AGILE: trial | Bending the Curve: Trial by Trial

AGILE

Ivosidenib and azacitidine in IDH1-mutated acute myeloid leukemia

Population

Newly diagnosed IDH1-mutated AML in patients ineligible for intensive induction chemotherapy

Design

Randomized, placebo-controlled phase 3 trial. Oral ivosidenib 500 mg once daily or matched placebo with azacitidine 75 mg/m2 for 7 days in 28-day cycles. Primary end point: event-free survival, defined as time from randomization until treatment failure (no complete remission by week 24), relapse from remission, or death.

Primary endpoint

EFS

Arms

Ivosidenib + azacitidine (experimental, n = 72): Ivosidenib 500 mg daily plus azacitidine 75 mg/m2 for 7 days in 28-day cycles
Placebo + azacitidine (control, n = 74): Matched placebo plus azacitidine 75 mg/m2 for 7 days in 28-day cycles

People

Montesinos P

EFSHR 0.33 (95% CI 0.16–0.69)Δ 12-month EFS+25 pointsOSHR 0.44 (95% CI 0.27–0.73)Δ median OS+16.1 months

Show the numbers

Results reported for AGILE
Endpoint	Analysis	Ivosidenib + azacitidine	Placebo + azacitidine	Effect
EFS	primarymedian follow-up 12.4 monthsMontesinos 2022	37% at 12 mo	12% at 12 mo	HR 0.33 (95% CI 0.16–0.69)P=0.002Hazard ratio for treatment failure, relapse from remission, or death. The abstract gives no median EFS.
OS	primaryMontesinos 2022	median 24 months	median 7.9 months	HR 0.44 (95% CI 0.27–0.73)P=0.001The abstract states the median follow-up of 12.4 months for the event-free survival analysis, not for overall survival, so none is recorded here. The abstract lists overall survival after event-free survival; whether it was a key secondary end point is not stated there.

Results reported for AGILE
Endpoint	Analysis	Ivosidenib + azacitidine	Placebo + azacitidine	Effect
EFS	primarymedian follow-up 12.4 monthsMontesinos 2022	37% at 12 mo	12% at 12 mo	HR 0.33 (95% CI 0.16–0.69)P=0.002Hazard ratio for treatment failure, relapse from remission, or death. The abstract gives no median EFS.
OS	primaryMontesinos 2022	median 24 months	median 7.9 months	HR 0.44 (95% CI 0.27–0.73)P=0.001The abstract states the median follow-up of 12.4 months for the event-free survival analysis, not for overall survival, so none is recorded here. The abstract lists overall survival after event-free survival; whether it was a key secondary end point is not stated there.

Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.

Data table

Endpoint	HR	95% CI
EFS	0.33	0.16–0.69
OS	0.44	0.27–0.73

Illustrative — modelled from reported values, not trial data. OS, primary.

Show curves

Ivosidenib + azacitidine (experimental)
Placebo + azacitidine (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)

Months	Ivosidenib + azacitidine	Placebo + azacitidine
0	100.0%	100.0%
15	64.8%	26.8%
30	42.0%	7.2%
45	27.3%	1.9%
60	17.7%	0.5%

Appears in

2017 IDH1 and IDH2 inhibitors in AML: enasidenib, ivosidenib, olutasidenib

Sources

Montesinos P, Recher C, Vives S, Zarzycka E, Wang J, Bertani G, et al. Ivosidenib and Azacitidine in IDH1-Mutated Acute Myeloid Leukemia. N Engl J Med. 2022;386(16):1519-1531.
PubMed DOI