- Data collectively highlight revumenib's combination
potential with current standard of care agents and support
advancement into pivotal combination trials in the frontline
setting -
- 100% CRc observed in BEAT AML trial exploring revumenib in
combination with venetoclax/azacitidine in newly diagnosed mNPM1 or
KMT2Ar AML -
-78% CRc observed in SAVE AML trial, an all-oral combination
of revumenib, venetoclax and
decitabine/cedazuridine in R/R mNPM1, NUP98r and KMT2Ar
AML; five of nine patients continue in remission, 2 beyond
11 months at the time of the data cut -
- 33% CRc observed in AUGMENT-102 trial of revumenib in
combination with fludarabine-cytarabine in pediatric R/R mNPM1,
NUP98r and KMT2Ar AML -
- Revumenib was well tolerated with no new safety signals
identified beyond those observed with the respective SOC
combinations -
WALTHAM,
Mass., Dec. 11, 2023 /PRNewswire/ -- Syndax
Pharmaceuticals (Nasdaq: SNDX), a clinical stage biopharmaceutical
company developing an innovative pipeline of cancer therapies,
today announced data from multiple trials of revumenib in
combination with standard of care agents in patients with
nucleophosmin mutant (mNPM1) and KMT2A-rearranged (KMT2r)
relapsed/refractory (R/R) acute leukemias. Revumenib is the
Company's highly selective, oral menin inhibitor.
Data to date demonstrate that revumenib has been well tolerated
and demonstrated clinical activity in combination with
venetoclax/hypomethylating agents in both the frontline and R/R
acute myeloid leukemia (AML) settings, as well as in combination
with fludarabine/cytarabine (FLA) chemotherapy in a heavily
pretreated R/R pediatric AML population, including in patients who
relapsed on FLA. In all three trials, patients are now
receiving the full monotherapy recommended Phase 2 dose in
combination with the standard of care agents. The new combination
data collectively highlight revumenib's potential to safely combine
with current standard of care agents across the acute leukemia
treatment landscape, and support expansion of ongoing trials and
advancement into additional combination trials currently in
planning.
"Given the urgent need for novel, effective solutions for acute
leukemia patients, we're excited to show clinical data
demonstrating tolerability and compelling clinical responses when
revumenib is added to current treatment regimens," said
Michael A. Metzger, Chief Executive
Officer. "The potential to safely combine with standard of care
positions revumenib to become a cornerstone of treatment across a
range of acute leukemia populations. In addition,
current response rates seen across all three trials strengthen
revumenib's already robust clinical profile as a monotherapy and
furthers our conviction that revumenib could be a first- and
best-in-class treatment for both KMT2Ar and mNPM1 acute
leukemias."
SAVE AML Trial
Results from the SAVE AML trial of revumenib in combination with
venetoclax-decitabine/cedazuridine in R/R AML were featured during
an oral session at the 65th American Society of
Hematology (ASH) Annual Meeting. The dose escalation phase of the
trial tested revumenib at doses of 113 mg and 163 mg every 12 hours
(q12h) in combination with azole antifungals known to strongly
inhibit CYP3A4 enzymes. As of a data cutoff date of
November 1, 2023, nine patients with
KMT2Ar, mNPM1 or NUP98r AML or mixed phenotypic acute leukemia
(MPAL) were enrolled and response evaluable at the time of the data
cut. Patients received a median of three prior lines of
therapy, including 56% who received prior venetoclax and 67% who
received prior hypomethylating agents (HMA) or underwent prior stem
cell transplant or both.
All nine patients attained a morphologic remission for an
overall response rate of 100%, 78% of whom achieved a
CRc1 including 44% who achieved a CR/CRh. 67% (6/9) of
patients in the trial attained minimal residual disease (MRD)
negative status. Five patients transitioned to hematopoietic
stem-cell transplantation (HSCT) following response. Two patients
initiated post-transplant maintenance with revumenib and continue
in remission for over 11 months.
The combination was well tolerated in this relapsed and
refractory population, with no new safety signals observed beyond
those reported for venetoclax-HMA. Grade ≥3 treatment related
adverse events (TRAEs) included febrile neutropenia (56%),
decreased platelets count (22%), decreased neutrophil count (22%)
and lung infection (22%). There was one dose-limiting toxicity
(DLT) at each dose level, Grade 4 thrombocytopenia that resolved
after a dosing hold. There were no deaths due to TRAEs and no Grade
3 or higher QTc prolongation occurred.
BEAT AML Trial
The Company also announced data from the BEAT AML trial of
revumenib in combination with venetoclax/azacitidine in newly
diagnosed mNPM1 or KMT2Ar AML patients. The dose escalation phase
of the trial tested revumenib at doses of 113 mg and 163 mg q12h in
combination with azole antifungals known to strongly inhibit CYP3A4
enzymes. As of the data cutoff date of December 1, 2023, 13 newly diagnosed mNPM1 (n=8)
or KMT2Ar (n=5) AML patients were efficacy evaluable. In the
efficacy evaluable population, the CRc was 100% (13/13) after 1 – 2
cycles of induction. Eleven (85%) of 13 patients attained a CR/CRh
and 92% (12/13) attained MRD negative status. Two patients
proceeded to transplant.
No new safety signals were identified when revumenib was added
to the standard venetoclax/azacitidine doublet in newly diagnosed
AML patients. One patient at the lowest dose level, 113 mg q12h,
experienced a DLT of decreased platelet counts; no DLTs were
observed in the 163 mg q12h dose cohort. 31% of patients
experienced differentiation syndrome or QTc prolongation, each
included one (8%) Grade 3 event. All were managed without dose
reductions. Cytopenias were manageable across the treatment
experience with continuous dosing of venetoclax and revumenib.
There were no increased safety issues outside of known adverse
events reported for venetoclax/azacitidine toxicities.
An expansion cohort is planned to further evaluate safety and
activity of this combination, and the full BEAT AML data will be
presented at a future medical conference.
AUGMENT-102 Trial
The Company announced data from the AUGMENT-102 trial of
revumenib in combination with fludarabine/cytarabine in a
predominantly pediatric relapsed/refractory mNPM1 (n=1), NUP98r
(n=1) and KMT2Ar (n=13) AML population. The dose-escalation phase
of the trial tested revumenib at doses of 113 mg and 163 mg every
12 hours in combination with azole antifungals known to strongly
inhibit CYP3A4 enzymes. As of the data cutoff date of
September 20, 2023, 15 AML patients
were efficacy evaluable, including three patients treated at 113 mg
q12h and 12 patients treated at 163 mg q12h. The 163 mg q12hr
cohort was comprised of primarily pediatric patients (median age of
four), who had received a median of four prior lines of therapy.
Across both dose groups, 50% of patients had failed prior treatment
with fludarabine/cytarabine. Among the 12 patients treated at
163 mg q12h, four (33%) patients achieved a CRc including three
(25%) patients that achieved a CR; four (33%) proceeded to
transplant, including one mNPM1 patient who received a five-day
course of decitabine prior to transplant.
The triplet of revumenib-fludarabine-cytarabine had an adverse
event profile consistent with that observed with
fludarabine-cytarabine alone, and no new safety signals were
identified in the trial. Grade ≥3 TRAEs in over 30% of patients
included decreased platelets (53%), decreased white blood cells
(40%) and anemia (33%).
Copies of the ASH presentations are available in
the Publications and Meeting Presentations section of
Syndax's website.
Syndax Corporate Event
The above combination data, along with other data presented
through today at the 65th ASH Annual Meeting being held
in San Diego, CA for both the
revumenib and axatilimab clinical programs, will be highlighted at
the Company's investor event on Monday,
December 11, 2023 at 7:00 a.m.
PT/10:00 a.m. ET. The
live audio webcast and accompanying slides for the event may be
accessed through the Events & Presentations page in
the Investors section of the Company's website or directly through
the meeting link here.
For those unable to participate in the conference call or
webcast for the event, a replay will be available on the Investors
section of the Company's website at www.syndax.com for a
limited time.
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, also known as mixed lineage leukemia
rearranged or MLLr, acute leukemias including ALL and AML, and
NPM1-mutant AML. 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 BTD by the FDA for the treatment of adult and
pediatric patients with R/R acute leukemia harboring a KMT2A
rearrangement. Syndax expects to complete an NDA submission for
KMT2Ar acute leukemia under the Oncology Center of Excellence
Review RTOR Program by year-end 2023.
About KMT2A (MLL) Rearranged Acute Leukemia
Rearrangements of the KMT2A (mixed lineage leukemia or MLL) gene
give rise to KMT2Ar acute leukemia that is known to have a poor
prognosis. KMT2A genes produce fusion proteins that require
interaction with the protein called menin to drive leukemic cancer
growth. Disruption of the menin-KMT2Ar interaction has been shown
to halt the growth of KMT2Ar leukemic cells. KMT2Ar acute
leukemia can phenotypically appear as AML, ALL, or mixed
phenotype acute leukemia (MPAL) and is routinely diagnosed through
currently available cytogenetic or molecular diagnostic
techniques. The median overall survival (OS) after standard of
care first-line treatment, including intensive chemotherapy and
transplant, is less than one year and the majority of patients
suffer relapse within five years. With third line treatment or
beyond, less than 5% of patients achieve complete remission (CR),
and the median OS is less than three months. There are currently no
approved therapies indicated for KMT2A-rearranged acute
leukemia.
About NPM1-Mutant Acute Myeloid Leukemia
NPM1-mutant AML, which is distinguished by mutations in the NPM1
gene that drive the leukemic phenotype, is the most common type of
cytogenetically normal adult AML and represents approximately 30%
of all adult AML cases. This subtype of AML has a five-year overall
survival rate of approximately 50%. Similar to KMT2A- rearranged
acute leukemia, NPM1-mutant AML is highly dependent on the
expression of specific developmental genes shown to be negatively
impacted by inhibitors of the menin-KMT2A interaction. NPM1-mutant
AML is routinely diagnosed through currently available screening
techniques. There are currently no approved therapies indicated for
NPM1-mutant AML.
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 inhibitor of the menin–KMT2A binding
interaction, and axatilimab, a monoclonal antibody that blocks the
colony stimulating factor 1 (CSF-1) receptor. For more information,
please visit www.syndax.com or follow the Company
on 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 "may," "will," "expect," "plan," "anticipate,"
"estimate," "intend," "could," "conviction," "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 potential
submission of an NDA by year-end, 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 (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
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