– Two CRs, four PRs (46% ORR) observed in
advanced AITL patients in Phase 2 trial of tipifarnib in PTCL –
Kura Oncology, Inc. (Nasdaq: KURA), a clinical-stage
biopharmaceutical company focused on the development of precision
medicines for oncology, reported preliminary data in
angioimmunoblastic T-cell lymphoma (AITL) and CXCL12+ peripheral
T-cell lymphoma (PTCL), the two expansion cohorts in its Phase 2
clinical trial of its lead drug candidate tipifarnib in patients
with relapsed or refractory PTCL.
The data, presented today at the American Society of Hematology
(ASH) Annual Meeting in San Diego, showed encouraging activity with
tipifarnib in late-stage PTCL patients, including a significant
association between CXCL12 expression and clinical benefit, and
proof of concept in AITL, an aggressive form of T-cell lymphoma
often characterized by high levels of CXCL12 expression. A copy of
the poster is available on the Company's website at
www.kuraoncology.com.
“The mechanism of action of farnesyl transferase inhibitors has
remained elusive for several decades,” said Antonio Gualberto,
M.D., Ph.D., Head of Development and Chief Medical Officer of Kura
Oncology. “Our initial data in HRAS mutant head and neck cancer
provided strong evidence of activity in tumors driven by this
oncogene. However, many other tumors such as T- and B-cell
lymphomas, myeloid leukemias, pancreatic or breast cancers, in
which anecdotal evidence of tipifarnib activity has been reported,
do not usually carry HRAS mutations. We believe the preliminary
results reported at ASH validate our observation that the CXCL12
pathway is a therapeutic target of tipifarnib and provide a
potential path to expand the development of tipifarnib well beyond
HRAS mutant solid tumors by using CXCL12-related biomarkers to
enrich for patients most likely to benefit from treatment. We will
continue our efforts to identify these patient subsets and to bring
this important drug candidate to patients in need.”
As of November 21, 2018, a total of 39 patients were enrolled in
the ongoing Phase 2 trial, including 19 patients with AITL (16
patients in the AITL extension cohort and 3 patients in the
previous portion of the study). Six of the 16 AITL patients were
not evaluable as of the data cutoff date, including two who were
pending initial efficacy assessments. Of the 13 evaluable AITL
patients, two achieved a complete response (CR) and four achieved a
partial response (PR), for an objective response rate (ORR) of 46%
(six of 13). According to the study protocol, the AITL cohort is
considered positive when four or more responses are observed.
The study also identified a particularly responsive subset
within AITL and non-AITL patients. Specifically, patients with a
high ratio of expression of CXCL12 to its receptor CXCR4
experienced a 50% ORR (five of 10) and a 90% clinical benefit rate
(nine of 10 with either complete response, partial response or
stable disease) with tipifarnib. Patients in this Phase 2 trial had
a median of three prior lines of therapy (range 1-7). The high
CXCL12/CXCR4 expression ratio had 90% sensitivity and 93%
specificity to identify PTCL patients likely to benefit from
tipifarnib.
In addition to the Phase 2 clinical data, the results from two
ancillary, non-clinical studies were also reported at ASH. In the
first, the expression of CXCL12 and CXCR4 was investigated using
tumor bank samples of PTCL patients treated with standard-of-care
agents. Worse prognosis was observed in PTCL patients with high
CXCL12/CXCR4 expression ratio, indicating that CXCL12 is a negative
prognostic factor for standard PTCL therapy. In the second study,
the effect of the incubation of stroma cells with tipifarnib on
CXCL12 secretion was investigated in a mouse model of bone marrow
culture. Tipifarnib reduced secretion of the CXCL12 chemokine from
the stromal cells, providing a potential mechanism of action for
the observed clinical activity.
“To our knowledge, these results position tipifarnib as the
first CXCL12 inhibitor with reported proof-of-concept data, marking
a significant advancement in our development strategy,” said Troy
Wilson, Ph.D., President and CEO of Kura Oncology. “Our data
suggest that as many as 40% of PTCL patients express high CXCL12.
In addition, the discovery of CXCL12-related biomarkers offers the
potential to increase the opportunity for tipifarnib into other
hematological and solid tumor indications. We intend to explore
those indications while continuing to gather additional data from
our ongoing Phase 2 study and expect to provide an update at a
medical meeting next year.”
The Phase 2 study was designed to investigate the anti-tumor
activity of tipifarnib in patients with relapsed or refractory
PTCL. After preliminary data suggested that CXCL12 expression was
associated with tipifarnib’s clinical activity, two expansion
cohorts were added to enroll patients with tumors expected to
overexpress CXCL12: AITL tumors, and those non-AITL tumors that
lack a single nucleotide variation in the 3’-untranslated region
(3'-UTR) of the CXCL12 gene (CXCL12+ PTCL). CXCL12 is a
stroma-derived chemokine that promotes the progression of lymphoma
and other hematological and solid tumors carrying the CXCR4
receptor, and our previous results had suggested an association
between CXCL12 expression and the most common form of the 3’-UTR
CXCL12 variant. In the expansion cohorts, both the presence or
absence of this variant and the expression levels of CXCL12 and
CXCR4 were assessed.
In the expansion cohorts in the Phase 2 trial tipifarnib was
dosed at 300 mg twice daily on days 1-21 of a 28-day cycle. The
reported data indicated that tipifarnib was generally
well-tolerated, with adverse events consistent with its known
safety profile. The most common treatment-related adverse events
(grade ≥ 3) were hematology-related, including neutropenia,
thrombocytopenia, leukopenia, febrile neutropenia and anemia.
Last week, the U.S. Patent and Trademark Office (USPTO) issued a
new patent for tipifarnib as a method of treating patients with
AITL. In May 2018, the USPTO issued a patent for tipifarnib as a
method of treating patients with certain CXCL12-expressing cancers,
including PTCL. Both patents expand protection for tipifarnib,
providing exclusivity in the U.S. to 2037.
Webcast Information
Kura’s management will host a webcast at 11:30 p.m. ET / 8:30
p.m. PT today, December 2, 2018, following the conclusion of the
poster presentation at the ASH 2018 Annual Meeting. The live audio
webcast and slides of the presentation will be available from the
Investors and Media section of the company website at
www.kuraoncology.com, and will be archived there for 30 days.
About Tipifarnib
Kura Oncology’s lead drug candidate, tipifarnib, is a potent and
highly selective inhibitor of farnesylation, a key cell signaling
process implicated in cancer initiation and development. Tipifarnib
was previously studied in more than 5,000 cancer patients and
showed compelling and durable anti-cancer activity in certain
patient subsets, however no molecular mechanism of action had
previously been determined that could explain its activity across a
range of diverse clinical indications, including squamous tumors
that carry mutant HRAS, as well as in lymphoid, myeloid and solid
tumors that do not carry HRAS mutations. Leveraging advances in
next-generation sequencing as well as emerging information about
cancer genetics and tumor biology, Kura is seeking to identify
those patients most likely to benefit from tipifarnib. In November
2018, Kura initiated its first global, registration-directed trial
of tipifarnib in patients with recurrent or metastatic HRAS mutant
HNSCC.
About Kura Oncology
Kura Oncology is a clinical-stage biopharmaceutical company
committed to realizing the promise of precision medicines for the
treatment of cancer. The Company’s pipeline consists of small
molecule drug candidates that target cancer signaling pathways
where there is a strong scientific and clinical rationale to
improve outcomes by identifying those patients most likely to
benefit from treatment. Kura’s lead drug candidate is tipifarnib, a
farnesyl transferase inhibitor, for which the Company has initiated
a registration-directed trial of tipifarnib in recurrent or
metastatic patients with HRAS mutant HNSCC. In addition, tipifarnib
is being evaluated in multiple other Phase 2 clinical trials in
solid tumor and hematologic indications. Kura’s pipeline also
includes KO-947, an ERK inhibitor, currently in a Phase 1
dose-escalation trial, and KO-539, a menin-MLL inhibitor, currently
in IND-enabling studies. For additional information about Kura
Oncology, please visit the Company’s website at
www.kuraoncology.com.
Forward-Looking Statements
This news release contains certain forward-looking statements
that involve risks and uncertainties that could cause actual
results to be materially different from historical results or from
any future results expressed or implied by such forward-looking
statements. Such forward-looking statements include statements
regarding, among other things, the efficacy, safety and therapeutic
potential of tipifarnib and the Company’s other product candidates,
the conduct, results and timing of Kura Oncology’s clinical trials,
including the Phase 2 clinical trial of tipifarnib in patients with
PTCL, plans regarding future clinical trials and development and
commercial activities, the regulatory approval path for tipifarnib
and expectations regarding intellectual property and biomarkers
related to Kura Oncology’s product candidates. Factors that may
cause actual results to differ materially include the risk that
compounds that appeared promising in early research or clinical
trials do not demonstrate safety and/or efficacy in later
preclinical studies or clinical trials, the risk that Kura Oncology
may not obtain approval to market its product candidates,
uncertainties associated with performing clinical trials,
regulatory filings and applications, risks associated with reliance
on third parties to successfully conduct clinical trials, the risks
associated with reliance on outside financing to meet capital
requirements, and other risks associated with the process of
discovering, developing and commercializing drugs that are safe and
effective for use as human therapeutics, and in the endeavor of
building a business around such drugs. You are urged to consider
statements that include the words “may,” “will,” “would,” “could,”
“should,” “believes,” “estimates,” “projects,” “promise,”
“potential,” “expects,” “plans,” “anticipated,” “intends,”
“continues,” “designed,” “goal,” or the negative of those words or
other comparable words to be uncertain and forward-looking. For a
further list and description of the risks and uncertainties the
Company faces, please refer to the Company’s periodic and other
filings with the Securities and Exchange Commission, which are
available at www.sec.gov. Such forward-looking statements are
current only as of the date they are made, and Kura Oncology
assumes no obligation to update any forward-looking statements,
whether as a result of new information, future events or
otherwise.
Contacts
Company:Pete De SpainVice President, Investor Relations
&Corporate Communications(858)
500-8803pete@kuraoncology.com
Investors:Robert H. UhlManaging DirectorWestwicke Partners,
LLC(858) 356-5932robert.uhl@westwicke.com
Media:Jason SparkManaging DirectorCanale Communications(619)
849-6005jason@canalecomm.com
Kura Oncology (NASDAQ:KURA)
Historical Stock Chart
From Mar 2024 to Apr 2024
Kura Oncology (NASDAQ:KURA)
Historical Stock Chart
From Apr 2023 to Apr 2024