A Phase IV, Prospective, Open Label, Multi-Centre Study of Ivosidenib Based Therapy in Indian Participants with Isocitrate Dehydrogenase 1 Mutation (mIDH1) positive, previously treated Locally Advanced or Metastatic Cholangiocarcinoma (LA/mCCA) or standard induction chemotherapy ineligible Newly Diagnosed Acute Myeloid Leukaemia (AML).

Ivosidenib is a first-in-class inhibitor of mutated IDH1 indicated for treatment of patients with previously treated Locally Advanced or Metastatic Cholangiocarcinoma (LA/mCCA), and newly diagnosed Acute Myeloid Leukaemia (AML) who are not eligible to receive standard induction chemotherapy.

 In the CCA cohort, eligible participants must have a confirmed diagnosis of CCA with an IDH1 R132 mutation and must not be eligible for curative-intent surgery, transplantation, or ablative therapies. Screening procedures will be conducted within 28 days prior to treatment initiation and will include medical history, physical examination, ECG and laboratory assessments. Participants must have received at least one prior line of systemic therapy. Upon enrolment, participants will begin treatment with oral ivosidenib 500 mg once daily, starting on Cycle 1 Day 1 (C1D1). Each treatment cycle will last 28 days, with continuous daily dosing throughout the cycle. Monthly study visits will occur on Day 1 of each cycle. Participants will be treated for six cycles, unless discontinued earlier due to relapse, disease progression, TEAEs resulting in discontinuation, confirmed pregnancy, or withdrawal of consent. A window period of ±3 days will be allowed for visits up to Cycle 2 Day 1. From Cycle 2 Day 15 onwards, a window period of ±5 days will be allowed. The End of Study (EOS) visit will be conducted within 1 week from the last study treatment dose. In the AML cohort, newly diagnosed participants with confirmed IDH1 R132-mutated AML who are ineligible for standard induction chemotherapy will be enrolled. Screening procedures will be conducted within 28 days prior to treatment initiation and will include medical history, physical examination, ECG and laboratory assessments. Participants will receive daily oral Ivosidenib throughout each 28-day treatment cycle, in combination with azacitidine at 75 mg/m²/day, administered intravenously during the first seven days of each cycle. All participants will be treated for six cycles, unless discontinued earlier due to relapse, disease progression, TEAEs resulting in discontinuation, confirmed pregnancy, or withdrawal of consent. A window period of ±3 days will be allowed for visits up to Cycle 2 Day 1. From Cycle 2 Day 15 onwards, a window period of ±5 days will be allowed. The End of Study (EOS) visit will be conducted within 1 week from the last study treatment dose.

 Safety assessments will be conducted at each visit and will include ECGs, vital signs, physical examinations and laboratory tests. AE monitoring will be done throughout the study, especially the Adverse Event of Special Interest (AESI) of QTc interval prolongation will be noted. Tumor assessments to evaluate the disease or the response to treatment will be performed according to local standards (CT/MRI/FDG PET-CT of chest, abdomen and pelvis) at screening, C3D15 and at the EOS visit.Safety and effectiveness will be monitored throughout the study, with particular attention to AESIs such as QTc interval prolongation and differentiation syndrome. Disease response will be evaluated as per the modified IWG response criteria ELN 2022 guidelines, at screening, C2D1, C4D2 and at the EOS visit. Participants achieving stable disease will not be considered treatment failures unless they fail to respond after six months of therapy.

 In 2025, ivosidenib was approved by the Health Authority in India for the same indications. This study is being conducted as part of the regulatory requirement mandating the conduct of a phase 4 interventional clinical trial in these indications.