LEXINGTON, Mass., Feb. 9, 2021 /PRNewswire/ -- Curis, Inc. (NASDAQ:
CRIS), a biotechnology company focused on the development of
innovative therapeutics for the treatment of cancer, today
announced that the first patient has been dosed in its Phase 1
trial evaluating CA-4948, a novel, small molecule IRAK4 kinase
inhibitor, in combination with ibrutinib, a BTK inhibitor, in
patients with relapsed or refractory (R/R) hematologic
malignancies.
"In dosing the first patient in this Phase 1 study evaluating
CA-4948 and ibrutinib, we are taking a highly anticipated step
forward in bringing a potent oral therapeutic regimen to patients
with relapsed or refractory hematologic malignancies," said
James Dentzer, President and Chief
Executive Officer of Curis. "BTK inhibitors are an approved
category of therapies for patients with various lymphatic cancers
yet they only target one of the two main pathways activating NF-κB
in B-cell malignancies. CA-4948 targets the other main
NF-κB-activating pathway by shutting down signaling through the
Myddosome. We have shown highly encouraging increased
tumor-reducing activity when combining both covalent and
non-covalent BTK inhibitors with CA-4948 in preclinical
models."
Mr. Dentzer continued, "We observed single-agent activity in the
non-Hodgkin's lymphoma (NHL) monotherapy study, with the majority
of patients treated at 300mg twice daily experiencing at least some
reduction in tumor volume. We coordinated with our trial partners
to amend the protocol of our existing study to include combination
therapy starting at a previously demonstrated therapeutic dose.
This will allow us to leverage the clinical sites and staff
currently active in our monotherapy study and should save
significant time and resources as we advance through the
clinic."
"Given the profile CA-4948 has demonstrated in existing studies,
it is a promising candidate for combination with a proven BTK
inhibitor such as ibrutinib," said Dr. Erel
Joffe, M.D., Assistant Attending with the Lymphoma Service
at Memorial Sloan Ketting Cancer Center and a lead investigator on
the study. "We believe there may be important synergies given that
IRAK4 controls the critical TLR pathway that is parallel and
complementary to the BTK pathway and that both of these pathways
are primary and independent oncogenic activators of NF-κB in
lymphoma and leukemia. Effective dual targeting of both independent
pathways that drive excessive B-cell proliferation via NF-κB could
potentially provide significantly improved outcomes over either
treatment in a monotherapy setting."
About the CA-4948+ibrutinib Phase 1 Combination Study
The Phase 1 trial is a two-part, multicenter, open-label, dose
escalation and expansion study designed to evaluate the safety,
pharmacokinetics, pharmacodynamics, clinical activity, and
biomarker correlations of CA-4948 and ibrutinib patients with
relapsed or refractory hematologic malignancies. Part 1 of the
study is a dose escalation using a 3+3 design. Approximately 18
patients will be enrolled in Part 1 and will receive a starting
dose of 200mg CA-4948 BID with subsequent escalation to 300mg BID,
both of which have been observed to be safe and effective in the
NHL monotherapy study, combined with ibrutinib doses appropriate
for their respective NHL subtype. The primary endpoints of Part 1
will be safety and tolerability, maximum tolerated dose, and the
recommended Phase 2 dose. Secondary objectives will be
pharmacokinetics and preliminary efficacy. Exploratory objectives
will include biomarker correlations, such as MYD88-L265P mutations
and IRAK4 pathway and NFκB inhibition.
Part 2 of the study will enroll patients across an expansion
basket of four cohorts: marginal zone lymphoma (MZL), ABC-DLBCL,
primary central nervous system lymphoma (PCNSL), and NHL with
adaptive ibrutinib resistance. An interim futility analysis will be
conducted after approximately 15-20 patients are enrolled in each
cohort. Primary endpoints of Part 2 will be complete response or
objective response rate and duration of response compared to
historical controls. Secondary objectives will be safety and
tolerability, progression-free survival, and population PK sampling
for CA-4948. Exploratory objectives will include response
correlation with biomarkers including MYD88-L265P or other genetic
mutations, gene expressions, cell of origin, IRAK4 signaling, and
resistance.
About Curis, Inc.
Curis is a biotechnology company focused on the development of
innovative therapeutics for the treatment of cancer. In 2015, Curis
entered into a collaboration with Aurigene in the areas of
immuno-oncology and precision oncology. As part of this
collaboration, Curis has exclusive licenses to oral small molecule
antagonists of immune checkpoints including the VISTA/PDL1
antagonist CA-170, and the TIM3/PDL1 antagonist CA-327, as well as
the IRAK4 kinase inhibitor, CA-4948. CA-4948 is currently
undergoing testing in a Phase 1 in patients with non-Hodgkin's
lymphoma both as a monotherapy and in combination with BTK
inhibitor ibrutinib. Curis is also evaluating CA-4948 in a Phase 1
trial in patients with acute myeloid leukemia and myelodysplastic
syndromes. In addition, Curis is engaged in a collaboration with
ImmuNext for development of CI-8993, a monoclonal
anti-VISTA antibody, which is currently undergoing testing in
a Phase 1a/1b trial in patients with solid tumors. Curis is
also party to a collaboration with Genentech, a member of the Roche
Group, under which Genentech and Roche are commercializing
Erivedge® for the treatment of advanced basal cell
carcinoma. For more information, visit Curis' website at
www.curis.com.
Forward-Looking Statements:
This press release contains forward-looking statements within
the meaning of the U.S. Private Securities Litigation Reform Act of
1995, including, without limitation, statements regarding any
expectations of the potential for the Company's proprietary drug
candidate CA-4948, including the potential developments and
benefits of CA-4948 in combination with BTK inhibitors such as
ibrutinib, statements with respect to the timing of the
Company's studies, including enrollment and reporting of data, and
the Company's ability to advance and broaden its clinical programs.
Forward-looking statements may contain the words "believes,"
"expects," "anticipates," "plans," "intends," "seeks," "estimates,"
"assumes," "will," "may," "could" or similar expressions. These
forward-looking statements are not guarantees of future performance
and involve risks, uncertainties, assumptions and other important
factors that may cause actual results to be materially different
from those indicated by such forward-looking statements. For
example, Curis may experience adverse results, delays and/or
failures in its drug development programs and may not be able to
successfully advance the development of its drug candidates in the
time frames it projects, if at all. Curis's drug candidates may
cause unexpected toxicities, fail to demonstrate sufficient safety
and efficacy in clinical studies and/or may never achieve the
requisite regulatory approvals needed for commercialization.
Favorable results seen in preclinical studies and early clinical
trials of Curis's drug candidates may not be replicated in later
trials. There can be no guarantee that the collaboration agreements
with Aurigene and ImmuNext will continue for their full terms, that
Curis or its collaborators will each maintain the financial and
other resources necessary to continue financing its portion of the
research, development and commercialization costs, or that the
parties will successfully discover, develop or commercialize drug
candidates under the collaboration. Regulatory authorities may
determine to delay or restrict Genentech's and/or Roche's ability
to continue to develop or commercialize Erivedge in BCC. Erivedge
may not demonstrate sufficient or any activity to merit its further
development in disease indications other than BCC. Competing drugs
may be developed that are superior to Erivedge. In connection with
its agreement with Oberland Capital, Curis faces risks relating to
the transfer and encumbrance of certain royalty and royalty-related
payments on commercial sales of Erivedge, including the risk that,
in the event of a default by Curis or its wholly-owned subsidiary,
Curis could lose all retained rights to future royalty and
royalty-related payments, Curis could be required to repurchase
such future royalty and royalty-related payments at a price that is
a multiple of the payments it has received, and its ability to
enter into future arrangements may be inhibited, all of which could
have a material adverse effect on its business, financial condition
and stock price. Curis will require substantial additional capital
to fund its business. If it is not able to obtain sufficient
funding, it will be forced to delay, reduce in scope or eliminate
some of its research and development programs, including related
clinical trials and operating expenses, potentially delaying the
time to market for, or preventing the marketing of, any of its
product candidates, which could adversely affect its business
prospects and its ability to continue operations, and would have a
negative impact on its financial condition and its ability to
pursue its business strategies. Curis faces substantial
competition. Curis also faces risks relating to potential adverse
decisions made by the FDA and other regulatory authorities,
investigational review boards, and publication review bodies. Curis
may not obtain or maintain necessary patent protection and could
become involved in expensive and time-consuming patent litigation
and interference proceedings. Unstable market and economic
conditions, natural disasters, public health crises, political
crises and other events outside of Curis's control could
significantly disrupt its operations or the operations of third
parties on which Curis depends, and could adversely impact Curis's
operating results and its ability to raise capital. For example,
the COVID-19 pandemic may result in closures of third-party
facilities, impact enrollment in clinical trials or impact sales of
Erivedge by Genentech and/or Roche. The extent to which
the COVID-19 pandemic may impact Curis's business or operating
results is uncertain. Other important factors that may cause or
contribute to actual results being materially different from
those indicated by forward-looking statements include the factors
set forth under the caption "Risk Factors" in our most recent Form
10-K and Form 10-Q and the factors that are discussed in other
filings that we periodically make with the Securities and Exchange
Commission ("SEC"). In addition, any forward-looking statements
represent the views of Curis only as of today and should not be
relied upon as representing Curis's views as of any subsequent
date. Curis disclaims any intention or obligation to update any of
the forward-looking statements after the date of this press release
whether as a result of new information, future events or otherwise,
except as may be required by law.
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SOURCE Curis, Inc.