New Data Presented at ESMO Congress 2019 from the Arginase Inhibitor INCB001158 Alone and in Combination with Pembrolizumab
September 29 2019 - 10:30AM
Calithera Biosciences, Inc. (Nasdaq: CALA), a clinical stage
biotechnology company focused on discovering and developing novel
small molecule drugs for the treatment of cancer and other
life-threatening diseases, today announced the presentation of new
data from the investigational first-in-class oral arginase
inhibitor INCB001158 as a monotherapy and in combination with the
checkpoint inhibitor pembrolizumab in microsatellite stable (MSS)
colorectal carcinoma patients. The data were presented during an
oral Proffered Paper session at the European Society for Medical
Oncology (ESMO) Congress 2019 taking place in Barcelona, Spain
(Abstract #440O). Calithera has a global collaboration and license
agreement with Incyte Corporation for the joint research,
development and commercialization of INCB001158 in hematology and
oncology.
“We are pleased to share initial data from the trial of
INCB001158 in MSS colorectal carcinoma that is refractory to
standard therapies, a disease that has very low historical average
response rates to checkpoint inhibitors such as pembrolizumab,”
said Susan Molineaux, PhD, president and chief executive officer of
Calithera. “We are pleased with the progress of this program as we
seek to develop a first-in-class product for patients with multiple
types of solid tumors.”
Calithera and Incyte are collaborating to conduct this Phase 1
study evaluating INCB001158 as monotherapy and in combination with
the PD-1 inhibitor pembrolizumab in checkpoint inhibitor refractory
and naïve advanced/metastatic solid tumors. Data were presented as
of the data cut-off of July 22, 2019. The study was designed as a
dose escalation of INCB001158 alone and in combination with
pembrolizumab followed by expansion cohorts which followed a Simon
2 Stage design. There were three monotherapy expansion cohorts
(non-small cell lung cancer, colorectal carcinoma and other solid
tumors) and eight combination expansion cohorts, including
PD-(L)1-naïve (MSS colorectal carcinoma, head and neck cancer,
gastric cancer, mesothelioma) and PD-(L)1 refractory (non-small
cell lung cancer, urothelial carcinoma, melanoma, and MSI
colorectal carcinoma) patients.
Combination Results
- The PD-(L)1-naïve MSS colorectal carcinoma (CRC) patient cohort
has advanced to stage 2 of a Simon 2-stage design. Among 43
response-evaluable patients who had received a median of 3 prior
therapies, 3 patients achieved a confirmed partial response (7%);
the historical overall response rate is 0-1% in second- and
third-line MSS CRC patients treated with checkpoint inhibitor
therapies. Two of the three responders are ongoing at the time of
data cutoff with a duration of response of 2.4+ and 7+ months
respectively. The third responder had a duration of response of 6.7
months. The six month PFS rate for the cohort was 20%.
- Pharmacodynamic increases in total intratumoral CD8+ cells were
seen post-treatment with INCB001158 + pembrolizumab in MSS CRC
patients.
Monotherapy Results
- The colorectal carcinoma monotherapy cohort has advanced to
stage 2 of a Simon 2-stage design. Among 33 response-evaluable MSS
CRC patients, one patient achieved a confirmed partial response
(3%) and one patient achieved stable disease lasting seven months.
Both patients had disease progression within six months on their
immediately preceding line of therapy. The disease control rate for
the monotherapy MSS CRC cohort was 27%.
- INCB001158 inhibited plasma arginase activity at all doses and
induced dose-related increases in plasma arginine, including a mean
three-fold increase at the recommended phase 2 dose of 100 mg
bid.
Safety
- A total of 85 patients with advanced solid tumors were treated
with INCB001158 as a monotherapy in doses of 50 to 150mg bid and
were evaluable for safety. A maximum tolerated dose was not
reached. Immune-related adverse events included one dose-limiting
toxicity (DLT) each of Grade 2 malaise (at 150mg) and Grade 3
colitis (100mg). Clinically significant urea cycle inhibition was
not seen.
- A total of 114 PD-(L)1-naïve and PD-(L)1 refractory patients
were treated in INCB001158 in combination with pembrolizumab and
evaluable for safety across multiple disease specific cohorts. The
overall frequency and severity of immune related adverse events was
consistent with the pembrolizumab safety profile.
About INCB001158 (CB-1158)
INCB001158 (CB-1158) is an investigational first-in-class, novel
small molecule arginase inhibitor. Arginase is an enzyme that
suppresses the immune-mediated destruction of tumors by depleting
levels of a key amino acid, L-arginine, from the tumor
microenvironment. A number of cell types in the tumor
microenvironment, including myeloid-derived suppressor cells,
macrophages, and neutrophils, can secrete arginase. L-arginine
deprivation can act via nutrient sensor pathways to exert several
suppressive effects on T-cell function, inhibiting proliferation,
decreasing cytokine production, and diminishing expression of the
T-cell receptor CD3ζ chain. Arginase activity may thus impair
T-cell mediated anti-tumor responses. INCB001158 is being developed
in a global collaboration with Incyte Corporation.
About Calithera
Calithera Biosciences is a clinical-stage biopharmaceutical
company pioneering the discovery and development of targeted
therapies that disrupt cellular metabolic pathways to
preferentially block tumor cells and enhance immune-cell activity.
Driven by a commitment to rigorous science and a passion for
improving the lives of people impacted by cancer and other
life-threatening diseases, Calithera is advancing a pipeline of
first-in-clinic, oral therapeutics to meaningfully expand treatment
options available to patients. Calithera is headquartered in South
San Francisco, California. For more information about Calithera,
please visit www.calithera.com.
Forward Looking Statements
Statements contained in this press release regarding matters
that are not historical facts are "forward-looking statements"
within the meaning of the Private Securities Litigation Reform Act
of 1995. Words such as "may," "will," "expect," "anticipate,"
"estimate," "intend," "poised" and similar expressions (as well as
other words or expressions referencing future events, conditions,
or circumstances) are intended to identify forward-looking
statements. These statements include those related to the safety,
tolerability and efficacy of Calithera’s product candidates, the
overall advancement of Calithera’s product candidates in clinical
trials, the unmet need in the treatment of patients with advanced
disease, and Calithera’s plans, and those of its collaboration
partners, to continue development of its product candidates.
Because such statements are subject to risks and uncertainties,
actual results may differ materially from those expressed or
implied by such forward-looking statements. The product candidates
that Calithera develops may not progress through clinical
development or receive required regulatory approvals within
expected timelines or at all. In addition, clinical trials may not
confirm any safety, potency or other product characteristics
described or assumed in this press release. Such product candidates
may not be beneficial to patients or successfully commercialized.
The failure to meet expectations with respect to any of the
foregoing matters may have a negative effect on Calithera's stock
price. Additional information concerning these and other risk
factors affecting Calithera's business can be found in Calithera's
most recent Quarterly Report on Form 10-Q filed with the Securities
and Exchange Commission, and other periodic filings with the
Securities and Exchange Commission at www.sec.gov. These
forward-looking statements are not guarantees of future performance
and speak only as of the date hereof, and, except as required by
law, Calithera disclaims any obligation to update these
forward-looking statements to reflect future events or
circumstances.
SOURCE: Calithera Biosciences,
IncorporatedCONTACT:Jennifer McNealey
ir@Calithera.com650-870-1071
MEDIA CONTACT: Hannah Hurdle
hannahhurdle@sambrown.com 805-338-4752
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