– Consistent safety and efficacy profiles
across adult and pediatric populations –
– Majority of pediatric patients who
achieved an overall response proceeded to transplant; patients
receiving post-transplant revumenib maintenance remained in
remission as of data cutoff date –
– No treatment-related discontinuations or
dose reductions –
WALTHAM,
Mass., April 8, 2024 /PRNewswire/ -- Syndax
Pharmaceuticals (NASDAQ: SNDX), a clinical stage biopharmaceutical
company developing an innovative pipeline of cancer therapies,
today announced the presentation of positive data from the pivotal
AUGMENT-101 trial in pediatric patients with relapsed/refractory
(R/R) KMT2A-rearranged (KMT2Ar) acute myeloid leukemia (AML) and
acute lymphoid leukemia (ALL) treated with revumenib, a
first-in-class menin inhibitor. The pediatric data was featured in
a Plenary Session titled "Pivotal Phase 2 Results of AUGMENT-101
for Revumenib in KMT2Ar Acute Leukemia: Pediatric Experience" at
the 2024 American Society of Pediatric Hematology/Oncology (ASPHO)
Conference held April 3 – 6, 2024 in
Seattle,
Washington.
"We are pleased to present positive results from pediatric
patients treated with revumenib in the AUGMENT-101 pivotal trial
demonstrating impressive activity and consistency with the adult
population," said Neil Gallagher, M.D., Ph.D., President, Head
of Research and Development at Syndax. "As the only menin inhibitor
with a formulation designed for the pediatric setting, we have an
ongoing commitment to bringing this first- and best-in-class
therapeutic agent to this important patient population in need of
effective treatments."
The presented data include efficacy and safety findings for
pediatric patients with R/R KMT2Ar acute leukemia from the pivotal
Phase 2 portion of the AUGMENT-101 study. Of the 57 patients
enrolled in AUGMENT-101 with central confirmation of their KMT2Ar
status and sufficient follow-up to be included in the
efficacy-evaluable population, 13 (23%) were less than 18 years old
with a median age of 5 years. The pediatric patients were heavily
pretreated with a median of 4 prior lines of therapy including 8
(62%) that received prior venetoclax, 2 (15%) that received CAR-T
and 6 (46%) that received prior hematopoietic stem cell transplant
(HSCT).
In this population, the complete remission (CR) or CR with
partial hematological recovery (CRh) rate was 23% (3/13; 95% CI:
5.0, 53.8), with a median time to CR or CRh of 2.3 months (95% CI:
1.0, 3.9). The overall response rate1 was 46% (6/13),
and the composite response rate2 (CRc) was 39% (5/13).
Sixty percent (3/5) of CRc patients achieved minimal residual
disease negative status. The median overall survival was 6.9 months
(95% CI, 2.3–not reached). Four (67%) of the 6 patients who
achieved an overall response underwent HSCT, two of whom did not
achieve a CR or CRh prior to transplant. Half (2/4) of the patients
who underwent HSCT received post-transplant maintenance with
revumenib and had been in remission for 6 and 9 months at the time
of the July 24, 2023 data cutoff.
Revumenib was well-tolerated, and the safety profile was
consistent with the Company's previously reported data. In
the safety-evaluable patient population, Grade 3 or greater
treatment-related adverse events that occurred in greater than 10%
of patients included febrile neutropenia (13%; 3/23) and decreased
neutrophil count (13%; 3/23). Grade 3 or greater
differentiation syndrome was observed in 9% (2/23) of patients and
Grade 3 QTc prolongation was observed in 4% (1/23) of patients.
No treatment-related discontinuations or dose reductions due
to adverse events occurred in the trial.
A copy of the presentation is 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, also known as mixed lineage leukemia
rearranged or MLLr, acute leukemias including ALL and AML, and
NPM1-mutant AML. Positive topline results from the Phase 2
AUGMENT-101 trial in R/R KMT2Ar acute leukemia showing the trial
met its primary endpoint with a CR/CRh rate of 23% (13/57; 95%
confidence interval [CI]: [12.7, 35.8, one-sided p-value =
0.0036]) were presented at the 65th American
Society of Hematology Annual Meeting. 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. The New Drug Application (NDA) for
revumenib for the treatment of adult and pediatric R/R KMT2Ar acute
leukemia was granted Priority Review by the FDA with a Prescription
Drug User Fee Act target action date of September 26, 2024,
under the Real-Time Oncology Review Program.
About AUGMENT-101
AUGMENT-101 is a Phase 1/2 open-label trial designed to evaluate
the safety, tolerability, pharmacokinetics, and efficacy of orally
administered revumenib. The Phase 1 dose escalation portion of
AUGMENT-101 included two cohorts based on concomitant treatment
with a strong CYP3A4 inhibitor. Arm A enrolled patients not
receiving a strong CYP3A4 inhibitor, while Arm B enrolled patients
receiving a strong CYP3A4 inhibitor. The Phase 2 pivotal portion of
AUGMENT-101 has enrolled R/R patients across the following trial
populations: patients with mNPM1 AML, patients with KMT2Ar AML, and
patients with KMT2Ar ALL. The primary endpoint for each
of the cohorts is efficacy as measured by complete remission rate
(CR + CRh) per protocol, with secondary endpoints including
duration of response and overall survival (OS). Positive data
from the pivotal AUGMENT-101 trial of revumenib in adult and
pediatric patients with KMT2Ar AML and ALL served as the basis for
the NDA submission that is currently under review by the FDA.
Enrollment has been completed in the AUGMENT-101 pivotal trial
cohort of patients with R/R mNPM1 AML and topline data is expected
in the fourth quarter of 2024.
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, and
the median OS is less than three months. There are currently no
approved therapies indicated for KMT2A-rearranged acute
leukemia.
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 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
1 Overall response rate includes CR, CRh, CRp,
CRi, MLFS, and PR
2 Composite response rate includes CR, CRh, CRp,
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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SOURCE Syndax Pharmaceuticals, Inc.
