Kura Oncology, Inc. (Nasdaq: KURA), a clinical-stage
biopharmaceutical company focused on the development of precision
medicines for oncology, today announced updated interim data from
the ongoing Phase 2 clinical trial of its lead drug candidate,
tipifarnib, in patients with relapsed or refractory peripheral
T-cell lymphoma (PTCL).
The results, which will be presented during an oral session at
16:45 CET / 10:45 am ET tomorrow at the European Hematology
Association (EHA) Annual Congress in Amsterdam, demonstrate ongoing
anti-tumor activity and a manageable safety profile in advanced
patients with angioimmunoblastic T-cell lymphoma (AITL) as well as
non-AITL PTCL. A copy of the presentation is available on the
Company’s website at www.kuraoncology.com.
“With additional follow up and new patients enrolled in the
ongoing Phase 2 study, tipifarnib continues to demonstrate
encouraging clinical activity in patients with relapsed or
refractory PTCL who have experienced a median of three prior lines
of therapy,” said Francine Foss, M.D., professor of medicine at the
Yale Cancer Center, and a principal investigator in the trial.
“Given the grim prognosis for late-stage PTCL patients, these data
are exciting because they further validate tipifarnib as a targeted
therapy and the potential for CXCL12 pathway biomarkers as
effective enrichment strategies in late-stage PTCL patients with
few therapeutic options.”
The multi-center, single-arm, open-label Phase 2 trial was
designed to determine the efficacy, safety and biomarkers of
activity of tipifarnib in patients with relapsed or refractory
PTCL. Initially, patients were enrolled without selection in the
Phase 2 trial. Based upon molecular characterization of the initial
patients, the Phase 2 trial was amended to include two expansion
cohorts: 1) patients with AITL, an aggressive form of T-cell
lymphoma often characterized by high levels of CXCL12 expression
(the AITL expansion cohort), and 2) patients with PTCL who lack a
single nucleotide variation (rs2839685 A>G) in the
3’-untranslated region of the CXCL12 gene (the CXCL12 SNP+
expansion cohort).
As of the May 24, 2019 data cutoff, a total of 50
relapsed/refractory PTCL patients with a median number of three
prior regimens have been enrolled in all stages of the Phase 2
trial. Key preliminary findings include:
- The primary efficacy endpoint was achieved in each of the AITL
and CXCL12+ expansion cohorts. Sixteen patients were treated in the
AITL cohort and 15 in the CXCL12 SNP+ cohort. Among the 11
evaluable patients in the AITL extension cohort, three achieved a
complete response (CR) and two achieved a partial response (PR),
for an objective response rate (ORR) of 45% (31% ORR on a modified
intent-to-treat basis, mITT). Among the 12 evaluable patients in
the CXCL12+ expansion cohort, three achieved a CR and two achieved
a PR, for an ORR of 42% (33% ORR by mITT). Two of the five
responders in the CXCL12+ expansion cohort were AITL
patients.
- When all AITL patients (N=23) and all PTCL not otherwise
specified (PTCL-NOS) with available rs2839695 data and absence of
this 3’UTR variant (N=17) enrolled in all portions were taken into
account, ORR were 53%/39% (PPS/mITT) for AITL and 20%/18% for
CXCL12 SNP+ PTCL-NOS.
- Thirty-four patients had available gene expression data.
Patients with a high ratio of CXCL12 expression to its receptor
CXCR4 (N=17) experienced an ORR of 47% and a clinical benefit rate
of 82% (CR+PR+SD) with tipifarnib.
- Next-generation sequencing of 16 AITL patients revealed a high
rate of mutation/variation (50%) of the killer cell
immunoglobulin-like receptors, including KIR3DL2. KIR3DL2 mutation
at C336R was concurrent with Q386E and was associated with outcome
from tipifarnib therapy. Four of the eight KIR3DL2 C336R/Q386E
patients achieved a CR, two achieved a PR and two achieved stable
disease (SD) for a CR rate of 50%, an ORR of 75% and a clinical
benefit rate of 100%. Furthermore, high KIR3DL2 mutant variant
allele frequency KIR3DL2 was predictive of complete response to
tipifarnib in AITL. Tumors with KIR3DL2 mutations expressed low
levels of CXCL5 and its receptor CXCR1 and CXCR2, a potential
mechanism of resistance to tipifarnib.
- Tipifarnib was generally well-tolerated in this Phase 2 trial,
with adverse events consistent with its known safety profile. The
most frequently observed treatment-related adverse events (grade ≥
3) were hematology-related, including thrombocytopenia,
neutropenia, leukopenia, anemia, febrile neutropenia and
lymphopenia.
“We believe that these data validate our prior observations of
tipifarnib as a CXCL12 pathway inhibitor and constitute the first
clinical proof-of-concept of farnesyl transferase inhibitors in
CXCL12-driven tumors. AITL and related lymphomas encompass
approximately one-third of PTCL cases and represent a significant
unmet medical need,” said Antonio Gualberto, M.D., Ph.D., Head of
Development and Chief Medical Officer of Kura Oncology. “We are
also very encouraged by the discovery of KIR3DL2 mutations, the
characterization of mechanisms of sensitivity and resistance to
tipifarnib in lymphoma, and the development of robust molecular
tools for the selection and/or stratification of PTCL patients.
These findings are a testimony of the potential for success of our
precision medicine approaches.”
Poster Presentation Explores CXCL12 Overexpression in
Tipifarnib Responders
Separately, Kura has been evaluating the potential to use CXCL12
pathway biomarkers to enrich for clinical activity in other
hematologic malignancies. In addition to AITL, high CXCL12
expression was observed in tumors from other lymphoma patients,
including patients with PTCL-NOS, diffuse large B-cell lymphoma
(DLBCL) and mycosis fungoides, the most common form of cutaneous
T-cell lymphoma (CTCL). Lymphoma patients with CXCL12 reference
sequences also appeared to have a higher chance of clinical benefit
from tipifarnib treatment. The identification of these CXCL12
reference sequences in responders to tipifarnib across multiple
hematologic malignancies will be presented in a poster presentation
at 17:30 CET / 11:30 am ET tomorrow at the EHA Annual Congress in
Amsterdam. A copy of the poster is also available on the Company’s
website at www.kuraoncology.com.
“These data represent the first prospective validation of CXCL12
pathway biomarkers to enrich for clinical activity of tipifarnib in
PTCL. We believe these data support the potential to register
tipifarnib in both the AITL and PTCL-NOS patient populations, and
we look forward to seeking regulatory feedback on next steps for
this program,” said Troy Wilson, Ph.D., President and CEO of Kura
Oncology. “In addition, based on our growing body of clinical and
preclinical data, we believe CXCL12 pathway biomarkers may have the
potential to unlock the therapeutic value of farnesyl transferase
inhibition across multiple hematologic and solid tumor indications,
including DLBCL, acute myeloid leukemia (AML), CTCL and pancreatic
cancer.”
Conference Call and Webcast
Kura’s management will host a webcast and conference call at
8:00 a.m. ET today, June 14, 2019 to discuss the results from the
Company’s Phase 2 trial of tipifarnib in PTCL. The live call may be
accessed by dialing (877) 516-3514 for domestic callers or +1 (281)
973-6129 for international callers and using conference ID
#1273055. A live webcast of the call will be available from the
Investors and Media section of the Company’s website at
www.kuraoncology.com, and will be archived there for 30 days.
About Peripheral T-Cell Lymphoma
PTCL is a rare and diverse group of aggressive lymphomas that
develop from white blood cells called NK/T-cells that grow
abnormally. The term PTCL is sometimes used to describe a
heterogeneous group of T-cell lymphomas. The most common types of
PTCL are PTCL-NOS and AITL. Significant advances in the genetic
landscape of T-cell and NK-cell neoplasms as the result of genomic
studies, as well as the introduction of more powerful diagnostic
technologies have led to revisions in the classification and
introduction of new entities. Many of the same genetic changes
observed in AITL are also observed in cases of PTCL-NOS that
manifest a T follicular helper (TFH) phenotype. This common
genotype/phenotype has led to follicular T-cell lymphoma (FTCL) and
AITL being unified under a common heading. Cases of nodal PTCL with
TFH phenotype are now included in the same grouping as well. As a
result, patients with the PTCL-NOS phenotype are increasingly being
characterized as having AITL and/or related tumors.
Recently, the U.S. Food and Drug Administration (FDA) approved
ADCETRIS® (brentuximab vedotin) in combination with chemotherapy
for previously untreated systemic ALCL or other CD30-expressing
PTCL, including AITL and PTCL-NOS. This was the first FDA-approved
frontline treatment for PTCL. Previously approved therapies in
relapsed or refractory PTCL were based on single-arm clinical
trials of 130 patients or fewer with response rates in the range of
25-27% and limited duration of clinical benefit in unselected
populations.
About CXCL12
CXCL12 is a stroma-derived chemokine that promotes the
progression of lymphoma as well as other hematological and solid
tumors carrying the CXCR4 receptor. Results from ancillary studies
show that high CXCL12 expression is a negative prognostic factor
for standard-of-care PTCL therapy. Approximately 50% of the AITL
patients and 35% of the non-AITL patients in Kura’s Phase 2 trial
of tipifarnib in PTCL overexpressed CXCL12.
About Tipifarnib
Kura Oncology’s lead drug candidate, tipifarnib, is a potent,
selective and orally bioavailable inhibitor of farnesyl transferase
in-licensed from Janssen in December 2014. Previously, tipifarnib
was 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 been
determined that could explain its clinical activity across a range
of solid tumor and hematologic indications. 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, following an end of Phase 2 meeting with the FDA, Kura
initiated its first registration-directed trial of tipifarnib in
patients with recurrent or metastatic HRAS mutant head and neck
squamous cell carcinoma (HNSCC).
In 2018, the U.S. Patent and Trademark Office issued new patents
for tipifarnib as a method of treating patients certain
CXCL12-expressing cancers, including PTCL, and as a method of
treating patients with AITL. Both patents expand protection for
tipifarnib, providing exclusivity in the United States to 2037.
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 is conducting
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, which is
anticipated to enter into a Phase 1 clinical trial in mid-2019. For
additional information about Kura, 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 Kura’s product candidate tipifarnib, and progress and
expected timing of Kura’s drug development programs and clinical
trials. 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 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," "anticipates," "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 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
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