Onconova to initiate ESTYBON Phase II/III study in pancreatic cancer

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 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.”

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.