Oncternal Therapeutics Announces Opening of Randomized Phase 2 Study of Cirmtuzumab in Combination with Ibrutinib
August 06 2019 - 8:00AM
Oncternal Therapeutics, Inc., (Nasdaq: ONCT) a clinical-stage
biotechnology company developing potential first-in-class product
candidates for cancers with critical unmet medical need, today
announced that it has opened for enrollment its randomized Phase 2
study of cirmtuzumab, a ROR1-targeted monoclonal antibody, combined
with ibrutinib in patients with chronic lymphocytic leukemia (CLL).
The decision to open Phase 2 of the company’s ongoing Phase 1/2
CIRLL (Cirmtuzumab and Ibrutinib targeting ROR1 for Leukemia and
Lymphoma) clinical trial was triggered by favorable outcomes from
the Part 1 dose-finding and Part 2 dose-confirming cohorts of the
clinical trial, including an observed interim objective response
rate (ORR) of 100% for the first 9 CLL patients with evaluable data
receiving the recommended dosing regimen who have completed 12
weeks of cirmtuzumab plus ibrutinib treatment in Part 2, and a
well-tolerated safety profile consistent with that seen with
ibrutinib treatment alone.
In June, the company presented data at the American Society of
Clinical Oncology (ASCO) annual meeting, reporting that results
from the first 12 patients with CLL treated in Part 1 of the Phase
1 portion of the study showed an observed interim objective
response rate (ORR) of 91.7% for the combination of cirmtuzumab
plus ibrutinib, including three patients with clinical or confirmed
complete responses, and a well-tolerated safety profile consistent
with that seen for ibrutinib treatment alone.
Included in the results presented at ASCO were preliminary
results from six patients with mantle cell lymphoma (MCL), who were
treated in a separate cohort of the CIRLL study. Data from this
cohort will be presented at a future medical conference. One
patient with MCL who had relapsed following an allogeneic stem cell
transplant experienced a confirmed complete response (CR) after 3
months of cirmtuzumab plus ibrutinib treatment, including complete
resolution of a large mediastinal mass. This CR appears to be
durable, and has been confirmed after 6, 9 and 11 months of
cirmtuzumab plus ibrutinib treatment.
The CIRLL clinical trial is supported by a grant from the
California Institute for Regenerative Medicine (CIRM) and is being
conducted in collaboration with the University of California at San
Diego (UC San Diego).
“We are very pleased to be opening the randomized Phase 2
portion of the CIRLL study for patients with CLL and continue to be
encouraged by the interim results from the study for both patients
with CLL and patients with mantle cell lymphoma,” said James
Breitmeyer, M.D., Ph.D., Oncternal’s President and CEO.
About the StudyThe CIRLL Study (CIRM-0001) is a
Phase 1/2 clinical trial evaluating cirmtuzumab in combination with
ibrutinib in patients with CLL or MCL. Part 1 of the study was a
Phase 1 dose-finding portion designed to determine the Phase 2
dose, or recommended dosing regimen (RDR). Part 2 was a Phase 1b
expansion cohort to confirm the RDR. Interim analyses were
specified for Part 1 and Part 2. Part 3 of the study, which is now
open for enrollment, is a Phase 2 study in which approximately 90
patients with CLL will be randomized to receive either ibrutinib
alone or ibrutinib plus cirmtuzumab, with a primary endpoint of
complete response rate. An interim assessment of the first 12
patients with CLL enrolled in Part 1 of the study was presented as
a poster at the 2019 ASCO Annual Meeting. Additional information
about the CIRM-0001 study and other clinical studies of cirmtuzumab
may be accessed at
ClinicalTrials.gov. About
Cirmtuzumab Cirmtuzumab is an investigational,
potentially first-in-class monoclonal antibody targeting ROR1, or
Receptor tyrosine kinase-like Orphan Receptor 1. Cirmtuzumab is
currently in a Phase 1/2 clinical trial in combination with
ibrutinib for the treatment of CLL and MCL, in a collaboration with
the University of California San Diego School of Medicine and the
California Institute for Regenerative Medicine. In addition, an
investigator-initiated Phase 1 clinical trial of cirmtuzumab in
combination with paclitaxel for women with metastatic breast cancer
is being conducted at the UC San Diego School of Medicine. CIRM has
also provided funding to support development programs for
cirmtuzumab and a CAR-T product candidate that targets ROR1, which
is currently in preclinical development as a potential treatment
for hematologic cancers and solid
tumors.
When expressed by hematologic malignancies such as CLL and MCL,
ROR1 acts as a receptor for the tumor growth factor Wnt5a.
Researchers at the UC San Diego School of Medicine discovered that
targeting a critical epitope on ROR1 was key to inhibiting Wnt5a
activation, specifically targeting ROR1 expressing tumors, and this
finding led to the discovery of the potent and highly selective
antitumor activity of cirmtuzumab observed in preclinical studies.
Oncternal believes ROR1 is an attractive target for cancer therapy
because it is an oncofetal antigen – a protein not normally
expressed in adults, but which confers a survival and fitness
advantage when reactivated and expressed by tumor cells.
Preclinical data indicate that when cirmtuzumab binds to ROR1, it
blocks Wnt5a signaling, induces differentiation of the tumor cells,
and inhibits tumor cell proliferation, migration and survival.
Cirmtuzumab is in clinical development and has not been approved by
the U.S. Food and Drug Administration for any
indication.
About Oncternal Therapeutics Oncternal
Therapeutics is a clinical-stage biopharmaceutical company focused
on developing a diverse pipeline of product candidates for the
treatment of cancers with critical unmet medical need. Oncternal
focuses drug development on promising yet untapped biological
pathways implicated in cancer generation or progression. The
pipeline includes cirmtuzumab, a monoclonal antibody designed
to inhibit the ROR1 receptor that is being evaluated in a Phase 1/2
clinical trial in combination with ibrutinib for the treatment of
CLL and MCL, and TK-216, a small-molecule compound that is
designed to inhibit E26 transformation specific (ETS) family
oncoproteins, which is being evaluated in a Phase 1 clinical trial
alone and in combination with vincristine as a treatment for Ewing
sarcoma, a rare pediatric cancer. In addition, Oncternal has
a CAR-T product candidate that targets ROR1, which is
currently in preclinical development as a potential treatment for
hematologic cancers and solid tumors. More information is available
at www.oncternal.com.
Forward-Looking Information Oncternal cautions
you that statements included in this press release that are not a
description of historical facts are forward-looking statements. In
some cases, you can identify forward-looking statements by terms
such as “may,” “will,” “should,” “expect,” “plan,” “anticipate,”
“could,” “intend,” “target,” “project,” “contemplates,” “believes,”
“estimates,” “predicts,” “potential” or “continue” or the negatives
of these terms or other similar expressions. These statements are
based on the Company’s current beliefs and expectations.
Forward looking statements include statements regarding:
Oncternal’s belief that favorable outcomes from the ongoing Phase 1
portion of the clinical trial support opening the Phase 2 portion;
and Oncternal’s plans for enrolling patients in, and presenting
data from, its clinical studies of cirmtuzumab. The inclusion of
forward-looking statements should not be regarded as a
representation by Oncternal that any of its plans will be
achieved. Actual results may differ from those set forth in this
release due to the risks and uncertainties inherent in Oncternal’s
business, including, without limitation: uncertainties associated
with the clinical development and process for obtaining regulatory
approval of cirmtuzumab and Oncternal’s other product candidates,
including potential delays in the commencement, enrollment and
completion of clinical trials; the Company’s dependence on the
success of cirmtuzumab and its other product development programs;
the risk that interim results of a clinical trial do not
necessarily predict final results and that one or more of the
clinical outcomes may materially change as patient enrollment
continues, following more comprehensive reviews of the data, and as
more patient data become available; the risk that unforeseen
adverse reactions or side effects may occur in the course of
developing and testing product candidates such as cirmtuzumab and
Oncternal’s other product candidates; the Company’s limited
operating history and that fact that it has incurred significant
losses, and expects to continue to incur significant losses for the
foreseeable future; risks related to the inability of Oncternal to
obtain sufficient additional capital to continue to advance the
development of cirmtuzumab and its other product candidates; and
other risks described in the Company’s prior press releases as well
as in public periodic filings with the U.S. Securities &
Exchange Commission. All forward-looking statements in this press
release are current only as of the date hereof and, except as
required by applicable law, Oncternal undertakes no obligation to
revise or update any forward-looking statement, or to make any
other forward-looking statements, whether as a result of new
information, future events or otherwise. All forward-looking
statements are qualified in their entirety by this cautionary
statement. This caution is made under the safe harbor provisions of
the Private Securities Litigation Reform Act of 1995.
Oncternal Contacts:
Investors
Richard Vincent
858-434-1113
rvincent@oncternal.com
Media
Jason Spark
619-849-6005
jason@canalecomm.com
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