 or 100 × 109/L
- Have adequate hepatic function as evidenced by:
- Serum bilirubin ≤ 2.0 × the upper limit of normal (ULN); this will not apply to patients with confirmed Gilbert’s syndrome. Any clinically significant biliary obstruction should be resolved before randomization
- Aspartate aminotransferase (AST), and alanine aminotransferase (ALT) ≤ 2.5 × ULN; for patients with hepatic metastases, ALT and AST ≤ 5.0 × ULN
- Have adequate renal function, defined as: creatinine clearance > 60 mL/min per 24 hour urine or as calculated on the Cockcroft-Gault formula (using actual body weight):
Creatine CL (mL/min)= (140 – Age) × (weight in kg) × (0.85 if female)/72 × serum creatinine (mg/dL)