On June 12, 2025 Syndax Pharmaceuticals (Nasdaq: SNDX), a commercial-stage biopharmaceutical company advancing innovative cancer therapies, reported that data from the BEAT AML trial of revumenib in combination with venetoclax and azacitidine (ven/aza) in newly diagnosed mutant NPM1 (mNPM1) and KMT2A-rearranged (KMT2Ar) acute myeloid leukemia (AML) patients were published in the Journal of Clinical Oncology and simultaneously presented in an oral session at the 30th European Hematology Association (EHA) (Free EHA Whitepaper) Annual Congress Meeting being held June 12-15, 2025, in Milan, Italy and virtually (Press release, Syndax, JUN 12, 2025, View Source [SID1234653848]).

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"The data observed in BEAT AML underscore the potential for revumenib with ven/aza to improve outcomes for newly diagnosed mNPM1 or KMT2Ar AML patients who are not eligible for intensive chemotherapy, a population that continues to face poor long-term outcomes despite recent advances," said Nick Botwood, M.B.B.S., Head of Research & Development and Chief Medical Officer at Syndax. "These data, along with the results from other trials of revumenib in different settings, highlight revumenib’s potential to become a cornerstone therapy for all menin-dependent acute leukemias across the treatment continuum."

"These data support the ability to combine revumenib with ven/aza in the frontline setting and the clinical activity observed highlights the potential for the triplet to provide high rates of complete remission and MRD-negativity, two treatment goals associated with improved clinical outcomes," said Joshua F. Zeidner, M.D., Chief, Leukemia Research at the University of North Carolina, Lineberger Comprehensive Cancer Center and Principal Investigator in the BEAT AML trial. "Overall, the data we observed in BEAT AML are very encouraging and suggest that the ongoing EVOLVE-2 pivotal frontline trial evaluating the triplet in unfit mNPM1 AML patients could deliver practice-changing results."

Summary of Results from BEAT AML Phase 1 Trial

The publication and EHA (Free EHA Whitepaper) presentation report updated results from the Phase 1b BEAT AML trial evaluating the safety and clinical activity of revumenib in combination with venetoclax/azacitidine in newly diagnosed older adults (≥60 years) with mNPM1 or KMT2Ar AML. The trial is being conducted as part of The Leukemia & Lymphoma Society’s Beat AML Master Clinical Trial (NCT03013998).

As of September 2024, 43 patients were enrolled and treated in BEAT AML across two dose levels of revumenib (113 mg q12 or 163 mg q12h with strong CYP3A4 inhibitor azoles) in combination with venetoclax and azacitidine. Overall, 79% (34/43) of patients had mNPM1 AML and 21% (9/43) had KMT2Ar AML. The median age was 70 years (range: 60-92) and 40% were ≥75 years.

Revumenib was generally well tolerated at both dose levels in combination with venetoclax and azacitidine without a maximal tolerated dose identified. The most common overall non-hematologic treatment-emergent adverse events (TEAEs) of any grade were nausea (60%), constipation (53%), QTc prolongation (44%), hypokalemia (44%), and vomiting (42%). Overall Grade ≥3 non-hematologic AEs were rare and similar between both dose levels.

In the intent-to-treat population, the observed rate of complete remission (CR) was 67% (29/43), composite complete remission (CRc) was 81% (35/43), and the overall response rate (ORR) was 88% (38/43). Among 37 patients with measurable residual disease (MRD) response assessment, 100% were MRD negative by centralized flow cytometry testing (sensitivity of 0.02%). The median duration of CRc was 12.0 months (95% CI: 7.8-not reached). 23% (10/43) of patients had proceeded to hematopoietic stem cell transplantation (HSCT) as of the February 2025 data cut off.

In an early analysis of survival from this single-arm trial (median follow-up of 6.9 months), the median overall survival (OS) observed was 15.5 months (95% CI: 9.5-19.5). Subset analysis showed a CRc rate of 77% and an observed median OS of 15.5 months in mNPM1 patients with intermediate risk by ELN 2024 (n=17), and a CRc rate of 89% and observed median OS of 18.0 months in KMT2Ar patients (n=9). In contrast, historical data from newly diagnosed mNPM1 patients with intermediate risk treated with venetoclax and azacitidine show a CRc of 57% and median OS of 9.9 months.1 In newly diagnosed KMT2Ar AML patients treated with venetoclax and hypomethylating agent therapy, a CRc rate of 43% and median OS of 2.5 months was observed in a retrospective analysis.2

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 completed the submission of 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.

On June 12, 2025 SkylineDx, an innovative diagnostics company specializing in molecular diagnostics for oncology, inflammatory, and infectious diseases, reported the publication of new results from the PRospective Observational Multiple Myeloma Impact Study (PROMMIS) in the British Journal of Haematology (Press release, SkylineDx, JUN 12, 2025, View Source [SID1234653864]). The paper prospectively validates SKY92’s prognostic performance using real-world data and assesses its impact on risk classification and (hypothetical) treatment decisions compared to conventional markers. This prospective, real-world study reinforces the clinical utility of the SKY92 gene expression profiling (GEP) classifier in improving risk stratification and guiding treatment decisions in multiple myeloma (MM) patient care.

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Key findings:

A total of 251 newly diagnosed multiple myeloma patients were enrolled in 9 top-tier US cancer centers; this all-comers study allows for a broad and diverse patient population, mimicking the real-world setting.
Progression-Free Survival (PFS) showed a significant difference between the standard- and high-risk groups, while Overall Survival (OS) did not differ significantly based on conventional clinical risk markers.
Risk stratification by SKY92 showed significant differences in both survival PFS and OS endpoints:
– SKY92 standard-risk patients have a 3-year PFS and OS of 66% and 92% respectively
– SKY92 high-risk patients have a 3-year PFS and OS of 39% and 76% respectively
The study demonstrates that integrating SKY92 into routine practice can enhance prognostic accuracy and support personalized treatment planning, marking an important milestone toward the widespread clinical implementation of the SKY92 classifier in MM management. The PROMMIS study was made possible through the close collaboration of nine renowned U.S. hospitals and research centers. Together, these institutions enrolled 251 newly diagnosed multiple myeloma (NDMM) patients between 2018 and 2021. This broad representation underscores the generalizability of the study’s findings to clinical practice. The study prospectively confirmed that SKY92 significantly improves risk stratification over conventional clinical and genetic markers. Patients classified as high risk by SKY92 exhibited significantly shorter PFS and OS, validating the signature’s prognostic strength in real-world data.

After receiving SKY92 results, clinicians revised their initial hypothetical treatment plans in 50% of the cases. By accurately identifying high-risk patients, SKY92 supports more intensive or trial-based treatment approaches for those who need them. At the same time, by accurately identifying standard-risk patients, SKY92 can reduce the overestimation of risk in patients who may not require aggressive treatment, minimizing unnecessary toxicity associated with intensive therapy. The integration of SKY92 into clinical decision-making increased physician confidence in 40% of cases. Clinicians reported greater certainty and objectivity when interpreting complex risk profiles, leading to improved alignment of treatment with patient prognosis.

"These findings offer strong evidence that SKY92 can help clinicians better define high-risk multiple myeloma patients, enabling more targeted and appropriate therapeutic strategies," said Dr. Noa Biran, M.D., study investigator and Associate Professor at Hackensack Meridian School of Medicine.

"This publication confirms years of scientific work and collaboration," said Jvalini Dwarkasing, PhD, Chief Scientific Officer at SkylineDx. "The SKY92 signature brings molecular precision to the clinic, giving physicians a powerful tool to reduce uncertainty in a highly complex disease. It’s incredibly rewarding to see its positive impact on real-world patient care".

The results from the PROMMIS study underscore the powerful role SKY92 can play in modernizing risk stratification and guiding personalized treatment decisions for multiple myeloma patients. By providing molecular-level insights that outperform traditional risk assessment tools, SKY92 supports clinicians in delivering more precise, confident, and effective care. This study brings us one step closer to making precision medicine a standard in hematology and reaffirms SkylineDx’s commitment to improving patient outcomes through innovation in diagnostics.

About SKY92

Multiple Myeloma is a heterogeneous disease, and its course can vary significantly between patients. The SKY92 biomarker enhances biological insights into the disease. This molecular diagnostic test measures the activity of 92 genes in the malignant myeloma plasma cells and determines how aggressive the myeloma is. When myeloma is more aggressive (high-risk disease) it is less likely to respond to conventional treatments and the patient might benefit from intensification of therapy. The test is CE-IVD registered in Europe and available as laboratory developed test (LDT) from SkylineDx’s CAP/CLIA lab in San Diego (CA, USA).

On June 12, 2025 Scenic Biotech reported the extension of its research collaboration with Bristol Myers Squibb (Press release, Scenic Biotech, JUN 12, 2025, View Source [SID1234653832]). The growth of this partnership highlights the unique power of our Cell-Seq platform, which unlocks the underlying genetic interactions of cellular pathways for novel drug targets.

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Together, we are working to identify target biology for indication selection, and expansion, driving progress towards novel treatments for severe diseases. It’s a testament to the productive collaboration and shared vision between our teams.

In parallel to advancing our proprietary pipeline in neuro- and metabolic diseases, we remain committed to supporting our partners in shaping the future of medicine and improving patient outcomes. We look forward to the continued progress we’ll make together!

On June 12, 2025 Syndax Pharmaceuticals (Nasdaq: SNDX), a commercial-stage biopharmaceutical company advancing innovative cancer therapies, reported 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) (Press release, Syndax, JUN 12, 2025, View Source [SID1234653849]). The data are being presented in posters at the 30th European Hematology Association (EHA) (Free EHA Whitepaper) Annual Congress Meeting being held June 12-15, 2025, in Milan, Italy and virtually.

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"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 (Free EHA Whitepaper) 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 (Free EHA Whitepaper) 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 (Free EHA Whitepaper) 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 (Free EHA Whitepaper) 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 (Free EHA Whitepaper) 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.

On June 12, 2025 InnoCare (HKEX: 09969; SSE: 688428) reported its robust oncology pipeline was presented at the ongoing European Hematology Association (EHA) (Free EHA Whitepaper) 2025 Congress (Press release, InnoCare Pharma, JUN 12, 2025, View Source [SID1234653865]).

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Poster Presentation:

1. First Presentation of Efficacy and Safety Data for First-Line Treatment of CLL/SLL with BCL2 Inhibitor Mesutoclax in Combination with BTK Inhibitor Orelabrutinib (Abstract No.: PS1567)

The study showed that mesutoclax (100 and 125 mg) in combination with orelabrutinib was safe and well tolerated in patients with treatment naïve (TN) CLL/SLL. Substantial efficacy was observed, with early high undetectable MRD (uMRD) rate.

42 patients with TN CLL/SLL were enrolled (mesutoclax 100 mg, n=21; 125 mg, n=21). The fixed-duration treatment of mesutoclax in combination with orelabrutinib is expected to deliver deeper remissions for TN CLL/SLL patients. In all patients, the overall response rate (ORR) was 97.6%.

At week 24 of the combination therapy, in the 125 mg dose cohort, the overall response rate (ORR) was 100%, the complete remission rate (CRR) was 23.8%, the CRR in target lesions was 57.1%, and the peripheral blood (PB) uMRD rate was 48%. In the 100 mg mesutoclax dose cohort, the ORR was 95.2%, the CRR was 19.0%, the CRR in target lesions was 42.9%, and the PB uMRD rate was 19%. With the extension of the duration of treatment, the therapeutic efficacy is expected to be further improved.

All patients are still on treatment. No disease progression or death occurred, and no adverse events leading to discontinuation of treatment were reported.

Due to its favorable efficacy and safety profile, a registrational Phase III clinical study of mesutoclax (125 mg once daily) in combination with orelabrutinib for the treatment of TN CLL/SLL patients has been initiated, with patient enrollment being accelerated.

2. Orelabrutinib Combined with Bendamustine-Rituximab or Obinutuzumab followed by Orelabrutinib Maintenance in Untreated Marginal Zone Lymphoma (OPTIMIZE): A Multicenter, Single-Arm, Phase II Study (Abstract No.: PF898)

The absence of a standard first-line treatment for marginal zone lymphoma (MZL) have inspired the exploration of novel regimens. In recent years, Bruton’s tyrosine kinase inhibitors (BTKis) have demonstrated durable responses with a favorable benefit-risk profile across all MZL subtypes in the relapsed/refractory setting. Orelabrutinib is a novel BTK inhibitor with higher selectivity and fewer off-target than other BTK inhibitors. Orelabrutinib combined with bendamustine-rituximab or obinutuzumab followed by orelabrutinib maintenance was effective and well-tolerated in untreated patients with MZL.

The majority of patients presented with MALT lymphoma and had Ann Arbor stage II-IV disease. At the end of induction treatment, the overall response rate (ORR) was 100.0% among all enrolled patients. At the data cutoff, the median progression-free survival (PFS) and overall survival (OS) remained immature. No BTK inhibitor-related adverse events (AEs), such as atrial fibrillation or bleeding, were observed.

3. The Rationality, Efficacy and Safety of Orelabrutinib plus Obinutuzumab (O2) in Systemic Treatment-naïve Marginal Zone Lymphoma: A Prospective Cohort Study (Abstract No.: PS1902)

The Orelabrutinib plus Obinutuzumab regimen had well rationality and demonstrated promising efficacy.

Across the entire study and during the period of induction therapy, the best objective response rate (ORR) was 100%. 3 patients who achieved partial response (PR) after the induction therapy subsequently achieved complete response (CR) in the maintenance period. The 18-month progression-free survival (PFS) and overall survival (OS) rates were both 100%.

4. Ultra-low Dose Radiotherapy Combined with Orelabrutinib Improves the Complete Response Rate of Treatment for Localized Ocular Adnexal Extranodal Marginal Zone B-cell Lymphoma (Abstract No.: PS1901)

The combination of ultra-low dose radiotherapy and orelabrutinib in the treatment of ocular adnexal extranodal marginal zone lymphoma (OA-EMZL) not only improves the effectiveness of treatment but also significantly reduces the toxic effects of radiotherapy, providing a new approach for the treatment of localized OA-EMZL.

Of all the 17 patients who completed treatment, 16 patients achieved complete response (CR) and one patient achieved a partial response. Additionally, the lesions in the patients still undergoing treatment have shrunk compared to before treatment.

5. Orelabrutinib plus Bendamustine-Rituximab (OBR) versus Bendamustine-Rituximab (BR) in Transplant-ineligible, Intermediate- to High-risk Mantle Cell Lymphoma (MCL) (Abstract No.: PS1969)

This open-label, randomized, multi-center study aims to compare the efficacy and safety of Orelabrutinib plus Bendamustine-Rituximab versus Bendamustine-Rituximab in transplant-ineligible, intermediate- to high-risk mantle cell lymphoma (MCL) patients. Early data suggest that Orelabrutinib plus Bendamustine-Rituximab could reduce disease progression events compared to Bendamustine-Rituximab in high-risk MCL. Updated outcomes on efficacy, safety, and biomarker analysis will be reported.

6. Pomalidomide, Rituximab, Orelabrutinib, and MiniCHOP-like (PRO-miniCHOP) in Elderly Patients with Newly Diagnosed Diffuse Large B-cell Lymphoma: Updated Results from a Phase II Study (Abstract No.: PF950)

The results further support Pomalidomide, Rituximab, Orelabrutinib, and MiniCHOP-like (PRO-miniCHOP) as a potential treatment option for elderly patients with diffuse large B-cell lymphoma (DLBCL), demonstrating promising efficacy and acceptable safety, especially for those who responded to the Pomalidomide-Rituximab-Orelabrutinib (PRO) induction therapy.

A total of 32 patients were enrolled in this study, of whom 26 patients completed ≥3 cycles of the PRO-miniCHOP, resulting in a complete response rate (CRR) of 65.4% and overall response rate (ORR) of 100.0%. Among the 21 patients who completed the full 6-cycle therapy with PRO-miniCHOP, both the CRR and ORR were 95.2%. At a median follow-up of 15.6 months, the median progression-free survival (PFS) and overall survival (OS) had not yet been reached, with the 2-year PFS and OS rates being 94.7% and 100.0%, respectively.

7. Orelabrutinib Addition to R-CHOP-like Regimen Adapted to Response in Treatment-Naïve Non-GCB DLBCL: Update Results of Orient Study (Abstract No.: PS1943)

In non-germinal center B-cell-like (non-GCB) diffuse large B-cell lymphoma (DLBCL) patients who responded to orelabrutinib plus rituximab (OR) induction, orelabrutinib plus R-CHOP-like (OR-CHOP) exhibited favorable antitumor activity and manageable safety. Update results further support the orelabrutinib plus R-CHOP-like therapy as an option in this disease.

At end of 6-cycle orelabrutinib plus R-CHOP-like, response (all 100%) was independent of double-expressing lymphoma (DEL), extranodal involvement (EI), and Lymphgen subtypes. No off-target-related cardiac toxicities occurred.

8. Primary Efficacy and Safety of First-line R-MTO Regimen (Rituximab, Methotrexate, Thiotepa, and Orelabrutinib) followed by Autologous Hematopoietic Stem Cell Transplantation in PCNSL (Abstract No.: PF966)

The Rituximab, Methotrexate, Thiotepa, and Orelabrutinib (R-MTO) induction treatment has demonstrated notable efficacy in achieving higher response rate among patients with newly diagnosed primary central nervous system lymphoma (PCNSL), with a manageable safety profile.

At the data cutoff, all patients had completed four cycles of induction therapy, and the complete response (CR) rate and overall response rate (ORR) were 93.34% and 96.67%, respectively. The 12-month progression-free survival (PFS) and overall survival (OS) rates were 82.26% and 85.33%, respectively.

9. Orelabrutinib, Rituximab Combined with High-Dose Methotrexate as Induction Therapy in Newly Diagnosed Primary Central Nervous System Lymphoma (Abstract No.: PS1917)

This study demonstrated the promising efficacy of the Orelabrutinib, Rituximab Combined with High-Dose Methotrexate induction regimen in newly diagnosed primary central nervous system lymphoma (PCNSL), with encouraging response rates and durable progression-free survival (PFS). The regimen also showed promising overall survival (OS) trends, highlighting its potential as an effective treatment. Treatment-related adverse events (TRAEs) were manageable, and no severe BTK inhibitor-related off-target toxicities (e.g., atrial fibrillation/flutter) were observed. These findings suggest that the Orelabrutinib, Rituximab Combined with High-Dose Methotrexate regimen is a well-tolerated and effective therapeutic option for PCNSL.

Except the above poster presentations, more than 10 studies were also selected as poster presentations or online publications at the meeting. For more detailed clinical data, please refer to EHA (Free EHA Whitepaper) website.