Servier Canada
TIBSOVO®
PrTIBSOVO® (ivosidenib)

The AGILE study: Overview

Study design1,2

Global, double-blind, randomized, placebo-controlled, phase 3 trial in patients with a confirmed diagnosis of previously untreated AML with an IDH1 mutation

146 patients with AML and confirmed IDH1 mutation who were ineligible for intensive induction chemotherapy

ECOG PS 0 to 2

Untreated with IDH1 inhibitors or hypomethylating agents for myelodysplastic syndrome

1:1 randomization (n=146)*#

TIBSOVO® 500 mg QD orally + AZA 75 mg/m2/day SC or IV (n=72)

Placebo QD orally + AZA 75 mg/m2/day SC or IV (n=74)

TIBSOVO® or matched PBO was administered in combination with AZA for 1 week every 4 weeks until the end of the study, disease progression or unacceptable toxicity.

Primary endpoint
Event-free survival

Secondary endpoints

  • Overall survival
  • Complete remission
  • Complete remission or complete remission with partial hematologic recovery
  • Objective response
  • Safety profile

*Patients were stratified by geographic region (US, Canada, Western Europe, Israel & Australia, Japan, and ROW) disease status (primary vs secondary AML). Crossover to TIBSOVO® + AZA was permitted for eligible patients in the PBO + AZA arm if the benefit–risk profile was determined to favour the TIBSOVO® + AZA arm.
#Number of randomized patients at data cut off: 146 patients (TIBSOVO® arm, n=72; PBO arm, n=74).

Adapted from the TIBSOVO® Product Monograph and Montesinos et al. 2022.

Key eligibility criteria

  • ≥18 years of age
  • Confirmed diagnosis of previously untreated AML with mIDH1 as determined with the FDA-approved Abbott RealTime IDH1 in vitro PCR assay
  • Untreated with IDH1 inhibitors or hypomethylating agents for myelodysplastic syndrome
  • ECOG PS 0-2
  • Adequate liver and kidney function
  • Meeting ineligibility criteria for intensive induction chemotherapy, defined by an age of ≥75 years or at least 1 of the following medical conditions:
    • ECOG PS of 2
    • A severe cardiac disorder (e.g., congestive heart failure resulting in treatment, a left ventricular EF ≤50%, or chronic stable angina)
    • A severe pulmonary disorder (e.g., a DLCO ≤65% or an FEV1 of ≤65%)
    • A creatinine clearance <45 mL per minute
    • A bilirubin level >1.5 times the upper limit of the normal range

Study population demographics

Demographic and clinical characteristics at baseline were similar between the two arms

TIBSOVO® + azacitidine 
(N=72)

Age (Years) Median (Min, Max)

76 (58, 84)

Age Categories, n (%)

< 65 years

4 (6)

65 years to < 75 years

29 (40)

≥ 75 years

39 (54)

Sex, n (%)

Male

42 (58)

Female

30 (42)

Race, n (%)

Asian

15 (21)

White

12 (17)

Black or African American

0

Other

1 (1)

Not provided

44 (61)

Disease Characteristics

ECOG PS, n (%)

0

14 (19)

1

32 (44)

2

26 (36)

IDH1 Mutation, n (%)1

R132C

45 (63)

R132H

14 (19)

R132G

6 (8)

R132L

3 (4)

R132S

2 (3)

Wild type

1 (1)

Missing

1 (1)

Cytogenetic Risk Status2  n (%)

Favorable

3 (4)

Intermediate

48 (67)

Poor

16 (22)

Other

3 (4)

Missing

2 (3)

Transfusion Dependent at Baseline3 
n (%)

39 (54)

Type of AML, n (%)

De novo AML

54 (75)

Secondary AML

18 (25)

Therapy-related AML

2 (3)

MDS related

10 (14)

MPN related

4 (6)

ECOG PS: Eastern Cooperative Oncology Group Performance Status; MPN: myeloproliferative neoplasm; MDS: myelodysplastic syndrome.
1Using confirmatory Abbott RealTime IDH1 assay testing results.
2Cytogenetic risk status: National Comprehensive Cancer Network (NCCN) guidelines.
3Patients were defined as transfusion dependent at baseline if they received any red blood cell or platelet transfusion within 56 days prior to the first dose of TIBSOVO®.

Adapted from the TIBSOVO® Product Monograph.

Consult the TIBSOVO® Product Monograph

2-HG: 2-hydroxyglutarate; α-KG: alpha-ketoglutarate; AML: acute myeloid leukemia; AZA: azacitidine; PBO: placebo; CCA: cholangiocarcinoma; CI: confidence interval; CR: complete response; CRh: complete response with partial hematologic recovery; CTCAE: Common Terminology Criteria for Adverse Events; DLCO: diffusing capacity for carbon monoxide; ECG: electrocardiogram; ECOG PS: Eastern Cooperative Oncology Group Performance Status; EFS: event-free survival; eGFR: estimated glomerular filtration rate; FEV1: forced expiratory volume in 1 second; HR: hazard ratio; IDH1: isocitrate dehydrogenase-1; IRC: Independent Radiology Centre; IV: intravenous; mIDH1: mutated isocitrate dehydrogenase-1; MOA: mechanism of action; NCCN: National Comprehensive Cancer Network; OR: odds ratio; OS: overall survival; PBO: placebo; PCR: polymerase chain reaction; PD: pharmacodynamics; PK: pharmacokinetics; QD: daily; RECIST: Response Evaluation Criteria In Solid Tumors; SC: subcutaneous.

References:

  1. TIBSOVO® Product Monograph. Servier Canada. July 19, 2024.
  2. Montesinos P, et al. N Engl J Med. 2022 Apr 21;386(16):1519–1531.
  3. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Acute Myeloid Leukemia Version 2.2025 — January 27, 2025.
  4. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Biliary Duct Cancers Version 6.2024 — January 10, 2025.
  5. Abou-Alfa GK, et al. Lancet Oncol. 2020 Jun;21(6):796-807.
  6. Zhu AX, et al. JAMA Oncol. 2021 Nov 1;7(11):1669-1677.
  7. Dammacco F, Silvestris F, eds. Oncogenomics: From Basic Research to Precision Medicine. Academic Press; 2019.
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