Evaluating ivosidenib for the treatment of acute myeloid leukemia

Figures & data

Figure 1. Enzymatic activities of wild type and mutated IDH enzymes

Table 1. Clinical trials evaluating ivosidenib in AML

Trial	Patient population	Results	Safety	Reference
NCT02074839 phase I ivosidenib monotherapy	R/R IDH1-mutated AML n = 268	CR/CRh: 30.4% (median time to CR/CRh 2.7 months, median duration of response 6.5 months) CR 21.6% (median time to CR 2.8 months, median duration of response 9.3 months) ORR 41.6% (median time to first response 1.9 months, median duration of response 6.5 months) transfusion-independence: 35% (for >56 days)	treatment-related grade ≥3 AEs: 21% prolonged QT interval, IDH-DS, leukocytosis	[44]
NCT02677922 phase Ib ivosidenib + azacitidine	Newly diagnosed IDH1-mutated AML n = 23	ORR 78% (median time to response 1.8 months, median duration of response NR) CR 61% (median time to CR 3.7 months, median duration of response NR)	AEs consistent with monotherapy ivosidenib or azacitidine Most common grade 1 and 2 GI events	[50,51]
NCT02632708 phase I ivosidenib + induction therapy	Newly diagnosed IDH1-mutated AML N = 47	CR/CRi/CRp: 93% (de novo AML), 46% (sAML)	AEs grade ≥3 IDH-DS: 6% QT interval prolongation: 2%	[52]
NCT03013998 phase II ivosidenib + azacitidine	Newly diagnosed IDH1-mutated AML, not eligible for standard induction chemotherapy	Ongoing
NCT03471260 phase Ib/II ivosidenib + venetoclax ± azacitidine	IDH1-mutated AML R/R or newly diagnosed not eligible for standard induction chemotherapy	Ongoing
NCT04044209 phase II ivosidenib + nivolumab	R/R IDH1-mutated AML	Ongoing
NCT03564821 phase I ivosidenib maintenance therapy after allo-SCT	IDH1-mutated malignancies	Ongoing
NCT03173248 AGILE study phase III azacitidine + ivosidenib/placebo	IDH1-mutated AML newly diagnosed not eligible for standard induction chemotherapy n = 392	Ongoing
NCT03839771 HOVON/AML-SG AML study intensive chemotherapy + ivosidenib/placebo (IDH1m) or enasidenib/placebo (IDH2m) + maintenance therapy for up to 2 years	IDH1-mutated AML newly diagnosed eligible for intensive chemotherapy n = 484	Ongoing

Table

Drug name	Ivosidenib
Phase	Launched
Indication	AML
Pharmacology description	Isocitrate dehydrogenase 1 inhibitor
Route of administration	Oral
Chemical structure
Pivotal trial(s)	[44]

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