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.
TIBSOVO + azacitidine was studied in an IC-ineligible patient population reflective of that seen in clinical practice.1
AML, acute myeloid leukemia; IC, induction chemotherapy; mIHD1, mutant isocitrate dehydrogenase-1.
Threefold improvement in overall survival (OS) with TIBSOVO + azacitidine1
TIBSOVO + azacitidine delivered a median OS of 24.0 months vs 7.9 months with azacitidine.

Endpoint | TIBSOVO + azacitidine (n=72)1 |
Placebo + azacitidine (n=74)1 |
|
---|---|---|---|
OS, events (%) | 28 (39) | 46 (62) | |
Median OS, months (95% CI) | 24.0 (11.3-34.1) | 7.9 (4.1-11.3) | |
Hazard ratioa (95% CI) | 0.44 (0.27-0.73) | ||
P valueb | 0.0010 |
Endpoint | TIBSOVO + azacitidine (n=72)1 |
||
---|---|---|---|
OS, events (%) | 28 (39) | ||
Median OS, months (95% CI) | 24.0 (11.3-34.1) | ||
Hazard ratioa (95% CI) | 0.44 (0.27-0.73) | ||
P valueb | 0.0010 |
Endpoint | Placebo + azacitidine (n=74)1 |
||
---|---|---|---|
OS, events (%) | 46 (62) | ||
Median OS, months (95% CI) | 7.9 (4.1-11.3) | ||
Hazard ratioa (95% CI) | 0.44 (0.27-0.73) | ||
P valueb | 0.0010 |
The two-sided P value boundary for OS is 0.0034.
a Hazard ratio was estimated using a Cox proportional hazards model stratified by the randomization stratification factors (type of AML and geographic region) with placebo + azacitidine as the denominator.
bTwo-sided P value was calculated from the log-rank test stratified by the randomization stratification factors (type of AML and geographic region).
Overall survival benefit was consistent across subgroups, 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.3
AML, acute myeloid leukemia; AZA, azacitidine; CI, confidence interval; ECOG PS, Eastern Cooperative Oncology Group Performance Status; HR, hazard ratio; WHO, World Health Organization.
Significant improvements in event-free survival (EFS)1
Treatment with TIBSOVO + azacitidine resulted in significant improvements in EFS compared with azacitidine1 | |||
---|---|---|---|
Endpoint | TIBSOVO + azacitidine (n=72) |
Placebo + azacitidine (n=74) |
|
EFS, events (%) | 47 (65) | 62 (84) | |
Treatment failure | 43 (60) | 59 (80) | |
Relapse | 3 (4) | 2 (3) | |
Death | 1 (1) | 1 (1) | |
Hazard ratioc (95% CI) | 0.35 (0.17-0.72) | ||
P valued | 0.0038 |
Treatment with TIBSOVO + azacitidine resulted in significant improvements in EFS compared with azacitidine1 | |||
---|---|---|---|
Endpoint | TIBSOVO + azacitidine (n=72) |
||
EFS, events (%) | 47 (65) | ||
Treatment failure | 43 (60) | ||
Relapse | 3 (4) | ||
Death | 1 (1) | ||
Hazard ratioc (95% CI) | 0.35 (0.17-0.72) | ||
P valued | 0.0038 |
Treatment with TIBSOVO + azacitidine resulted in significant improvements in EFS compared with azacitidine1 | |||
---|---|---|---|
Endpoint | Placebo + azacitidine (n=74) |
||
EFS, events (%) | 62 (84) | ||
Treatment failure | 59 (80) | ||
Relapse | 2 (3) | ||
Death | 1 (1) | ||
Hazard ratioc (95% CI) | 0.35 (0.17-0.72) | ||
P valued | 0.0038 |
The two-sided P value boundary for EFS is 0.0095.
cHazard ratio was estimated using a Cox proportional hazards model stratified by the randomization stratification factors (type of AML and gegeographic region) with placebo + azacitidine as the denominator.
dTwo sided P value was calculated from the 1-sided log-rank test stratified by the randomization stratification factors (type of AML and geographic region).
- 12-month EFS rate: 37.4% with TIBSOVO + azacitidine (95% CI, 25.9-48.9) vs 12.2% with azacitidine (95% CI, 4.3-24.4)4
- 18-month EFS rate: 33.3% with TIBSOVO + azacitidine (95% CI, 20.9-46.2) vs 6.1% with azacitidine (95% CI, 0.7-20.9)4
AML, acute myeloid leukemia; CI, confidence interval; EFS, event-free survival, defined as time from randomization until treatment failure (ie, failure to achieve complete remission by Week 24), relapse from remission, or death from any cause, whichever occurred first.
TIBSOVO + azacitidine demonstrated significantly higher rates of complete remission (CR) and CR+CRh compared with azacitidine (P<0.0001)1

- Median duration of complete response 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)4
- Of the patients who achieved CR or CRh with TIBSOVO + azacitidine4:
- 80.5% remained in remission at 12 months (95% CI, 54.4-92.5)e
- 53.6% remained in remission at 24 months (95% CI, 17.0-80.3)e
- 37.5% of patients receiving TIBSOVO + azacitidine achieved CR by Week 24 compared with 10.8% of patients in the azacitidine arm3
Median time to response with TIBSOVO + azacitidine
- First response (CR, CRi, CRp, PR, or MLFS): 2 months (range, 2-8)4
- CR: 4 months (range, 2-12)1
- CR+CRh: 4 months (range, 2-12)1
ePer Kaplan-Meier estimation.
CI, confidence interval; CR, complete remission, 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 transfusions4; CRh, complete remission with partial hematological recovery, 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)4; CRi, complete remission with incomplete hematologic recovery; CRp, complete remission with incomplete platelet recovery; MLFS, morphologic leukemia-free state; PR, partial remission.
Nearly 50% conversion to transfusion independence2,3
Among patients who were transfusion dependent at baseline, a higher percentage of patients converted to transfusion independence with TIBSOVO + azacitidine than with azacitidine

Regardless of baseline transfusion status, more patients experienced postbaseline red blood cell and platelet transfusion independence with TIBSOVO + azacitidine than with azacitidine3

Postbaseline 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.4
TIBSOVO + azacitidine enabled improvements in key hematologic parameters3
TIBSOVO + azacitidine resulted in rapid neutrophil recovery3
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.
TIBSOVO + azacitidine resulted in decreased bone marrow blasts4
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 response4
AZA, azacitidine; IDH1, isocitrate dehydrogenase-1.