- Data continue to support revumenib's
potential to enhance current standard of care agents -
- 96% CRc (23 of 24 pts) observed in BEAT AML
trial exploring revumenib in combination with
venetoclax/azacitidine in newly diagnosed mNPM1 or KMT2Ar AML
-
- 52% CRc (14 of 27 pts) observed in
AUGMENT-102 trial of revumenib in combination with
fludarabine-cytarabine in acute leukemia patients with R/R mNPM1,
NUP98r or KMT2Ar -
WALTHAM,
Mass., June 14, 2024 /PRNewswire/ -- Syndax
Pharmaceuticals (Nasdaq: SNDX), a clinical stage biopharmaceutical
company developing an innovative pipeline of cancer therapies,
today announced updated data from multiple combination trials of
revumenib, the Company's potent, selective, small molecule menin
inhibitor, in patients with acute leukemias. The updated data are
being presented at the European Hematology Association (EHA) 2024
Congress, being held June 13-16 in
Madrid, Spain and virtually.
"The growing body of data supports the potential for revumenib
to have a meaningful impact in combination with current standard of
care therapies," said Joshua F.
Zeidner, M.D., Chief, Leukemia Research at
the University of North Carolina, Lineberger
Comprehensive Cancer Center. "Based on the BEAT AML data in the
newly diagnosed setting which showed a high rate of MRD-negative
responses coupled with a safety profile that enables combination
use, revumenib has the potential to become a cornerstone of
treatment as front-line therapy for newly diagnosed KMT2Ar and
mNPM1 AML."
"We are committed to advancing revumenib across a spectrum of
acute leukemia patients. As we prepare for the expected
near-term approval of revumenib in the relapsed or refractory
setting, we look forward to providing additional clinical data as
monotherapy and in combination to support treatment in various
acute leukemia treatment settings where novel treatment options are
urgently needed," said Neil Gallagher, M.D., Ph.D.,
President, Head of Research and Development at Syndax.
BEAT AML Trial
The Company announced updated data from the BEAT AML trial of
revumenib in combination with venetoclax/azacitidine in newly
diagnosed mutant nucleophosmin (mNPM1) or KMT2A-rearranged (KMT2Ar)
acute myeloid leukemia (AML) patients aged 60 years or older in an
oral presentation titled "Phase 1b
Study of Azacitidine, Venetoclax and Revumenib in Newly Diagnosed
Older Adults with NPM1 Mutated or KMT2A Rearranged AML: Interim
Results of Dose Escalation from the BeatAML Consortium."
The dose escalation phase of the trial tested revumenib at doses
of 113 mg and 163 mg q12h in combination with a strong CYP3A4
inhibitor beginning on day 1 of a 28-day cycle in combination with
on label doses of venetoclax and azacitidine. As of the data cutoff
date of May 1, 2024, 26 newly diagnosed mNPM1 (n=17) or KMT2Ar
(n=9) AML patients were enrolled. In the efficacy evaluable
population, the composite complete remission1 (CRc) rate
was 96% (23/24) and 92% (22/24) of patients also attained minimal
residual disease (MRD) negative status as determined by central
flow cytometry. Three patients proceeded to hematopoietic stem cell
transplant (HSCT). The first cohort of patients treated in the
trial, at 113 mg, had extended follow-up and an estimated 12-month
survival of 100%.
Revumenib was dosed safely at both the 113 mg and 163 mg q12h
dose in combination with venetoclax and azacitidine. 15% (4/26) of
patients experienced differentiation syndrome with one (4%) Grade 3
event. 46% (12/26) of patients experienced QTc prolongation with
three (12%) Grade 3 events. All DS and QTc prolongations were
self-limiting and resolved without complication or the need for
revumenib dose reductions. Venetoclax was dosed in accordance with
its label and an analysis of the onset and extent of hematologic
toxicities suggest a similar experience to what has been reported
for the venetoclax/azacytidine doublet. Overall, there were no new
or increased safety signals observed when revumenib was added to
this triplet combination.
An expansion cohort is ongoing at both dose levels to establish
the recommended dose for future trials. The Company plans to
initiate a pivotal trial with this combination in front-line newly
diagnosed patients by year-end 2024.
AUGMENT-102 Trial
The Company also announced a poster presentation featuring
updated data from the AUGMENT-102 trial of revumenib in combination
with fludarabine/cytarabine in a predominantly pediatric
population of patients with relapsed/refractory (R/R) mNPM1 (n=2),
NUP98-rearranged (NUP98r) (n=1) or KMT2Ar (n=23) AML titled "Safety
and Activity of Revumenib in Combination with
Fludarabine/Cytarabine (FLA) in Patients with Relapsed/Refractory
Acute Leukemias."
As of the data cutoff date of January 15, 2024, 27 patients
received revumenib plus FLA, including 9 patients treated at 113 mg
q12h and 18 treated at 163 mg q12h. The patients enrolled had
a median age of 6 years and had received a median of 3 prior lines
of therapy. Eighteen (67%) patients had prior FLA containing
regimens while 11 (41%) patients had prior HSCT. Five (56%)
patients treated at the 113 mg q12h dose and nine (50%) patients
treated at the 163 mg q12h achieved a CRc. Most patients who
achieved a CRc and had evaluable data achieved (MRD) negative
status (10/14; 71%) and 7 patients underwent HSCT while in
remission following treatment.
Overall, revumenib was tolerable in heavily pretreated patients
with KMT2Ar, NUP98r, or NPM1m acute leukemias
without increased frequency or severity of AEs compared with
historic FLA data or revumenib monotherapy. One DLT occurred at the
163 mg q12h dose that was a Grade 4 decreased neutrophil count in a
patient with multiple prior transplants.
Grade 3 and above adverse events in over 40% of patients
included decreased platelet count (17/27; 63%), anemia (15/27; 56%)
and febrile neutropenia (13/27; 48%). Lower rates of cytopenias
were reported at the 163 mg q12h dose than the 113 mg q12h dose,
consistent with faster remission at the higher dose. Lower
rates of nonhematologic adverse events were also observed at the
higher dose level, which further suggests that the adverse event
profile was not driven by revumenib. There was one adverse
event leading to death (sepsis at the 113 mg q12h dose level) not
related to revumenib. There were no cases of differentiation
syndrome in the trial.
This study supports the selection of revumenib 163 mg q12h (95
mg/m2 q12h if weight <40 kg) combined with FLA and a strong
cytochrome P450 inhibitor as the RP2D, in line with the dose of
revumenib under FDA review as a monotherapy agent.
Additional Presentations at EHA 2024
In addition to updated results from the BEAT AML and AUGMENT-102
studies, an encore presentation of results from the pivotal
AUGMENT-101 study of revumenib in R/R KMT2Ar acute leukemia were
also featured at the Congress during an oral session titled
"Revumenib Monotherapy in Patients with Relapsed/Refractory KMT2Ar
Acute Leukemia: Topline Efficacy and Safety Results from the
Pivotal AUGMENT-101 Phase 2 Study."
Results from an exploratory analysis of immunophenotypic changes
in AML blasts following treatment with revumenib were also featured
in a poster presentation titled "Characterization of
Immunophenotypic Changes Following Menin Inhibition in Acute
Myeloid Leukemia."
Copies of EHA posters and presentations will be available in the
Publications and Meeting Presentations section of Syndax's
website.
About Revumenib
Revumenib is a potent, selective, 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 ALL and AML,
and mutant nucleophosmin (mNPM1) AML. Positive topline results from
the Phase 2 AUGMENT-101 trial in R/R KMT2Ar acute leukemia showing
the trial met its primary endpoint were presented at the 65th
American Society of Hematology Annual Meeting, and data from the
Phase 1 portion of AUGMENT-101 in acute leukemia was published in
Nature. Revumenib was granted Orphan Drug Designation by the FDA
and European Commission for the treatment of patients with AML and
Fast Track designation by the FDA for the treatment of adult and
pediatric patients with R/R acute leukemias harboring a KMT2A
rearrangement or NPM1 mutation. Revumenib was granted Breakthrough
Therapy Designation by the FDA for the treatment of adult and
pediatric patients with R/R acute leukemia harboring a KMT2A
rearrangement.
About Syndax
Syndax Pharmaceuticals is a clinical stage
biopharmaceutical company developing an innovative pipeline of
cancer therapies. Highlights of the Company's pipeline include
revumenib, a highly selective menin inhibitor, and axatilimab, a
monoclonal antibody that blocks the CSF-1 receptor. For more
information, please visit www.syndax.com or follow
the Company on X (formerly
Twitter) 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, 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 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
1Composite 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
Syndax Contact
Sharon Klahre
Syndax Pharmaceuticals, Inc.
sklahre@syndax.com
Tel 781.684.9827
SNDX-G
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SOURCE Syndax Pharmaceuticals, Inc.
