The Lancet Oncology Publishes Phase I Data Demonstrating the Safety, Tolerability, and Preliminary Efficacy of Cornerstone Pharmaceuticals’ CPI-613 in Combination with Modified FOLFIRINOX in Patients with Metastatic Pancreatic Cancer

Promising Efficacy Signal Appears to Exceed Current Standards of Care

Newark, New Jersey, UNITED STATES

Cranbury, NJ, May 09, 2017 (GLOBE NEWSWIRE) -- Cranbury, N.J., May 09, 2017 --(GlobeNewswire)-- Cornerstone Pharmaceuticals, Inc., a clinical-stage, oncology-focused pharmaceutical company, today announced the publication of data from a Phase I trial evaluating its lead compound, CPI-613, in combination with a modified FOLFIRINOX regimen in patients with metastatic pancreatic cancer. The data, published in the current issue of the Lancet Oncology, provides preliminary evidence of CPI-613 based combination therapy exhibiting efficacy improvement over currently approved treatments while also showing that the CPI-613 combination was safe and well tolerated.[1] 

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. By providing evidence of safety, tolerability, and preliminary efficacy, the Phase I data provides direction for further investigation of CPI-613 in combination with modified FOLFIRINOX in patients with metastatic pancreatic cancer, including a forthcoming Phase II/III trial of the combination. 

“Patients with metastatic pancreatic cancer have a dismal prognosis, and the toxicity of standard therapies limits their utility, underscoring the need for safer and more effective therapeutic approaches,” said lead investigator Angela Alistar, MD, Assistant Professor of Hematology and Oncology at Wake Forest School of Medicine in Winston-Salem, N.C. “Our results appear to support the rationale for combining CPI-613 with modified FOLFIRINOX in this underserved patient population.”

Pancreatic cancer is the fourth-leading cause of cancer-related death in the United States, with a 5-year survival rate of just 7%.[2] More than half (53%) of patients are diagnosed at the advanced stages of the disease,[2] when treatment is considered to be only palliative.[1] The most commonly used treatments are FOLFIRINOX, a four-drug combination consisting of 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin; and gemcitabine plus nab-paclitaxel. These treatments provide a median overall survival of 11.1 months and 8.5 months, respectively.[3],[4] However, long-term survival has been reported to be rare with these agents, and their toxicity usually restricts their use to patients with good performance status.

“Substantial changes in mitochondrial metabolism have been observed in patients with pancreatic cancer,” noted Dr. Alistar. “Preclinical research suggests that targeting the TCA cycle with an agent such as CPI-613 can disrupt the metabolic reprogramming that occurs as the disease progresses, thereby inducing apoptosis, necrosis, and autophagy of tumor cells. We therefore hypothesized that combining CPI-613 with modified FOLFIRINOX would lead to enhanced therapeutic efficacy with little to no additional toxicity.”

About the Phase I Study

Dr. Alistar and colleagues conducted a Phase I, open-label, dose-escalation trial to determine the maximum tolerated dose (MTD) of CPI-613 when used in combination with modified FOLFIRINOX (oxaliplatin at 65 mg/m2, irinotecan at 140 mg/m2, and 5-fluorouracil 400 mg/m2 bolus and 2400 mg/m2 over 46 hours) in patients with newly diagnosed metastatic pancreatic cancer. The trial employed a two-stage dose-escalation scheme (single patient and traditional 3+3 design). In the single-patient stage, one patient was accrued per dose level. The starting dose of CPI-613 was 500 mg/m2 per day; the dose level was then escalated by doubling the previous dose if there was no CPI-613-related toxicity greater than Grade 2 within 4 weeks. The traditional 3+3 dose-escalation stage was triggered if CPI-613-related toxicity was Grade 2 or greater. The dose level for CPI-613 for the first cohort in the first dose-escalation stage was the same as that used in the last cohort of the single-patient dose-escalation stage. Secondary objectives were safety, preliminary efficacy, and tissue collection for future analyses.[1]

The trial enrolled 20 patients. The MTD of CPI-613 was 500 mg/m2; the median number of treatment cycles administered at the MTD was 11 (interquartile range, 4-19). Among the 18 patients treated with the MTD, the objective response rate (ORR, defined as complete responses [CR] plus partial responses [PR]) was 61% (11/18). Three patients had a CR, one had a non-CR/non-progressive disease, seven experienced a PR, three had stable disease, and four experienced progressive disease.[1] The ORR exceeded those reported in recent trials of FOLFIRINOX (32%)[3] and gemcitabine plus nab-paclitaxel (23% to 29%)[4], further underscoring the potential utility of CPI-613-based combination therapy.

“I am very excited by the results of this study, which provide strong preliminary evidence that the combination of CPI-613 with modified FOLFIRINOX is well tolerated and results in durable therapeutic responses in patients with advanced adenocarcinoma of the pancreas,” said Boris Pasche, MD, PhD, director of the Wake Forest Baptist Comprehensive Cancer Center and senior author of the study. "Retrospective review of patients treated at our institution during the trial indicates that clinical efficacy of this new combination therapy appears to be markedly higher than FOLFIRINOX alone.”

“The Phase I data leads us to believe that CPI-613 in combination with modified FOLFIRNOX is a combination chemotherapy regimen that may be safer and more effective than current standards of care in metastatic pancreatic cancer,” commented Howard Jonas, Executive Chairman, Cornerstone Pharmaceuticals. “These encouraging results will inform the next steps of development for CPI-613-based combination therapy, in which we hope to validate the intriguing efficacy signals reported in the Lancet Oncology. Our plans include a pivotal trial of CPI-613 in combination with modified FOLFIRINOX, which we aim to initiate in 2017.”

About Cornerstone Pharmaceuticals, Inc.

Cornerstone Pharmaceuticals, Inc. is a 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

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Sanjeev Luther
Chief Operating Officer, Cornerstone Pharmaceuticals, Inc.

Jacob Jonas
Public Relations, Cornerstone Pharmaceuticals, Inc.


[1] Alistar A, Morris BB, Desnoyer R, et al. (2017). Safety and tolerability of the first-in-class agent CPI-613 in combination with modified FOLFIRINOX in patients with metastatic pancreatic cancer: a single-centre, open-label, dose-escalation, phase 1 trial. The Lancet Oncology. doi: 10.1016/S1470-2045(17)30314-5

[2] American Cancer Society. Cancer Facts & Figures 2016. Atlanta: American Cancer Society; 2016.

[3] Conroy T, Desseigne F, Ychou M, et al. (2011). FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med, 364(19), 1817-25. doi: 10.1056/NEJMoa1011923

[4] Von Hoff DD, Ervin T, Arena FP, et al. (2013). Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med, 369(18), 1691-1703. doi: 10.1056/NEJMoa1304369