Institut de Recherches Internationales Servier
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 advanced, 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 dose (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 tests, ECG, vital signs, and a physical examination.
Inclusion Criteria: * Have a histopathological confirmed diagnosis 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 marrow 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: * Ser…
Two 250 mg tablets, totaling 500 mg, administered orally once daily, taken continuously throughout treatment duration
1500mg intravenous (IV) infusion every 3 weeks, for a maximum of 8 (21-day) cycles
1000 mg/m2 IV infusion on days 1 and 8 of every 21-day cycle, for a maximum of 8 cycles
25 mg/m\^2 IV infusion on days 1 and 8 of every 21-day cycle, for a maximum of 8 cycles
1500mg intravenous (IV) infusion every 4 weeks, starting from cycle 9. Cycles are 28 days long, starting Cycle 9.
RCD administered orally once daily, taken continuously throughout treatment duration