AUGMENT-101:
Inclusive clinical trial design
As the first pivotal trial of its kind, AUGMENT-101 assessed the efficacy and safety of Revuforj in 241 adult and pediatric patients with R/R
KMT2A-translocated acute leukemia or R/R NPM1m AML1
AUGMENT-101:
an open-label, multicohort, multicenter, phase 1/2 clinical trial1,2
Cohort 2A & 2B:
KMT2A-translocated
AML, ALL, and MPAL
Cohort 2C
NPM1m
AML
A total of 241 patients received Revuforj
• 207 were adults • 34 were pediatric
Administered orally,
twice daily*
Patients ≥40 kg: Dose ≈ 160 mg
Patients <40 kg: Dose based on BSA
Treated until disease progression, unacceptable toxicity, failure to achieve morphological leukemia-free state (MLFS) by 4 cycles of treatment, or hematopoietic stem cell transplantation (HSCT)
Administered twice daily (ie, every 12 hours) in 28-day continuous cycles with a strong CYP3A4 inhibitor.
Primary endpoints1
-
Rate of complete remission (CR) + CR with partial hematological recovery (CRh)
-
Safety and tolerability
Key inclusion criteria1,2
-
At least 30 days of age
-
Relapsed or refractory active acute myeloid leukemia harboring an NPM1 mutation
-
Bone marrow blasts ≥5% or reappearance of blasts in peripheral blood
-
A susceptible NPM1 mutation was confirmed using NGS or PCR of the last exon of NPM1
-
-
White blood cell count below 25,000/μL (25 Gi/L) at time of enrollment
-
ECOG performance status score 0-2 or Karnofsky/Lansky score ≥50
Revuforj was studied in a broad range of difficult-to-treat patients with R/R NPM1m AML1
Patient Demographics (N=65)
Median Age (years) (Range)
65 (11, 84)
Age, n (%)
<17 years old
1 (2)
17 to <65 years old
31 (48)
≥65 years old
33 (51)
Sex, n (%)
Male
26 (40)
Female
39 (60)
Race, n (%)
Black or African American
6 (9)
Asian
4 (6)
White
38 (59)
Multiple
1 (2)
Other
3 (5)
Missing
13 (20)
Ethnicity, n (%)
Hispanic or Latino
5 (8)
Not Hispanic or Latino
50 (77)
Not Reported
9 (14)
Missing
1 (2)
Disease Characteristics (N=65)
NPM1 mutation type
Type A
43 (66)
Type B
4 (6)
Type D
4 (6)
Non-A, B, or D
5 (8)
Not available
9 (14)
Prior treatment
Median number of prior
regimens (min, max)
2 (1, 7)
Prior stem cell
transplantation, n (%)
15 (23)
23% of patients had received at least 1 prior HSCT at baseline1
23% of patients had received at least 1 prior HSCT at baseline1
ALL=acute lymphoblastic leukemia; AML=acute myeloid leukemia; BSA=body surface area; CYP3A4=cytochrome P450 3A4; ECOG=Eastern Cooperative Oncology Group; KMT2A=lysine methyltransferase 2A; MPAL=mixed-phenotype acute leukemia; NGS=next-generation sequencing; NPM1m=mutant nucleophosmin 1; PCR=polymerase chain reaction; R/R=relapsed/refractory.
AUGMENT-101 pivotal trial results: R/R NPM1-mutated AML
Established complete remission with a single-agent, targeted therapy1
23
%
achieved
CR + CRh
(primary endpoint)
(n=15/65)
(95% CI: 13.5, 35.2)
-
The efficacy of Revuforj was evaluated in a difficult-to-treat patient population consisting of 65 patients with relapsed/refractory NPM1m AML
-
At baseline, patients had received a median of 2 previous regimens (range: 1–7), with 23% (15/65) having received at least 1 stem cell transplant
Median time to CR + CRh
2.8
MONTHS
(range: 1.8–9.6 months)
Median duration of CR + CRh
4.5
MONTHS
(95% CI: 1.2, 8.1)
Median follow-up was 3.8 months
(range: 0.1–29.9 months)
Rate of transfusion independence1*
17% (n=8/46) of patients who were transfusion dependent became transfusion independent
68% (n=13/19) of patients remained transfusion independent while on Revuforj
The majority of patients (n=46/65) were dependent on RBC and/or platelet transfusions at baseline. Nineteen patients (n=19/65) were independent of both RBC and platelet transfusions at baseline. Patients were defined as transfusion independent if they became or remained independent of both RBC and platelet transfusions during any 56-day post-baseline period.
Rate of transplant following Revuforj1
11
%
(n=7/65)
of patients
proceeded
to HSCT
NCCN
RECOMMENDED
Targeted
treatment
option
National Comprehensive Cancer Network® (NCCN®)
Revumenib (Revuforj) is an NCCN Category 2A recommended treatment for R/R NPM1m AML, R/R KMT2Ar AML, R/R KMT2Ar Adult ALL, and R/R KMT2Ar Pediatric ALL. This makes it the only menin inhibitor in multiple NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®).3-5
NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
Additional data from a prespecified phase 2 analysis of
AUGMENT-101: R/R NPM1-mutated AML6
The phase 2 analysis consisted of 84 adult and pediatric patients with R/R NPM1m AML
- 84 patients had received at least 1 dose of Revuforj (safety population)
-
The first 64 adult patients in the study who met the efficacy-evaluable criteria were included in the protocol-defined primary efficacy analysis
- The 1 pediatric patient met the criteria but was not included in the primary efficacy analysis
Patients were heavily pretreated and had challenging disease characteristics at baseline6
36% had received 3+ prior therapies
75% had received prior treatment with venetoclax
47% had received prior treatment with an FLT3 inhibitor
Clinical Characteristics (N=64)
Co-occurring mutations, n (%)
FLT3-ITD
22 (34)
FLT3-TKD
4 (6)
RAS
2 (3)
TP53
4 (6)
4.8% of patients (n=4/84) discontinued Revuforj due to treatment-related adverse reactions6
Clinical Characteristics (N=64)
Previous therapies, n (%)
Median (range)
2 (1–7)
≥3
23 (36)
≥4
14 (22)
Venetoclax
48 (75)
HSCT
>1 previous HSCT
14 (22)
4 (6)
FLT3 inhibitor
30 (47)
IDH1 inhibitor
3 (5)
IDH2 inhibitor
4 (6)
4.8% of patients (n=4/84) discontinued Revuforj due to treatment-related adverse reactions6
Phase 2 analysis data:
Complete remission with Revuforj6
23
%
achieved
CR + CRh
(primary endpoint)
(n=15/64)
(95% CI: 13.8, 35.7)
-
Median time to first CR + CRh was 2.8 months (range: 1.8–8.8 months)
-
Median duration of CR + CRh response was 4.7 months (95% CI: 1.2, 8.2)
Nearly half of patients achieved a clinical response6
47
%
overall response rate
(secondary endpoint)
(n=30/64)
(95% CI: 34.3, 59.8)
-
Median time to first response was 1.8 months (range: 0.9–4.6 months)
-
Median duration of first response was 4.4 months (95% CI: 1.2, 5.6)
-
Median time to first response was 1.8 months (range: 0.9–4.6 months)
-
Median duration of first response was 4.4 months (95% CI: 1.2, 5.6)
Observed among patients who achieved an overall response6:
17% (n=5/30) proceeded to HSCT
30
%
composite complete remission rate
(CR + CRh + CRp + CRi)
(secondary endpoint)
(n=19/64)
(95% CI: 18.9, 42.4)
Responses were seen across subgroups regardless of co-mutations, prior HSCT, or number of prior lines of therapy, though the study was not powered to evaluate differences among subgroups6
Secondary endpoints, including overall response rate and composite complete remission rate, were predefined but were not statistically powered to draw any conclusions or make any comparisons.
AML=acute myeloid leukemia; CI=confidence interval; CR=complete remission; CRh=CR with partial hematological recovery; CRi=CR with incomplete blood count recovery; CRp=CR with incomplete platelet recovery; HSCT=hematopoietic stem cell transplantation; NPM1m=mutant nucleophosmin 1; RBC=red blood cell; R/R=relapsed/refractory.
References: 1. Revuforj® [Prescribing Information]. Syndax Pharmaceuticals, Inc.; October 2025. 2. ClinicalTrials.gov identifier: NCT04065399. https:// clinicaltrials.gov/study/NCT04065399. Accessed January 6, 2026. 3. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Acute Myeloid Leukemia V.3.2026. © National Comprehensive Cancer Network, Inc. 2025. All rights reserved. Accessed January 6, 2026. To view the most recent and complete version of the guideline, go online to NCCN.org. 4. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Acute Lymphoblastic Leukemia V.2.2025. © National Comprehensive Cancer Network, Inc. 2025. All rights reserved. Accessed January 6, 2026. To view the most recent and complete version of the guideline, go online to NCCN.org. 5. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Pediatric Acute Lymphoblastic Leukemia V.1.2026. © National Comprehensive Cancer Network, Inc. 2025. All rights reserved. Accessed January 6, 2026. To view the most recent and complete version of the guideline, go online to NCCN.org. 6. Arellano ML, et al. Blood. 2025;146(9):1065-1077.
WARNING: DIFFERENTIATION SYNDROME, QTc PROLONGATION, AND TORSADES DE POINTES
Differentiation syndrome, which can be fatal, has occurred with Revuforj. Signs and symptoms may include fever, dyspnea, hypoxia, pulmonary infiltrates, pleural or pericardial effusions, rapid weight gain or peripheral edema, hypotension, and renal dysfunction. If differentiation syndrome is suspected, immediately initiate corticosteroid therapy and hemodynamic monitoring until symptom resolution.
QTc prolongation and Torsades de Pointes have occurred in patients receiving Revuforj. Correct hypokalemia and hypomagnesemia prior to and during treatment. Do not initiate Revuforj in patients with QTcF >450 msec. If QTc interval prolongation occurs, interrupt, reduce, or permanently discontinue Revuforj.
WARNINGS AND PRECAUTIONS
Differentiation Syndrome: Revuforj can cause fatal or life-threatening differentiation syndrome (DS). Symptoms of DS, including those seen in patients treated with Revuforj, include fever, dyspnea, hypoxia, peripheral edema, pleuropericardial effusion, acute renal failure, rash, and/or hypotension.
In clinical trials, DS occurred in 60 (25%) of 241 patients treated with Revuforj at the recommended dosage for relapsed or refractory acute leukemia. Among those with a KMT2A translocation, DS occurred in 33% of patients with acute myeloid leukemia (AML), 33% of patients with mixed-phenotype acute leukemia (MPAL), and 9% of patients with acute lymphoblastic leukemia (ALL); DS occurred in 18% of patients with NPM1m AML. DS was Grade 3 or 4 in 12% of patients and fatal in 2 patients. The median time to initial onset was 9 days (range 3-41 days). Some patients experienced more than 1 DS event. Treatment interruption was required for 7% of patients, and treatment was withdrawn for 1%.
Reduce the white blood cell count to less than 25 Gi/L prior to starting Revuforj. If DS is suspected, immediately initiate treatment with systemic corticosteroids (e.g., dexamethasone 10 mg IV every 12 hours in adults or dexamethasone 0.25 mg/kg/dose IV every 12 hours in pediatric patients weighing less than 40 kg) for a minimum of 3 days and until resolution of signs and symptoms. Institute supportive measures and hemodynamic monitoring until improvement. Interrupt Revuforj if severe signs and/or symptoms persist for more than 48 hours after initiation of systemic corticosteroids, or earlier if life-threatening symptoms occur such as pulmonary symptoms requiring ventilator support. Restart steroids promptly if DS recurs after tapering corticosteroids.
QTc Interval Prolongation and Torsades de Pointes: Revuforj can cause QT (QTc) interval prolongation and Torsades de Pointes.
Of the 241 patients treated with Revuforj at the recommended dosage for relapsed or refractory acute leukemia in clinical trials, QTc interval prolongation was reported as an adverse reaction in 86 (36%) patients. QTc interval prolongation was Grade 3 in 15% and Grade 4 in 2%. The heart-rate corrected QT interval (using Fridericia’s method) (QTcF) was greater than 500 msec in 10%, and the increase from baseline QTcF was greater than 60 msec in 24%. Revuforj dose reduction was required for 7% due to QTc interval prolongation. QTc prolongation occurred in 21% of the 34 patients less than 17 years old, 35% of the 146 patients 17 years to less than 65 years old, and 46% of the 61 patients 65 years or older. One patient had a fatal outcome of cardiac arrest, and one patient had non-sustained Torsades de Pointes.
Correct electrolyte abnormalities, including hypokalemia and hypomagnesemia, prior to and throughout treatment with Revuforj. Perform an electrocardiogram (ECG) prior to initiation of Revuforj, and do not initiate Revuforj in patients with QTcF >450 msec. Perform an ECG at least once weekly for the first 4 weeks and at least monthly thereafter. In patients with congenital long QTc syndrome, congestive heart failure, electrolyte abnormalities, or those who are taking medications known to prolong the QTc interval, more frequent ECG monitoring may be necessary. Concomitant use with drugs known to prolong the QTc interval may increase the risk of QTc interval prolongation.
- Interrupt Revuforj if QTcF increases >480 msec and <500 msec, and restart Revuforj at the same dose twice daily after the QTcF interval returns to ≤480 msec
- Interrupt Revuforj if QTcF increases >500 msec or by >60 msec from baseline, and restart Revuforj twice daily at the lower dose level after the QTcF interval returns to ≤480 msec
- Permanently discontinue Revuforj in patients with ventricular arrhythmias and in those who develop QTc interval prolongation with signs or symptoms of life-threatening arrhythmia
Embryo-Fetal Toxicity: Revuforj can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment with Revuforj and for 4 months after the last dose of Revuforj.
ADVERSE REACTIONS
Fatal adverse reactions occurred in 9 (4%) patients who received Revuforj, including 4 with sudden death, 2 with differentiation syndrome, 2 with hemorrhage, and 1 with cardiac arrest.
Serious adverse reactions were reported in 184 (76%) patients. The most frequent serious adverse reactions (≥10%) were infection (29%), febrile neutropenia (20%), bacterial infection (15%), differentiation syndrome (13%), and hemorrhage (11%).
The most common adverse reactions (≥20%) including laboratory abnormalities, were phosphate increased (51%), hemorrhage (48%), nausea (48%), infection without identified pathogen (46%), aspartate aminotransferase increased (44%), alanine aminotransferase increased (40%), creatinine increased (38%), musculoskeletal pain (37%), febrile neutropenia (37%), electrocardiogram QT prolonged (36%), potassium decreased (34%), parathyroid hormone intact increased (34%), alkaline phosphatase increased (33%), diarrhea (29%), bacterial infection (27%), triglycerides increased (27%), phosphate decreased (25%), differentiation syndrome (25%), fatigue (24%), edema (24%), viral infection (23%), decreased appetite (20%), and constipation (20%).
DRUG INTERACTIONS
Drug interactions can occur when Revuforj is concomitantly used with:
-
Strong CYP3A4 inhibitors: reduce Revuforj dose
-
Strong or moderate CYP3A4 inducers: avoid concomitant use with Revuforj
-
QTc-prolonging drugs: avoid concomitant use with Revuforj. If concomitant use is unavoidable, obtain ECGs when initiating, during concomitant use, and as clinically indicated. Withhold Revuforj if the QTc interval is >480 msec. Restart Revuforj after the QTc interval returns to ≤480 msec
SPECIFIC POPULATIONS
Lactation: advise lactating women not to breastfeed during treatment with Revuforj and for 1 week after the last dose.
Pregnancy and Testing: Revuforj can cause fetal harm when administered to a pregnant woman. Verify pregnancy status in females of reproductive potential within 7 days prior to initiating Revuforj.
Infertility: based on findings in animals, Revuforj may impair fertility. The effects on fertility were reversible.
Pediatric: monitor bone growth and development in pediatric patients.
Geriatric: no overall differences were observed in the effectiveness of Revuforj between patients who were 65 years and older, and younger patients. Compared to younger patients, the incidences of QTc prolongation and edema were higher in patients 65 years and older.
To report SUSPECTED ADVERSE REACTIONS, contact Syndax Pharmaceuticals at 1-888-539-3REV or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
INDICATIONS
Revuforj® (revumenib) is a menin inhibitor indicated for the treatment of:
-
relapsed or refractory (R/R) acute leukemia with a lysine methyltransferase 2A gene (KMT2A) translocation as determined by an FDA-authorized test in adult and pediatric patients 1 year and older
-
relapsed or refractory acute myeloid leukemia (AML) with a susceptible nucleophosmin 1 (NPM1) mutation in adult and pediatric patients 1 year and older who have no satisfactory alternative treatment options
Please see Full Prescribing Information, including BOXED WARNINGS.
WARNING: DIFFERENTIATION
SYNDROME, QTc
PROLONGATION, AND
TORSADES DE POINTES
Differentiation syndrome, which can be fatal, has occurred with Revuforj. Signs and symptoms may include fever, dyspnea, hypoxia, pulmonary infiltrates, pleural or pericardial effusions, rapid weight gain or peripheral edema, hypotension, and renal dysfunction. If differentiation syndrome is suspected, immediately initiate corticosteroid therapy and hemodynamic monitoring until symptom resolution.