– New monotherapy and combination data in
acute leukemia further highlight revumenib's compelling clinical
profile –
– 64% ORR (62/97) in expanded dataset of
patients with R/R KMT2Ar acute leukemia in Ph 2 AUGMENT-101 pivotal
cohort –
– 88% ORR (23/26) in SAVE trial testing
revumenib, venetoclax and decitabine/cedazuridine combination in
R/R AML –
WALTHAM,
Mass., Nov. 5, 2024 /PRNewswire/ -- Syndax
Pharmaceuticals (Nasdaq:SNDX) today announced that multiple
abstracts evaluating revumenib, an oral small molecule menin
inhibitor, have been accepted for oral presentation at the
66th American Society of Hematology (ASH) Annual Meeting
being held in San Diego,
California, December 7-10,
2024. The oral presentations will highlight data evaluating
the safety and efficacy of revumenib as monotherapy or in
combination for the treatment of patients with acute leukemias.
Copies of the abstracts are now available online on the ASH
website.
"The data being presented this year at ASH demonstrate Syndax's
commitment to develop revumenib as a practice-changing therapy for
adult and pediatric patients with acute leukemias," said
Neil Gallagher, M.D., Ph.D.,
President, Head of Research and Development at Syndax. "We look
forward to presenting these data and continuing to rapidly advance
the development of revumenib for adult and pediatric acute leukemia
patients who may respond to menin inhibition, such as patients with
KMT2Ar or mNPM1 alterations."
The FDA has granted Priority Review for the New Drug Application
(NDA) for revumenib for the treatment of adult and pediatric
patients with relapsed or refractory (R/R) KMT2A-rearranged
(KMT2Ar) acute leukemia. The NDA is being reviewed under the FDA's
Real-Time Oncology Review Program (RTOR) and has a Prescription
Drug User Fee Act (PDUFA) target action date of December 26, 2024.
In March 2024, the Company
announced the completion of enrollment in the final AUGMENT-101
pivotal trial cohort in patients with R/R mutant nucleophosmin
(mNPM1) acute myeloid leukemia (AML). Topline data is expected in
the fourth quarter of 2024 and could support a supplemental NDA
filing for revumenib in R/R mNPM1 AML in the first half of
2025.
The Company will host an in-person investor event, along with a
live webcast, to discuss the latest data supporting the Company's
pipeline on Monday, December 9, 2024
at 7:00 a.m. PT/ 10:00 a.m. ET during the ASH Annual
Meeting. The live webcast will be available on the Investor
section of the Company's website at www.syndax.com, where a replay
of the event will also be available for a limited time.
Overview of Abstracts Accepted for Presentation at
66th ASH Annual Meeting
New Data from Phase 2 Portion of the AUGMENT-101 Trial of
Revumenib in R/R KMT2Ar Acute Leukemia
Syndax previously presented positive data from the
protocol-defined interim analysis of the pivotal Phase 2 portion of
the AUGMENT-101 trial of revumenib in adult and pediatric patients
with R/R KMT2Ar AML and acute lymphoid leukemia (ALL). The trial
met its primary endpoint at the protocol-defined interim analysis
with a complete remission (CR) or a CR with partial hematological
recovery (CRh) rate of 23% (13/57; 95% CI: 12.7-35.8; one-sided
p-value = 0.0036) among the 57 efficacy evaluable patients in the
KMT2Ar cohort as of the July 2023
data cutoff (DCO) date.
This updated analysis (DCO: February
2024) includes 116 patients in the Phase 2 safety population
(an increase of 22 patients who were enrolled and treated with
revumenib after the previous July
2023 DCO), and 97 patients in the Phase 2 efficacy
population (an increase of 40 patients who were newly enrolled or
who reached sufficient follow-up after the previous July 2023 DCO).
Within this larger efficacy population of patients with R/R
KTM2Ar acute leukemia from the Phase 2 portion of the AUGMENT-101
trial (n=97), 23% (22/97) of patients achieved CR/CRh (95% CI:
15%-32%). The CRc rate was 42% (95% CI: 32%-53%) and the ORR was
64% (95% CI: 54%-73%). Among patients with measurable residual
disease (MRD) results available, 61% (11/18) of CR/CRh responders
and 58% (21/36) of CRc responders achieved MRD negativity. Of the
62 patients who achieved ORR, 34% (21/62) proceeded to
hematopoietic stem cell transplantation (HSCT). Nine patients
resumed revumenib post-HSCT.
The median duration of response among the 22 CR/CRh responders
was 6.4 months (95% CI: 1.9 mo-NR). Of note, among the 13 CR/CRh
responders from the interim analysis, the median duration of CR/CRh
extended to 13.0 months (95% CI: 3.4 mo–NR) after seven additional
months of follow-up (DCO: February
2024). Five of these patients remained in follow-up with no
relapse or death as of the data cutoff.
Within the larger safety population of patients with R/R KTM2Ar
acute leukemia from the Phase 2 portion of the AUGMENT-101 trial
(n=116), revumenib was generally well tolerated and the safety
profile was consistent with the Company's previously reported data.
Treatment-emergent adverse events (TEAEs) and treatment-related
adverse events (TRAEs) leading to treatment discontinuation were
low at 14% (16/116) and 5% (6/116), respectively. The most common
Grade ≥3 TEAEs were consistent with previously reported data. Grade
3 treatment-emergent differentiation syndrome (DS) was observed in
14% (16/116) of patients and one patient (1%) experienced a Grade 4
DS. Grade 3 treatment-emergent QTc prolongation was observed in 13%
(15/116) of patients, with no Grade 4 or Grade 5 events.
Details for the oral presentation are as follows:
Abstract Number: 211
Title: 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
Presenter: Ibrahim Aldoss, M.D.
Session Name: 616. Acute Myeloid Leukemias:
Investigational Drug and Cellular Therapies: Menin Inhibitors in
AML
Session Date: Saturday, December 7, 2024
Session Time: 2:00 PM - 3:30
PM
Presentation Time: 2:00 PM
New Results from Phase 1/2 SAVE Trial of Revumenib in
Combination with Venetoclax and Decitabine/Cedazuridine in R/R
AML
The Phase 1/2 SAVE trial is an investigator-sponsored trial
testing an all-oral regimen of revumenib, venetoclax and the
hypomethylating agent (HMA) ASTX727 (decitabine/cedazuridine) in
children and adults with R/R AML or mixed-lineage acute leukemia
(MPAL) harboring either KMT2Ar, NUP98r or mNPM1 alterations.
As of the latest data cutoff (July
2024), 26 patients were enrolled in the trial. The median
age was 35 years (range: 12-79). At baseline, 11 patients (42%) had
KMT2Ar, 10 patients (38%) had mNPM1, and five patients (20%) had
NUP98r. The median prior lines of therapy was three (range: 1-5);
17 patients (65%) had prior venetoclax, 11 (42%) had prior HSCT,
and two had received a prior menin inhibitor.
The all-oral combination resulted in high rates of remission in
patients with R/R KMT2Ar, mNPM1, or NUP98r AML. The ORR was 88%
(23/26), with a CR/CRh rate of 58% (15/26). MRD status was
available in 14 of the 15 patients who achieved a CR/CRh, 93%
(13/14) of whom were MRD negative. In patients with MRD
status available who achieved a response, 74% (17/23) were MRD
negative. Twelve patients (46%) received HSCT following this
combination, with three patients resuming revumenib post-HSCT.
With a median follow-up of 6.6 months, the 6-month relapse-free
survival was 59% (95% CI: 26%-81%) and overall survival was 74%
(95% CI: 39%-83%). The median duration of response in those with
CR/CRh was not reached. Two patients had completed maintenance
post-HSCT and remained in remission at the time of the data
cutoff.
The combination was generally well tolerated. The most common
(>20%) Grade ≥3 TEAEs were febrile neutropenia (46%) and lung
infection (42%), while Grade ≥3 TRAEs (any agent) were
thrombocytopenia (12%), neutropenia (8%), QT prolongation (8%), and
DS (4%). No patient experienced Grade 4 or 5 DS, and all DS
events were resolved with steroids.
In addition to the R/R cohort, a frontline cohort is now
enrolling patients.
Details for the oral presentation are as follows:
Abstract Number: 216
Title: Phase I/II Study of the All-Oral Combination of
Revumenib (SNDX-5613) with Decitabine/Cedazuridine (ASTX727) and
Venetoclax (SAVE) in R/R AML
Presenter: Ghayas C.
Issa, M.D.
Session Name: 616. Acute Myeloid Leukemias:
Investigational Drug and Cellular Therapies: Menin Inhibitors in
AML
Session Date: Saturday, December 7, 2024
Session Time: 2:00 PM - 3:30
PM
Presentation Time: 3:15
PM
Initial Results from INTERCEPT Trial of Revumenib as
Pre-Emptive Therapy for MRD Positive AML
INTERCEPT is an investigator-sponsored platform trial evaluating
the use of novel therapies, including revumenib, to target MRD and
early relapse in AML. This proof-of-concept trial is exploring
whether targeting MRD in patients with progressive AML may be
an effective approach to maintaining patients in first (CR1)
or second remission (CR2).
As of the July 2024 data cut off,
nine patients with MRD relapse (eight with mNPM1 and one with
KMT2Ar) were enrolled in the safety cohort and received revumenib.
The median age was 62 years; seven were in CR1, two in CR2; three
had prior venetoclax exposure and six had prior intensive
therapy.
In a preliminary analysis of the eight mNPM1 patients who
received revumenib, five of the eight patients had MRD reduction,
including three who achieved MRD negativity within six cycles. In
the nine-patient safety cohort, dose-limiting toxicities included
reversible Grade 3 QTc prolongation in two patients; neither
de-escalation nor elimination were mandated and 276 mg of revumenib
BID was therefore considered safe for further expansion. These data
support revumenib's safety profile and activity in patients with
mNPM1 MRD relapse.
Details for the oral presentation are as follows:
Abstract Number: 223
Title: Revumenib as Pre-emptive Therapy for Measurable
Residual Disease in NPM1 mutated or KMT2A-rearranged Acute Myeloid
Leukemia: A Domain of the Multi-Arm ALLG AMLM26 Intercept Platform
trial
Presenter: Sun Loo,
M.B.B.S.
Session Name: 619. Acute Myeloid Leukemias:
Disease Burden and Minimal Residual Disease in Prognosis and
Treatment: Measurable Residual Disease in AML in 2024 and
Beyond
Session Date: Saturday, December
7, 2024
Session Time: 2:00 PM - 3:30
PM
Presentation Time: 2:00
PM
About Revumenib
Revumenib is an oral, small molecule
inhibitor of the menin-KMT2A binding interaction that is being
developed for the treatment of KMT2A-rearranged (KMT2Ar), also
known as mixed lineage leukemia rearranged or MLLr, acute leukemias
including acute lymphoid leukemia (ALL) and acute myeloid
leukemia (AML), and mutant NPM1 AML. The Journal of Clinical
Oncology published results from the Phase 2 AUGMENT-101 trial
of revumenib in R/R KMT2Ar acute leukemia showing the trial met its
primary endpoint.
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.
About Syndax
Syndax Pharmaceuticals is a
commercial-stage biopharmaceutical company developing an innovative
pipeline of cancer therapies. Highlights of the Company's
pipeline include revumenib, a selective 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 (formerly Twitter) and LinkedIn.
Syndax 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
"may," "will," "expect," "plan," "anticipate," "estimate,"
"intend," "believe" 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 our 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 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.
References
1 Overall response rate 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
sklahre@syndax.com
Tel 781.684.9827
SNDX-G
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SOURCE Syndax Pharmaceuticals, Inc.