CRANBURY, N.J., Dec. 5, 2016 /PRNewswire/ -- Cornerstone
Pharmaceuticals, Inc., a privately held, clinical-stage,
oncology-focused pharmaceutical company, today presented data from
two Phase I trials evaluating its lead compound, CPI-613, in poster
sessions at the 58th annual meeting of the American Society of
Hematology (ASH) in San Diego,
California. The two datasets show encouraging efficacy and
safety results in patients with acute myeloid leukemia (AML) and
T-cell non-Hodgkin's lymphoma (T-cell NHL), respectively,
supporting the clinical rationale for combining CPI-613 with
standard chemotherapy in two hematologic malignancies that have
historically been difficult to treat.
CPI-613 is Cornerstone Pharmaceuticals' lead Altered Energy
Metabolism Directed (AEMD) drug candidate, a first-in-class
anticancer compound designed to disrupt the altered energy
production pathways in cancer cells by targeting mitochondrial
metabolism. It selectively targets the mitochondrial tricarboxylic
acid (TCA) cycle in cancer cells, an indispensable process
essential to cell multiplication and survival. The two datasets
presented at ASH are from the first reported studies of
CPI-613-based combination therapy in patients with AML and T-cell
NHL.
"Our ASH data presentations underscore the viability of
targeting the TCA cycle as a novel approach to anticancer
treatment," said Howard Jonas,
Chairman of the Board, Cornerstone Pharmaceuticals. "The results
suggest that blood-based disorders such as acute myeloid leukemia
and T-cell non-Hodgkin's lymphoma are amenable to combination
therapy with CPI-613, potentially filling unmet medical needs in
these underserved patient populations."
AML Data
In the first poster presentation, researchers
presented data from an open-label Phase I dose-escalation trial
designed to determine the maximum tolerated dose (MTD), safety, and
efficacy of CPI-613 administered intravenously in combination with
high-dose cytarabine (HiDAC) and mitoxantrone in patients with
relapsed or refractory AML. A total of 67 patients (median age of
60 years, with ages ranging from 21-79 years) were enrolled, of
whom 62 were ultimately evaluable. The overall response rate (ORR)
was 50%, including 26 patients in complete remission (CR) and 5 in
CR with incomplete blood count recovery (CRi); median survival was
6.7 months. Response was significantly associated with survival,
with a median survival of 13.2 months in responders versus 3 months
for all others.
Among 24 patients with poor-risk cytogenetics, the ORR was 46%
(9 CR + 2 CRi), with a median survival of 5.5 months. The
researchers described this result as "surprising," given data from
a historical cohort of patients treated with HDAC, mitoxantrone,
and asparaginase, in which only 19% (3/16) of patients with
poor-risk cytogenetics responded, with a median survival of 2.8
months (p=0.0571 for the comparison between CPI-613-based
combination therapy and the historical cohort). Among 15 elderly
(age ≥60 years) patients with poor-risk cytogenetics, CPI-613-based
combination therapy was associated with a significant improvement
in overall survival, compared to the historical cohort (p=0.
0359).
The most common toxicities in patients receiving CPI-613-based
combination therapy were diarrhea and nausea. Thirteen patients
(21%) went on to receive allogeneic stem cell transplantation.
"Combination therapy with CPI-613 is a novel approach to the
treatment of refractory acute myeloid leukemia, especially in
elderly patients and those with poor-risk cytogenetics," commented
lead investigator Timothy S. Pardee,
MD, PhD, Associate Professor, Internal Medicine, in the Section on
Hematology and Oncology at the Comprehensive Cancer Center of Wake
Forest Baptist Medical Center in Winston-Salem, North Carolina, Chief
Oncologist, Cornerstone. "It appears to improve overall survival
without increasing the toxicity of high-dose cytarabine, and
mitoxantrone. In addition to its direct effects on leukemia cells,
inhibition of the TCA cycle may alter immune responses in the tumor
microenvironment. Additionally, the availability of gene expression
profiling and other technologies may help identify patients likely
to respond to CPI-613, a benefit that may facilitate targeting of
metabolic pathways as a logical step in the evolution of anticancer
therapy."
T-cell NHL Data
In the second poster presentation,
researchers presented data from a Phase I, open-label, modified 3+3
dose-escalation trial evaluating the combination of CPI-613 and
bendamustine in patients with relapsed/refractory T-cell NHL.
CPI-613 was given at escalating doses starting at 2,000
mg/m2 over two hours on days 1-4 of the study, and on
days 8, 11, 15, and 18. Bendamustine was infused at 90
mg/m2 on days 4 and 5 of each four-week treatment cycle;
the treatment cycles were repeated up to six cycles. There was no
intra-patient dose escalation.
As of October 21, 2016, eight
patients had been dosed; all eight were evaluable for safety and
six were evaluable for efficacy. The most common grade 3 or higher
toxicities, lymphopenia and neutropenia, occurred in four patients.
The protocol was later amended to discontinue dose escalation at
doses of 2,750 mg/m2 or higher for dose-limiting
toxicities and to expand the 2,550 mg/m2 cohort.
The ORR was 83%. Three patients with peripheral T-cell lymphoma
not otherwise specified (NOS) attained a complete response. Two
patients – one with mycosis fungoides and one with
angioimmunoblastic T-cell lymphoma – had a partial response. One
patient with T-cell acute lymphoblastic leukemia experienced
progressive disease.
"There is no standard treatment for relapsed or refractory
T-cell lymphoma, highlighting an unmet clinical need among patients
living with this devastating group of hematologic malignancies,"
noted lead investigator Zanetta S.
Lamar, MD, Assistant Professor of Hematology/Oncology at
Wake Forest Baptist Medical Center in Winston-Salem, North Carolina. "This first
reported study of CPI-613 in combination with bendamustine in
patients with relapsed or refractory T-cell lymphoma showed a good
safety profile and an overall response rate exceeding 80%. Although
the numbers are small, these results warrant continued
investigation of this novel combination in this poor-risk patient
population."
About Cornerstone Pharmaceuticals, Inc.
Cornerstone Pharmaceuticals, Inc. is a privately held,
clinical-stage, oncology-focused pharmaceutical company committed
to the development and commercialization of therapies that exploit
the metabolic differences between normal cells and cancer cells.
Cornerstone's primary objective is to develop highly selective and
effective agents with minimal toxic effects on normal cells and
tissues. Cornerstone's first-in-class clinical lead compound,
CPI-613 is being evaluated in multiple Phase I, I/II, and II
clinical studies. The U.S. Food and Drug Administration (FDA) has
designated CPI-613 an orphan drug for the treatment of acute
myeloid leukemia (AML), pancreatic cancer and myelodysplastic
syndromes (MDS). The company's investors include IDT Corporation
(NYSE: IDT). For more information, visit:
www.cornerstonepharma.com.
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