Poniard Pharmaceuticals, Inc. (PARD), a biopharmaceutical company focused on innovative oncology therapies, announced final data from a randomized, controlled phase 2 trial of picoplatin in metastatic colorectal cancer (CRC) patients. The study met its primary objective, as picoplatin in combination with 5-fluorouracil and leucovorin (FOLPI regimen) was associated with a statistically significant reduction in neurotoxicity (p <0.004) compared to oxaliplatin given in combination with 5-fluorouracil and leucovorin (FOLFOX regimen). Results also suggested that FOLPI had similar efficacy to FOLFOX.
"We believe that these Phase 2 data confirm picoplatin's potential as an alternative to oxaliplatin in the first-line treatment of metastatic CRC and will support the design of a phase 3 study," said Jerry McMahon, Ph.D., chairman and CEO of Poniard. "We plan to schedule an end of phase 2 meeting with the US Food and Drug Administration to discuss these data and a potential registration strategy for picoplatin in CRC. Our ultimate goal is to secure a strategic partnership to support further development of picoplatin in CRC and other solid tumour indications, including prostate and ovarian cancers."
The picoplatin phase 2 CRC data were presented at the American Society of Clinical Oncology's 2010 Gastrointestinal Cancers Symposium in Orlando, Florida., during today's General Poster Session.
The randomized, controlled phase 2 trial evaluated picoplatin as a neuropathy-sparing alternative to oxaliplatin for the first-line treatment of metastatic CRC in 101 patients who had not received prior chemotherapy. The trial's primary objective was to measure the relative incidence and severity of neuropathy in the FOLPI regimen compared to the FOLFOX regimen. In addition, the study measured comparative safety and efficacy (assessed by disease control, progression-free survival (PFS) and overall survival (OS)) data; however, the study was not powered to assess the statistical significance of these secondary endpoints. The final phase 2 data indicated that:
FOLPI is associated with a statistically significant reduction in neurotoxicity compared to FOLFOX (HR <0.30; p <0.004). Neuropathy, regardless of Grade, was 26 per cent in FOLPI-treated patients and 62 per cent in FOLFOX-treated patients. No Grade 3/4 neuropathy was observed with FOLPI.
FOLPI had similar efficacy to FOLFOX as measured by: Disease Control of 75 per cent and 76 per cent for FOLPI and FOLFOX, respectively; (Relative risk 1.02 (95 per cent Confidence Interval (CI) 0.79-1.32), p=0.9); PFS of 6.8 months and 7.0 months for FOLPI and FOLFOX, respectively: HR 0.95 (95 per cent CI 0.63-1.45), p=0.82; OS of 13.6 months and 15.6 months for FOLPI and FOLFOX, respectively: HR 1.17 (95 per cent CI 0.72-1.91), p=0.53; Six-month and one-year survival rates were 80 per cent and 52 per cent for FOLPI and 83 per cent and 55 per cent for FOLFOX, respectively.
Picoplatin is a new and differentiated platinum-based chemotherapeutic agent that is in clinical development for multiple cancer indications, treatment combinations and by two routes of administration. It is designed to overcome platinum resistance associated with chemotherapy in solid tumours. Study data to date suggest that picoplatin has an improved safety profile relative to existing platinum-based cancer therapies and can be safely administered in combination with multiple approved oncology products. Approximately 1,100 patients have received picoplatin. Results obtained to date suggest that hematologic events are common but manageable. Kidney toxicity (nephrotoxicity) and nerve toxicity (neurotoxicity) are less frequent and less severe than is commonly observed with other platinum chemotherapy drugs. Picoplatin has demonstrated anti-tumor activity in a variety of solid tumours.
In addition to the phase 2 clinical trial of picoplatin in patients with metastatic CRC, Poniard has evaluated intravenous picoplatin in the treatment of small cell lung cancer in its phase 3 SPEAR trial. This trial did not meet its primary endpoint of overall survival, and the Company plans to meet with the FDA to discuss a potential regulatory path forward for picoplatin in this indication. Poniard is also evaluating picoplatin in a phase 2 clinical trial in patients with metastatic hormone-refractory prostate cancer. Final results of the Company's phase 1 cardiac safety trial and the phase 1 trial of an oral formulation of picoplatin were presented in 2009.