Picoplatin Safety Data in Colorectal Cancer
Poniard Pharmaceuticals, Inc. (NASDAQ:PARD) , a biopharmaceutical company focused on oncology, today announced that it has presented safety data from a Phase 1 dose-escalation study of picoplatin, the Company's lead product candidate, at the 2008 Gastrointestinal Cancers Symposium, a meeting of the American Society of Clinical Oncology (ASCO) which is being held in Orlando, Fla.
The poster presentation included safety data from a Phase 1 study of picoplatin in combination with 5-fluorouraciltermtermtermterm (5FU) and leucovorintermterm (LV) as a first-line treatment for metastaticterm colorectal cancer (mCRC). The Phase 1 study seeks to establish the maximum tolerated dose of picoplatin and provide information on the safety of picoplatin when combined with 5FU and LV for the treatment of colorectal cancer. Promising safety data observed from the study to date formed the basis for further development of picoplatin in our ongoing Phase 2 trial in mCRC.
"These study results suggest that picoplatin does not cause severe neurotoxicity, as is commonly seen in mCRC patients treated with the regimen of 5FU and LV with oxaliplatintermterm," said Jerry McMahon, Ph.D., chairman and CEO of Poniard Pharmaceuticals. "Picoplatin has demonstrated both good tolerability and no severe neuropathies when combined with 5FU and LV. We believe picoplatin has the potential to be a preferred platinum for the treatment of colorectal and other cancer indications."
Current National Comprehensive Cancer Network (NCCN) guidelines encourage the discontinuation of FOLFOXterm (5FU and LV with oxaliplatin) after three months of therapy or sooner if significant (Grade 3 or greater) neurotoxicity develops. For more information, please see http://www.nccn.org/.
In the Phase 1 study, 50 patients were treated with picoplatin on either an every-two-week or an every-four-week basis in combination with the standard of care every-two-week dose of 5FU and LV. Patients received up to 28 cycles, and the therapy was well tolerated. Increased hematological toxicity was observed at higher doses. None of the patients treated with picoplatin exhibited a Grade 3 or higher neuropathy and only 9 of 45 patients (20 percent) experienced mild neuropathy. No neuropathy of Grade 2 or greater was observed in the 26 patients who received greater than or equal to 400 mg/m squared picoplatin. Mild nephro- and oto- toxicity were observed infrequently. The dose limiting toxicity (DLT) was most frequently hematological with neutropenia and thrombocytopenia. The maximum tolerated dose was established in the every-four-week schedule at 150 mg/m squared. The maximum tolerated dose for the every-two-week schedule has not yet been reached.
Based on the evidence of a more attractive safety profile of picoplatin in this combination (FOLPI) compared to the standard of care regimen with oxaliplatin (FOLFOX) as well as clinical activity in the Phase 1 study, the Company initiated a randomized Phase 2 trial in November, 2007 to evaluate intravenous picoplatin in the first-line treatment of mCRC. The Phase 2 trial is intended to generate proof-of-concept data to further evaluate efficacy and safety, including neuropathy of picoplatin in combination with 5-FUterm and LV (FOLPI versus FOLFOX) and to provide support for a potential registrational Phase 3 trial. The Company expects to present data from the Phase 1 and 2 mCRC program in scientific forums around mid year.
Picoplatin is an intravenous chemotherapeutic agent that has an improved safety profile compared to existing platinum-based chemotherapeutics. It was designed to overcome platinum resistance associated with the treatment of solid tumors. Picoplatin has been evaluated in more than 750 patients and has demonstrated activity in multiple indications with no evidence of significant kidney, nerve toxicity or hearing loss, toxicities commonly observed with other platinum chemotherapyterm drugs.
In addition to the Phase 2 clinical trial in patients with mCRC, Poniard is evaluating intravenous picoplatin in an ongoing pivotal Phase 3 trial, known as SPEAR (Study of Picoplatin Efficacy After Relapse), in small cell lung cancer. This registrational trial is being conducted under a Special Protocol Assessment (SPA) from the U.S. Food and Drug Administration (FDA) and is evaluating overall survival as the primary endpoint. The Company also is evaluating intravenous picoplatin in an ongoing Phase 2 clinical trial for the treatment of hormone refractory prostate cancer (HRPC). Oral picoplatin is being evaluated in a Phase 1 clinical trial in solid tumors.