TIBSOVO (ivosidenib tablets) is the only therapy that was studied in a phase 3 trial specifically designed for newly diagnosed patients with mIDH1 AML1,2
TIBSOVO + azacitidine was studied in a global, phase 3, multicenter, randomized, double-blind, placebo-controlled trial.AGILE study design
TIBSOVO + azacitidine was studied in an IC-ineligible patient population reflective of that seen in clinical practice.1See baseline characteristics
TIBSOVO + azacitidine is proven to significantly increase overall survival (OS)
More than threefold improvement in mOS with TIBSOVO + AZA vs AZA alone1,3
Improvements in OS were seen in patients on TIBSOVO + AZA regardless of baseline status, including de novo status, region, age, baseline ECOG PS score, sex, race, baseline cytogenetic risk status, WHO classification of AML, baseline white blood cell count, and baseline percentage of bone marrow blasts.4
24.0 months mOS with TIBSOVO + azacitidine (95% CI, 11.3-34.1) vs 7.9 months with azacitidine alone (95% CI, 4.1-11.3) 1,2,a
29.3 months mOS with TIBSOVO + azacitidine (95% CI, 13.2-NR) vs 7.9 months with azacitidine alone (95% CI, 4.1-11.3) 3,b
bIn the long-term follow-up analysis from the AGILE study, 148 patients were 1:1 randomized: 73 to TIBSOVO + AZA and 75 to PBO + AZA. The data cutoff date was June 2022 with a median follow-up of 28.6 months for the OS analysis.3
Overall survival benefit with TIBSOVO + azacitidine increased over time compared to azacitidine alone
TIBSOVO + azacitidine demonstrated strong and durable responses
TIBSOVO + azacitidine demonstrated significantly higher rates of CR and CR+CRh compared with azacitidine (P<0.0001)1,c
- Median duration of CR was not estimable (NE) as of the data cutoff date in the TIBSOVO + azacitidine arm (95% CI,13.0-NE) and was 11.2 months in the azacitidine arm (95% CI, 3.2-NE)1
- Of the patients who achieved CR or CRh with TIBSOVO + azacitidine2,5:
- 88% remained in remission at 12 months (95% CI, 67.5-96.2)d
- 59% remained in remission at 24 months (95% CI, 17.7-85.1)d
- 38% of patients receiving TIBSOVO + azacitidine achieved CR by Week 24 compared with 11% of patients in the azacitidine arm4
Median time to response with TIBSOVO + azacitidine
- First response (CR, CRi, CRp, PR, or MLFS): 2 months (range, 2-8)5
- CR: 4 months (range, 2-12)1
- CR+CRh: 4 months (range, 2-12)1
cCR was defined as <5% blasts in the bone marrow and no Auer rods, absence of extramedullary disease, full recovery of peripheral blood counts (absolute neutrophil count ≥1000/μL and platelets ≥100,000/μL), and independence of red blood cell transfusions.5 CRh was defined as <5% blasts in the bone marrow and no Auer rods, absence of extramedullary disease, and partial recovery of peripheral blood counts (absolute neutrophil count >500/μL and platelets >50,000/μL).
dPer Kaplan-Meier estimation.
CI, confidence interval; CR, complete remission; CRh, complete remission with partial hematologic recovery; CRi, complete remission with incomplete hematologic recovery; CRp, complete remission with incomplete platelet recovery; MLFS, morphologic leukemia-free state; PR, partial remission.
TIBSOVO + azacitidine resulted in rapid neutrophil recovery and reduction in bone marrow blasts
TIBSOVO + azacitidine demonstrated an increase in absolute neutrophil count recovery by the end of Cycle 14,5
Change in absolute neutrophil count from baseline
BL denotes baseline, defined as the last assessment before start of study treatment; CxDy indicates Cycle x Day y; error bars indicate mean +/- standard error.
Notable decreases in bone marrow blasts were observed from baseline to Week 9 and sustained throughout treatment with TIBSOVO + azacitidine5
Change in bone marrow blasts from baseline
BL denotes baseline, defined as the last assessment before start of study treatment; error bars indicate mean +/- standard error.
- Participants in the trial were to follow a study center visit schedule that included a bone marrow aspirate/biopsy and peripheral blood sampling to evaluate IDH1-mutated cells and to assess disease status and response5
AZA, azacitidine; IDH1, isocitrate dehydrogenase‑1.
Significant improvements in event-free survival (EFS)1,e
Treatment with TIBSOVO + azacitidine resulted in significant improvements in EFS compared with azacitidine1
|Endpoint||TIBSOVO + azacitidine
|Placebo + azacitidine
|EFS, events (%)||47 (65)||62 (84)|
|Treatment failure||43 (60)||59 (80)|
|Relapse||3 (4)||2 (3)|
|Death||1 (1)||1 (1)|
|Hazard ratiof (95% CI)||0.35 (0.17-0.72)|
gTwo sided P value boundary for EFS is 0.0095 and was calculated from the log-rank test stratified by the randomization stratification factors (type of AML and geographic region).
TIBSOVO + azacitidine demonstrated higher EFS rates compared to azacitidine alone5
AML, acute myeloid leukemia; CI, confidence interval, CR, complete remission.
More than half of patients achieved transfusion independence with TIBSOVO + azacitidine
Transfusion independence among patients who were transfusion dependent at baseline3,h,i
Postbaseline RBC and platelet transfusion independence regardless of baseline transfusion status4
hPostbaseline transfusion independence is defined as a period of ≥56 days with no transfusion after the start of study treatment and on or before the end of study treatment + 28 days, disease progression, confirmed relapse, death, or data cutoff date, whichever was earlier.3
iThe 95% confidence interval in the transfusion independence analysis was 37.2-69.9 for the TIBSOVO + azacitidine arm and 7.2-32.1 for the placebo + azacitidine arm.3
RBC, red blood cell.
References: 1. Tibsovo. Package insert. Servier Pharmaceuticals LLC; 2022 2. Montesinos P, Recher C, Vives S, et al. Ivosidenib and azacitidine in IDH1-mutated acute myeloid leukemia. N Engl J Med. 2022;386(16):1519-1531. doi:10.1056/NEJMoa2117344 3. de Botton S, Montesinos P, Vives Polo S, et al. Updated efficacy and safety data from the AGILE study in patients with newly-diagnosed acute myeloid leukemia treated with ivosidenib + azacitidine compared to placebo + azacitidine. Poster presented at: 2023 American Society of Clinical Oncology Annual Meeting; June 2-6, 2023; Chicago, IL. 4. Montesinos P, Recher C, Vives S, et al. Ivosidenib and azacitidine in IDH1-mutated acute myeloid leukemia: supplementary appendix. N Engl J Med. 2022;386(16):1519-1531. doi:10.1056/NEJMoa2117344 5. Data on file. Servier Pharmaceuticals LLC.