Syndax Presents New Revuforj® (revumenib) Data in Relapsed/Refractory mNPM1 and NUP98r Acute Leukemia from AUGMENT-101 Trial at EHA 2025

Rhea-AI Summary

Syndax Pharmaceuticals presented new data from the AUGMENT-101 trial of Revuforj (revumenib) at EHA 2025, showing promising results in treating relapsed/refractory mNPM1 and NUP98r acute leukemia. In the efficacy-evaluable pivotal R/R mNPM1 AML population (n=77), the treatment achieved a 26% CR+CRh rate and 48% overall response rate. The median overall survival was 4.8 months for all patients, extending to 23.3 months for responders. The drug demonstrated effectiveness across various subgroups, regardless of prior treatments. In Phase 1 R/R NUP98r AML patients, a 60% overall response rate was observed. Revuforj was generally well-tolerated, with only 4.8% of patients discontinuing due to treatment-related adverse events. The drug received FDA approval in November 2024 for R/R acute leukemia with KMT2A translocation.

Positive

• 26% CR+CRh rate and 48% overall response rate in mNPM1 AML patients
• 23.3 months median overall survival in responding patients
• 63% of CR/CRh patients achieved MRD negative status
• 60% response rate in NUP98r AML patients
• Low discontinuation rate of 4.8% due to treatment-related adverse events
• Consistent efficacy across subgroups regardless of prior treatments

Negative

• Relatively short 4.8 months median overall survival in all patients
• Limited duration of CR/CRh response at 4.7 months
• Lower CR+CRh rate (19%) in patients with prior venetoclax exposure compared to 45% in venetoclax-naive patients

Insights

Oncology Clinical Trial Specialist

Syndax's revumenib shows promising 48% response rate in difficult-to-treat mNPM1 AML with encouraging survival data for responders.

The new AUGMENT-101 trial data for Revuforj (revumenib) demonstrates significant clinical activity in relapsed/refractory mutant NPM1 (mNPM1) acute myeloid leukemia (AML), a difficult-to-treat population with limited therapeutic options. The efficacy-evaluable population (n=77) showed a 26% complete remission plus complete remission with partial hematologic recovery (CR+CRh) rate and a 48% overall response rate (ORR).

The data is particularly impressive considering the heavily pretreated nature of the study population - 20% had received four or more prior therapies and 74% had previously received venetoclax. Among responders, 63% achieved minimal residual disease negativity, indicating deep responses. The newly reported median overall survival of 23.3 months for responders represents a substantial improvement over historical outcomes in this population.

The consistent efficacy across subgroups is noteworthy - including similar response rates regardless of co-mutations and prior lines of therapy. While the CR+CRh rate was lower in venetoclax-exposed patients (19% vs 45% in venetoclax-naïve), responses were still observed, suggesting revumenib retains activity in this challenging population.

The early data in NUP98-rearranged AML (60% ORR in 5 patients) points to potential broader utility beyond the currently approved indication in KMT2A-rearranged leukemia. The safety profile remains consistent with previous reports, with only 4.8% of patients discontinuing due to treatment-related adverse events.

With a supplemental NDA already submitted for mNPM1 AML, these data strengthen revumenib's position as a potential standard-of-care for genetically-defined subsets of acute leukemia with significant unmet need.

 – 26% (20/77) CR+CRh rate and 48% (37/77) ORR in efficacy-evaluable pivotal R/R mNPM1 AML population –

– Robust responses observed across subgroups, regardless of co-mutations, number of prior lines of therapy, or prior venetoclax, within efficacy-evaluable pivotal R/R mNPM1 AML population –

– 60% (3/5) ORR in Ph 1 patients with R/R NUP98r AML –

NEW YORK, June 12, 2025 (GLOBE NEWSWIRE) -- Syndax Pharmaceuticals (Nasdaq: SNDX), a commercial-stage biopharmaceutical company advancing innovative cancer therapies, today announced new data from the pivotal AUGMENT-101 trial of Revuforj^® (revumenib), the Company’s first-in-class menin inhibitor, in patients with relapsed or refractory (R/R) mutant NPM1 (mNPM1) and NUP98-rearranged (NUP98r) acute myeloid leukemia (AML). The data are being presented in posters at the 30^th European Hematology Association (EHA) Annual Congress Meeting being held June 12-15, 2025, in Milan, Italy and virtually.

“The new data from AUGMENT-101 continue to highlight Revuforj’s best-in-class profile and its potential to transform the treatment paradigm for acute leukemia patients with certain genetic alterations,” said Nick Botwood, M.B.B.S., Head of Research & Development and Chief Medical Officer at Syndax. “The compelling AUGMENT-101 results led to the FDA approval of Revuforj for R/R acute leukemia with a KMT2A translocation and serve as the foundation for the supplemental NDA we submitted to the FDA for R/R mNPM1 AML, another area of high unmet need.”

“Revumenib has shown a potential best-in-class efficacy profile and the latest data in R/R mNPM1 AML underscore the opportunity for revumenib to become a standard of care treatment for this patient population in addition to R/R KMT2Ar acute leukemia,” said Ibrahim Aldoss, M.D., Associate Professor, Division of Leukemia, Department of Hematology & Hematopoietic Cell Transplantation at the City of Hope. “The revumenib data in R/R mNPM1 AML presented at EHA are impressive, with 26% of patients achieving CR/CRh and nearly 50% achieving an overall response with a medicine that was generally well-tolerated. Furthermore, the 23-month median overall survival observed in responders in a subgroup analysis is very encouraging.”

Additional Results from R/R mNPM1 AML Patients in the Pivotal Phase 2 Portion of the AUGMENT-101 Trial of Revumenib

The Phase 2 portion of the AUGMENT-101 trial of revumenib enrolled 84 patients with R/R mNPM1 AML. As previously reported, the primary endpoint was met in the protocol-defined primary analysis population which included the first 64 adults who met the efficacy evaluable criteria. At EHA 2025, the Company will highlight consistent results from all the efficacy-evaluable R/R mNPM1 AML patients (n=77) in the Phase 2 portion of AUGMENT-101 (DCO: September 2024). In this population, the median age was 63 (11-84), 20% had received four or more prior lines of therapy (median prior lines: 2), and 74% had previously received venetoclax.

The complete remission plus complete remission with partial hematologic recovery (CR+CRh) rate was 26% (20/77; 95% CI: 17%-37%). The median duration of CR/CRh response was 4.7 months (95% CI: 2.1-8.2) and the median time to first CR/CRh was 2.8 months (range: 0.9-8.8). Minimal residual disease (MRD) status was assessed in 19 of 20 patients who achieved CR/CRh, 63% (12/19) of whom were MRD negative. 

The overall response rate (ORR)¹ was 48% (37/77; 95% CI: 37%-60%). Of the patients who achieved an overall response, five patients proceeded to hematopoietic stem cell transplant (HSCT) while in remission, with three patients resuming revumenib after HSCT. Four patients were in CR or CRh and one was in morphologic leukemia-free state (MLFS) when they proceeded to HSCT.

Newly shared data from this single-arm trial show that the median overall survival (OS) observed was 4.8 months (95% CI: 3.4-8.4) among all efficacy-evaluable Phase 2 R/R mNPM1 AML patients, based on the Kaplan-Meier estimate. A new subpopulation analysis that will be reported at a future medical meeting show that a median OS of 23.3 months (95% CI: 8.4-NR) was observed among the 37 patients who achieved an overall response, based on the Kaplan-Meier estimate.

Additionally, newly shared analyses from all efficacy-evaluable Phase 2 R/R mNPM1 AML patients show that CR+CRh responses were observed across subgroups, regardless of co-mutations, number of prior lines of therapy, or prior venetoclax exposure. The CR+CRh rate was 25%, 20%, and 33% among patients with one, two, or three or more prior lines of therapy, respectively. The CR+CRh rate was 45% (95% CI: 23%-69%) among patients without prior venetoclax exposure and 19% (95% CI: 10%-32%) among patients with prior venetoclax exposure.

The AUGMENT-101 Phase 2 safety population included 84 adult and pediatric patients with R/R mNPM1 AML. Detailed results from this safety population were previously published in the journal Blood and will be summarized in the EHA presentation. The safety profile observed with revumenib in this population was consistent with previously reported data. Revumenib was generally well-tolerated with 4.8% (4/84) of patients discontinuing treatment due to treatment-related adverse events. 

Results in R/R NUP98r AML in the Phase 1 Portion of AUGMENT-101 Trial of Revumenib

The Phase 1 portion of the AUGMENT-101 trial of revumenib enrolled R/R acute leukemia patients with KMT2Ar, mNPM1, and other genetic alterations associated with upregulation of HOX, including five patients with NUP98-rearranged (NUP98r) AML. NUP98r is among a growing list of genetic abnormalities associated with upregulation of HOX in leukemia that are susceptible to menin inhibition in preclinical studies.

Among the patients with R/R NUP98r AML, 60% (3/5) attained morphological remission, including one patient who proceeded to transplant, resumed revumenib post-transplant and was in maintenance cycle 10 as of the February 2024 data cutoff date. The safety profile of revumenib in patients with R/R NUP98r AML was consistent with previous reports observed in KMT2Ar or mNPM1 AML.

To further explore the potential for menin inhibition in other genetic populations, a Phase 2 investigator-sponsored study evaluating revumenib in R/R acute leukemia associated with HOX upregulation, including patients with NUP98r AML, has been initiated (NCT06229912). Patients with NUP98r are also included in several other ongoing clinical trials of revumenib, such as the Phase 1 trial of revumenib in combination with intensive chemotherapy in newly diagnosed AML patients and the Phase 1/2 SAVE trial of revumenib in combination with venetoclax and decitabine/cedazuridine in R/R and newly diagnosed patients with AML or mixed-lineage acute leukemia (MPAL). In the SAVE trial, a 100% (5/5) ORR was observed in patients with R/R NUP98r AML (DCO: November 2024).

Additional Revumenib Presentations at EHA 2025

In addition to newly shared data from patients with R/R mNPM1 AML and NUP98r in the AUGMENT-101 trial, an encore presentation of data from patients with R/R KMT2Ar acute leukemia in the pivotal Phase 2 portion of the trial will also be presented. The data will be featured in a poster session titled “Updated Results and Longer Follow-Up From the AUGMENT-101 Phase 2 Study of Revumenib in All Patients with Relapsed or Refractory (R/R) KMT2Ar Acute Leukemia.” Results from the pivotal AUGMENT-101 trial led to the FDA approval in November 2024 of Revuforj^® (revumenib) for the treatment of R/R acute leukemia with a KMT2A translocation in adult and pediatric patients one year and older.

Two other abstracts were accepted for publication-only. One is a ‘trial in progress’ abstract which describes the design of the ongoing Phase 1 study of revumenib in combination with intensive chemotherapy in newly diagnosed AML patients with KMT2Ar, mNPM1, or NUP98r. The second abstract describes real-world treatment patterns in patients with R/R mNPM1 AML in the U.S. between January 2009 and June 2024.

The posters and publication-only abstracts have been published on the virtual EHA congress platform. Copies of the posters will be made available in the ‘Publications & Meetings Presentations’ section of the Syndax website.

About Revuforj^® (revumenib)

Revuforj (revumenib) is an oral, first-in-class, selective menin inhibitor that is FDA approved for the treatment of relapsed or refractory (R/R) acute leukemia with a lysine methyltransferase 2A gene (KMT2A) translocation in adult and pediatric patients one year and older.

Revumenib is in development for the treatment of R/R acute myeloid leukemia (AML) with a nucleophosmin 1 mutation (mNPM1). Positive pivotal data from the AUGMENT-101 trial in this population with revumenib as a monotherapy were recently published and the Company submitted a supplemental NDA for revumenib in R/R mNPM1 AML in April 2025. Additionally, multiple trials of revumenib in combination with standard-of-care agents in mNPM1 AML or KMT2A-rearranged acute leukemia are ongoing or planned across the treatment landscape, including in newly diagnosed patients.

Revumenib was previously granted Orphan Drug Designation for the treatment of AML, ALL and acute leukemias of ambiguous lineage (ALAL) by the U.S. FDA and for the treatment of AML by the European Commission. The U.S. FDA also granted Fast Track designation to revumenib for the treatment of adult and pediatric patients with R/R acute leukemias harboring a KMT2A rearrangement or NPM1 mutation and Breakthrough Therapy Designation for the treatment of adult and pediatric patients with R/R acute leukemia harboring a KMT2A rearrangement.

IMPORTANT SAFETY INFORMATION

WARNING: DIFFERENTIATION SYNDROME

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.

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, and/or hypotension. In clinical trials, DS occurred in 39 (29%) of 135 patients treated with Revuforj. DS was Grade 3 or 4 in 13% of patients and fatal in one. The median time to onset was 10 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: In the clinical trials, QTc interval prolongation was reported as an adverse reaction in 39 (29%) of 135 patients treated with Revuforj. QTc interval prolongation was Grade 3 in 12% of patients. The heart-rate corrected QT interval (using Fridericia’s method) (QTcF) was greater than 500 msec in 8%, and the increase from baseline QTcF was greater than 60 msec in 18%. Revuforj dose reduction was required for 5% of patients due to QTc interval prolongation. QTc prolongation occurred in 16% of the 31 patients less than 17 years old, 33% of the 88 patients 17 years to less than 65 years old, and in 50% of the 16 patients 65 years or older.

Correct electrolyte abnormalities, including hypokalemia and hypomagnesemia, prior to 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 4 (3%) patients who received Revuforj, including 2 with differentiation syndrome, 1 with hemorrhage, and 1 with sudden death.

Serious adverse reactions were reported in 99 (73%) patients. The most frequent serious adverse reactions (≥5%) were infection (24%), febrile neutropenia (19%), bacterial infection (17%), differentiation syndrome (12%), hemorrhage (9%), and thrombosis (5%).

The most common adverse reactions (≥20%) including laboratory abnormalities, were hemorrhage (53%), nausea (51%), phosphate increased (50%), musculoskeletal pain (42%), infection (41%), aspartate aminotransferase increased (37%), febrile neutropenia (35%), alanine aminotransferase increased (33%), parathyroid hormone intact increased (33%), bacterial infection (31%), diarrhea (30%), differentiation syndrome (29%), electrocardiogram QT prolonged (29%), phosphate decreased (25%), triglycerides increased (25%), potassium decreased (24%), decreased appetite (24%), constipation (23%), edema (23%), viral infection (23%), fatigue (22%), and alkaline phosphatase increased (21%).

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.

Pediatric: monitor bone growth and development in pediatric patients.

Geriatric: compared to younger patients, the incidences of QTc prolongation and edema were higher in patients 65 years and older.

Infertility: based on findings in animals, Revuforj may impair fertility. The effects on fertility were reversible.

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.

Please see Full Prescribing Information, including BOXED WARNING.

About Syndax

Syndax Pharmaceuticals is a commercial-stage biopharmaceutical company advancing innovative cancer therapies. Highlights of the Company's pipeline include Revuforj^® (revumenib), an FDA-approved menin inhibitor, and Niktimvo™ (axatilimab-csfr), an FDA-approved monoclonal antibody that blocks the colony stimulating factor 1 (CSF-1) receptor. Fueled by our commitment to reimagining cancer care, Syndax is working to unlock the full potential of its pipeline and is conducting several clinical trials across the continuum of treatment. For more information, please visit www.syndax.com/ or follow the Company on X and LinkedIn.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as "anticipate," "believe," "could," "estimate," "expects," "intend," "may," "plan," "potential," "predict," "project," "should," "will," "would" or the negative or plural of those terms, and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward-looking statements. These forward-looking statements are based on Syndax's expectations and assumptions as of the date of this press release. Each of these forward-looking statements involves risks and uncertainties. Actual results may differ materially from these forward-looking statements. Forward-looking statements contained in this press release include, but are not limited to, statements about the progress, timing, clinical development and scope of clinical trials, the reporting of clinical data for Syndax's product candidates, the acceptance of Syndax and its partners' products in the marketplace, sales, marketing, manufacturing and distribution requirements, and the potential use of its product candidates to treat various cancer indications and fibrotic diseases. Many factors may cause differences between current expectations and actual results, including: unexpected safety or efficacy data observed during preclinical or clinical trials; clinical trial site activation or enrollment rates that are lower than expected; changes to Revuforj's or Niktimvo’s commercial availability; changes in expected or existing competition; changes in the regulatory environment; failure of Syndax's collaborators to support or advance collaborations or product candidates; and unexpected litigation or other disputes. Other factors that may cause Syndax's actual results to differ from those expressed or implied in the forward-looking statements in this press release are discussed in Syndax's filings with the U.S. Securities and Exchange Commission, including the "Risk Factors" sections contained therein. Except as required by law, Syndax assumes no obligation to update any forward-looking statements contained herein to reflect any change in expectations, even as new information becomes available.

All other trademarks are the property of their respective owners.

References

1. Overall response rate (ORR) includes CR, CRh, CRp, CRi, MLFS, and PR; Composite complete remission (CRc) includes CR, CRh, CRp, and CRi.
CR = Complete remission
CRh = Complete remission with partial hematologic recovery
CRp = Complete remission with incomplete platelet recovery
CRi = Complete remission with incomplete count recovery
MLFS = Morphologic leukemia-free state
PR = Partial response

Syndax Contact

Sharon Klahre
Syndax Pharmaceuticals, Inc.
sklahre@syndax.com
Tel 781.684.9827

SNDX-G

FAQ

What are the key efficacy results for Revuforj in treating mNPM1 AML patients?

Revuforj achieved a 26% CR+CRh rate and 48% overall response rate in 77 efficacy-evaluable R/R mNPM1 AML patients, with a median overall survival of 23.3 months in responders.

How well is Revuforj tolerated in patients with acute leukemia?

Revuforj was generally well-tolerated with only 4.8% of patients discontinuing treatment due to treatment-related adverse events in the AUGMENT-101 trial.

What is the effectiveness of SNDX's Revuforj in NUP98r AML patients?

In Phase 1 trials, Revuforj showed a 60% overall response rate in R/R NUP98r AML patients, with one patient proceeding to transplant and maintaining response through 10 cycles of maintenance therapy.

When did Revuforj receive FDA approval and for what indication?

Revuforj received FDA approval in November 2024 for the treatment of R/R acute leukemia with a KMT2A translocation in adult and pediatric patients one year and older.

How does prior venetoclax treatment affect Revuforj's efficacy in mNPM1 AML patients?

Patients without prior venetoclax exposure showed a CR+CRh rate of 45%, while those with prior venetoclax exposure had a lower rate of 19%.