A Phase 1b/2, Safety Lead-in and Dose-Expansion, Open Label, Multicenter Trial Investigating 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

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 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.

Eligibility

Age range

18+ years

Sex

All

Healthy volunteers

No

Interventions

• Drug
  Ivosidenib

  Two 250 mg tablets, totaling 500 mg, administered orally once daily, taken continuously throughout treatment duration

• Drug
  Durvalumab (for the first 8, 21-day, cycles)

  1500mg intravenous (IV) infusion every 3 weeks, for a maximum of 8 (21-day) cycles

• Drug
  Gemcitabine (for the first 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

• Drug
  Cisplatin (for the first 8, 21-day, cycles)

  25 mg/m\^2 IV infusion on days 1 and 8 of every 21-day cycle, for a maximum of 8 cycles

• Drug
  Durvalumab (starting from cycle 9)

  1500mg intravenous (IV) infusion every 4 weeks, starting from cycle 9. Cycles are 28 days long, starting Cycle 9.

• Drug
  Ivosidenib Recommended Combination Dose (RCD)

Locations (37)