NEWTOWN, Pa., & PENNINGTON, N.J.--(BUSINESS WIRE)--Onconova Therapeutics, Inc. announced two advances in the clinical development of ESTYBON (rigosertib, ON 01910.Na) in presentations at the annual meeting of the American Society of Clinical Oncology (ASCO), June 3-7, 2011, in Chicago, Illinois. Based on the positive trial results presented at the meeting, Onconova also announced the initiation of a Phase II/III study for pancreatic cancer.
The first study presented at ASCO highlights the positive results of a Phase I clinical trial in patients with advanced pancreatic cancer and other solid tumors treated with a combination of rigosertib and gemcitabine. This combination will be studied in a new Phase II/III trial. In addition, a second report published by ASCO presents positive results of a Phase I study in solid tumor patients treated with a combination of oxaliplatin and rigosertib.
“This research being presented at ASCO signifies the commitment of Onconova to find novel treatment solutions and improve the lives of patients with cancer,” said Robert Maguire, M.D., Distinguished Clinical Fellow for Onconova. “We are excited to present data on the safety, tolerability, and preliminary efficacy of rigosertib with promising results in the treatment of pancreatic cancer and other advanced solid tumors. We are pleased that this study has led to the design and the initiation of the Phase II/III study for pancreatic cancer.”
The new clinical trial, designated ONTRAC (ON 01910.Na TRial in Patients with Advanced Pancreatic Cancer), is a Phase II/III, multicenter, randomized, controlled study to compare the efficacy and safety of gemcitabine alone vs. gemcitabine combined with rigosertib (ON 01910.Na) in patients with previously untreated metastatic pancreatic cancer.
The ONTRAC trial represents the most advanced clinical trial to date of rigosertib in combination with chemotherapeutic agents. Previous published non-clinical studies have suggested additive or synergistic activity when various chemotherapeutic agents are used in combination with rigosertib.
“The ability to overcome resistance to chemotherapy, which is commonly encountered in pancreatic cancer, with the addition of a novel agent, would be an important step forward for patients,” said Antonio Jimeno, M.D., Ph.D., Associate Professor, University of Colorado Hospital, who has explored combination therapy with rigosertib in pancreatic cancer. “The tolerability of the rigosertib/gemcitabine combination has allowed patients to begin treatment with a full dose of each agent in the proposed randomized Phase II/III trial.”
Rigosertib is also being evaluated in a pivotal Phase III trial in myelodysplastic syndrome (MDS), the ONTIME (ON 01910.Na Trial In Myelodysplastic SyndromE) trial. This trial is being conducted under a Special Protocol Assessment (SPA) agreement with the FDA. Additional information on all Onconova clinical trials is available at www.clinicaltrials.gov.
ASCO presentations on ESTYBON (rigosertib):
Abstract# 3101
“Final results of a phase 1 study of the combination of a novel cell cycle inhibitor ON 01910.Na with gemcitabine in patients with advanced pancreatic and other solid tumors”
Ma WW, Messersmith WA, Dy GK, Freas E, Whitworth A, Wilhelm F, Eckhardt SG, Adjei A, Jimeno A.
Category: Developmental Therapeutics - Experimental Therapeutics
Sub-category: PI3-Akt-mTOR Pathway
Time: Monday June 6, 8:00 AM to 12:00 PM
Location: McCormick Place Hall A
Dr. Ma and colleagues from Roswell Park Cancer Institute and University of Colorado School of Medicine presented final results of a phase I study of the combination of rigosertib and gemcitabine in 36 patients with advanced pancreatic cancer and other solid tumors. Only toxicities related to gemcitabine were observed and preliminary antitumor activity was measured in several patients, suggesting that rigosertib and gemcitabine is a well-tolerated combination with a promising basis for phase II evaluation in advanced metastatic pancreatic cancer patients.
Abstract# e13584
“Final results of a phase 1 dose-escalation study of ON 01910.Na in combination with oxaliplatin in patients with advanced solid tumors”
Ohnuma T, Holland JF, Goel S, Wilck E, Lehrer D, Ghalib MH, Chaudhary I, Wilhelm F, Swami U, Mani S.
Category: Developmental Therapeutics - Experimental Therapeutics
Session Title: New Targets, New Technologies
(Publication only, also published at ASCO on-line)
Dr. Ohnuma and colleagues from Mount Sinai School of Medicine, Montefiore Medical Center and Onconova Therapeutics will publish the final results of a dose-escalation study of rigosertib in combination with oxaliplatin in patients with advanced solid tumors. No dose limiting toxicity was seen in rigosertib treated patients and confirmed partial responses and stable disease were observed in several patients, leading to the conclusion that this combination was well-tolerated and resulted in objective tumor responses in advanced ovarian, breast, colon and renal cancer patients.
About ONTRAC
ONTRAC (ON 01910.Na TRial in Patients with Advanced Pancreatic Cancer) is a Phase II/III, multicenter, randomized, controlled study to compare the efficacy and safety of gemcitabine alone vs. rigosertib combined with gemcitabine in patients with previously untreated metastatic pancreatic cancer. The trial is expected to enroll pancreatic cancer patients in both the United States and India. The primary end point of the study is overall survival and the secondary end points are progression-free survival, objective response rate, safety/tolerability, and quality of life. The ClinicalTrials.gov identifier for ONTRAC is NCT01360853.
About ONTIME
ONTIME (ON 01910.Na Trial In Myelodysplastic SyndromE) is a Phase III, multicenter, randomized, trial of best supportive care plus rigosertib treatment compared to best supportive care alone, designed to determine the efficacy and safety of rigosertib in higher-risk MDS patients with excess blasts (5% to 30% bone marrow blasts), who are refractory, intolerant to, or have relapsed after azacitidine or decitabine treatment. The trial is expected to enroll MDS patients in both the United States and Europe. The ClinicalTrials.gov identifier for ONTIME is NCT01241500.
ESTYBON (rigosertib, ON 01910.Na) is a small molecule inhibitor of critical pathways important in the growth and proliferation of cancer cells. Extensive Phase I and Phase II studies with ESTYBON have been conducted in patients with solid tumors and hematological cancers, including MDS, pancreatic and ovarian cancers. Based on data from clinical studies that explored various dose regimens of rigosertib, administered alone or in combination with other chemotherapeutic agents, in patients with myelodysplastic syndrome (MDS) or with advanced solid tumors, rigosertib is overall well tolerated. The most frequent drug-related adverse events (reported by at least 10% of patients) in the MDS population were fatigue, dysuria, abdominal pain, nausea and diarrhea. In patients with advanced solid tumors, the most frequent (>10%) were anorexia, diarrhea, vomiting, nausea, and fatigue. The majority of these drug-related adverse events were Grade 1 or 2 in severity (NCI CTCAE). In phase I and II clinical trials in patients who have a limited number of approved treatments for their diseases, ESTYBON has demonstrated in those patients with available follow up data, significant bone marrow responses (at least 50% blast reduction) in 53% of MDS patients and >50% reduction in CA 19-9 marker in about 36% of pancreatic cancer patients. The ONTIME and ONTRAC studies of ESTYBON are designed to further investigate these results and address the unmet medical needs for MDS and pancreatic cancer patients. A U.S. Patent covering ESTYBON was issued in October 2009 and European and other international patents are expected to issue shortly.
About Pancreatic cancer
Pancreatic cancer is the 4th most common cause of cancer deaths in the US and worldwide. With 43,000 cases diagnosed in the United States in 2010, and 36,800 deaths, pancreatic cancer has one of the highest fatality rates of all cancers in the United States among both men and women. Pancreatic cancer is responsible for 6% of cancer deaths each year. The median survival for pancreatic cancer is about 6 months . Current chemotherapeutic options have little impact on the prognosis or outcome of the disease.
About Onconova Therapeutics, Inc.
Onconova, based in Newtown, PA, and Pennington, NJ, discovers and develops novel small molecule therapeutics targeting signal transduction, cell-cycle, and DNA repair pathways. Onconova has a novel discovery platform focusing on non-ATP competitive kinase inhibitors, and the company is also exploring a new immunoconjugate technology (comprising potent active compounds and proprietary linkers) for arming monoclonal antibodies for cancer therapy. These products, technologies, and candidates are derived internally from a proprietary library of new chemical entities. In addition to ESTYBON, Onconova is also developing Ex-RAD® (ON 01210.Na) as a novel radiation protection drug (oral and injection) in collaboration with the U.S. Department of Defense to protect against radiation injury of tissue and whole body. For additional information, please visit http://www.onconova.com.