- Preliminary exploratory efficacy results from phase 1
study show an overall response rate of 58.8 percent with single
agent DS-3201, an investigational and potential first-in-class
EZH1/2 dual inhibitor, in patients with relapsed or refractory
non-Hodgkin lymphomas
- In subgroup analyses, an overall response rate of 45.5
percent with DS-3201 was observed in patients with B-cell lymphomas
and 83.3 percent in patients with T-cell lymphomas
- Separate study of DS-3201 also underway in U.S. in
patients with acute myeloid leukemia and acute lymphocytic
leukemia, underscoring Daiichi Sankyo Cancer Enterprise commitment
to advancing science for blood cancers
TOKYO and BASKING RIDGE,
New Jersey and MUNICH, Dec. 11,
2017 /PRNewswire/ -- Daiichi Sankyo Company, Limited
(hereafter, Daiichi Sankyo) today announced that preliminary safety
and efficacy data from a phase 1 study of DS-3201, an
investigational and potential first-in-class EZH1/2 dual inhibitor,
in patients with relapsed or refractory non-Hodgkin lymphomas
(NHLs) were presented during a poster session at the
59th Annual Meeting of the American Society of
Hematology in Atlanta,
Georgia.
Preliminary exploratory efficacy results from an ongoing phase 1
dose escalation study showed that an overall response rate of 58.8
percent (10 of 17 patients) was observed with single agent DS-3201
in 17 evaluable patients with NHLs, including B-cell and T-cell
lymphomas, who were relapsed from or refractory to standard
treatment or for whom no standard treatment was available. Among
the 10 patients with response, there were one complete remission
and nine partial remissions. Additionally, four patients
experienced stable disease and three patients experienced
progressive disease.
An overall response rate of 45.5 percent (5 of 11 patients) was
observed with DS-3201 in 11 evaluable patients with B-cell
lymphomas, including follicular lymphoma (5 patients), diffuse
large B-cell lymphoma (3 patients), extranodal marginal zone
lymphoma of mucosa-associated lymphoid tissue (2 patients) and
lymphoplasmacytic lymphoma (1 patient). An overall response rate of
83.3 percent (5 of 6 patients) was observed with DS-3201 in six
evaluable patients with T-cell lymphomas, including peripheral
T-cell lymphoma not otherwise specified (2 patients),
angioimmunoblastic T-cell lymphoma (2 patients) and adult T-cell
leukemia-lymphoma (2 patients).
"Based on these preliminary safety and efficacy data on DS-3201
in a clinical setting, further evaluation of DS-3201 is warranted,"
said Dai Maruyama, MD, PhD,
Department of Hematology, National Cancer Center Hospital,
Tokyo, Japan. "As the first dual
inhibitor of EZH1 and EZH2 in clinical development, DS-3201 may
represent a new epigenetic approach to treating blood cancers. We
look forward to reviewing additional data as it becomes available
to evaluate the potential of this approach."
Following observation of dose-limiting toxicities (DLTs) in
three of 18 evaluable patients, dose expansion is ongoing to
determine a conclusive recommended phase 2 dose. Four DLTs were
observed in three patients who received either the 200 mg or 300 mg
dose: there were three cases of temporary grade 4 platelet count
decreases (one patient in the 200 mg cohort and two patients in the
300 mg cohort) and one case of grade 3 anemia requiring transfusion
in a patient in the 300 mg cohort. Preliminary safety data from 18
evaluable patients in the study also were reported. The most common
treatment emergent hematologic adverse events of any grade seen in
all patients included decreased platelet count (77.8 percent),
anemia (55.6 percent), decreased lymphocyte count (50.0 percent)
and decreased neutrophil count (44.4 percent). The most common
treatment emergent non-hematologic adverse events were dysgeusia
(50.0 percent), alopecia (33.3 percent), diarrhea (22.2 percent),
decreased appetite (22.2 percent), nasopharyngitis (22.2 percent),
alanine aminotransferase increased (22.2 percent), rash (16.7
percent), aspartate aminotransferase increased (16.7 percent) and
dry skin (16.7 percent). One serious adverse event of grade 3
pneumocystis jirovecii pneumonia (PJP) led to discontinuation from
the study. There was one additional non-serious case of PJP
observed, leading to the institution of prophylactic treatment for
all subsequent patients enrolled into the study.
DS-3201 targets epigenetic regulation by inhibiting both the
EZH1 (enhancer of zeste homolog 1) and EZH2 (enhancer of zeste
homolog 2) enzymes, which may reactivate various genes that have
been silenced by the protein H3K27me3.1 Reactivation of
the silenced genes has been shown to result in decreased
proliferation of EZH2-expressing cancer cells. Preclinical research
has shown that DS-3201 suppressed trimethylation of H3K27 in cells
(IC50: 0.55 nM) more potently than EZH2 selective
inhibitors.1
"Targeting epigenetic regulation is an approach to treating
cancer that aims to reverse aberrant epigenetic changes that
contribute to cancer cell growth and to maintain normal gene
expression. The dual inhibition of EZH1/2 is theoretically able to
provide a different spectrum of activity compared to EZH2-specific
inhibitors already in the clinic. Our phase 1 program is designed
to address the question of the potential benefit for this dual mode
of action," said Antoine Yver, MD,
MSc, Executive Vice President and Global Head, Oncology Research
and Development, Daiichi Sankyo. "In addition to the phase 1 study
in non-Hodgkin lymphomas, we also are evaluating targeting
epigenetic regulation with DS-3201 in patients with acute myeloid
leukemia and acute lymphocytic leukemia."
About Non-Hodgkin Lymphoma
Non-Hodgkin lymphoma (NHL)
is a form of cancer that originates in lymphocytes, a type of white
blood cell.2 The two main types of NHL are B-cell
lymphomas and T-cell lymphomas, which are classified into subtypes
based on the origin and stage of the cancer.2 There were
an estimated 386,000 new cases and about 200,000 deaths globally
from NHL in 2012.3 In Japan, there were nearly 21,000 new cases of
NHL in 2012, accounting for around five percent of cases
worldwide.3 While recent treatment advances have led to
improved outcomes for patients with certain types of NHL, patients
with aggressive NHL subtypes or relapsed or refractory disease
still face a poor prognosis.2,4
About the DS-3201 Phase 1 Study
A multicenter,
non-randomized, open-label phase 1 dose escalation trial in
Japan is enrolling adult patients
with non-Hodgkin lymphomas (NHL) who have relapsed from or are
refractory to standard treatment or for whom no standard treatment
is available. The primary objectives are to evaluate the safety and
pharmacokinetics of multiple-dose monotherapy of DS-3201 and to
determine the recommended phase 2 dose. Secondary objectives are to
determine the maximum tolerated dose of DS-3201 and to conduct
exploratory evaluations of DS-3201-related biomarkers and the
efficacy of DS-3201. For more information about the clinical trial,
visit ClinicalTrials.gov.
About DS-3201
Part of the AML Franchise of the
Daiichi Sankyo Cancer Enterprise, DS-3201 is an investigational and
potential first-in-class EZH1/2 dual inhibitor in phase 1 clinical
development for hematologic cancers including acute myeloid
leukemia (AML), acute lymphocytic leukemia (ALL) and non-Hodgkin
lymphoma (NHL). DS-3201 is an investigational agent that has not
been approved by the FDA or any other regulatory agency worldwide
as a treatment for any indication. Safety and efficacy have not
been established.
About Daiichi Sankyo Cancer Enterprise
The vision of
Daiichi Sankyo Cancer Enterprise is to leverage our world-class,
innovative science and push beyond traditional thinking in order to
create meaningful treatments for patients with cancer. We are
dedicated to transforming science into value for patients, and this
sense of obligation informs everything we do. Anchored by our
Antibody Drug Conjugate (ADC) and Acute Myeloid Leukemia (AML)
Franchises, our cancer pipeline includes more than 20 small
molecules, monoclonal antibodies and ADCs stemming from our
powerful research engines: our two laboratories for
biologic/immuno-oncology and small molecules in Japan, and Plexxikon Inc., our small molecule
structure-guided R&D center in Berkeley, CA. For more information, please
visit: www.DSCancerEnterprise.com.
About Daiichi Sankyo
Daiichi Sankyo Group
is dedicated to the creation and supply of innovative
pharmaceutical products to address diversified, unmet medical needs
of patients in both mature and emerging markets. With over 100
years of scientific expertise and a presence in more than 20
countries, Daiichi Sankyo and its 15,000 employees around the world
draw upon a rich legacy of innovation and a robust pipeline of
promising new medicines to help people. In addition to a strong
portfolio of medicines for hypertension and thrombotic disorders,
under the Group's 2025 Vision to become a "Global Pharma Innovator
with Competitive Advantage in Oncology," Daiichi Sankyo research
and development is primarily focused on bringing forth novel
therapies in oncology, including immuno-oncology, with additional
focus on new horizon areas, such as pain management,
neurodegenerative diseases, heart and kidney diseases, and other
rare diseases. For more information, please visit:
www.daiichisankyo.com. Daiichi Sankyo, Inc., headquartered in
Basking Ridge, New Jersey, is a
member of the Daiichi Sankyo Group. For more information on Daiichi
Sankyo, Inc., please visit: www.dsi.com.
Contact
Jennifer
Brennan
Daiichi Sankyo, Inc.
jbrennan2@dsi.com
+1 908 992 6631(office)
+1 201 709 9309 (mobile)
References
|
1.
|
Honma D, et al. ASH
Annual Meeting. Abstract #2073. 2017.
|
2.
|
American Cancer
Society. Non-Hodgkin's Lymphoma. 2017.
|
3.
|
Ferlay J, et al.
GLOBOCAN 2012 v1.0. Cancer Incidence and Mortality Worldwide; IARC
CancerBase No. 11. 2013.
|
4.
|
Chao M. Cancer Manag
Res. 2013;5:251-269.
|