Poniard Pharmaceuticals, Inc. has announced that it is presenting safety and efficacy data in prostate cancer patients from its Phase 1 study of picoplatin, the Company's lead product candidate, at the 2008 Genitourinary (GU) Cancers Symposium, a meeting of the American Society of Clinical Oncology (ASCO) that is being held in San Francisco.
The poster presentation includes safety and efficacy data from a dose-escalating Phase 1 study of picoplatin in combination with full-dose docetaxel (75 mg/m squared) with prednisone as a first-line treatment for metastatic hormone refractory prostate cancer (mHRPC).
The Phase 1 study sought to establish the maximum tolerated dose of picoplatin and provide information on the safety and efficacy of picoplatin in combination with docetaxel and prednisone, the standard of care for the first-line treatment of mHRPC.
"The data we have generated with picoplatin in prostate cancer indicate a PSA (prostate specific antigen) response of 65 percent which suggests an improvement compared to docetaxel therapy alone," said Jerry McMahon, Ph.D., chairman and CEO of Poniard Pharmaceuticals.
"In addition, the tolerability of picoplatin with full-dose docetaxel supports our ongoing Phase 2 study that we believe will confirm and extend these initial findings. The combination of platinums and taxanes, such as docetaxel, is used to treat many other solid tumors, such as non-small cell and ovarian cancers. We believe that our data support additional evaluation of picoplatin and docetaxel combinations in these cancers in addition to prostate cancer."
In the combination Phase 1 dose-escalating study, 33 patients were treated with one of four doses (60, 80, 100 or 120 mg/m squared) of picoplatin, as well as either 60 mg/m squared or 75 mg/m squared (full-dose) docetaxel plus 5 mg prednisone twice daily. Nine patients received 120 mg/m squared picoplatin and 75 mg/m squared docetaxel every 21 days plus 5 mg prednisone twice daily. This dose, which is also the dose currently under study in the Phase 2 trial, was well tolerated.
Hematological toxicity, including neutropenia, anemia and thrombocytopenia, was dose-dependent and reversible. Neutropenia was the dose-limiting toxicity (DLT). Mild neuropathy (grade 1) was observed in 3 of 33 patients (9 percent) and was unrelated to cumulative picoplatin dose. Neuropathy was infrequent, and no neuropathy of grade 2 or greater was observed. PSA response rate was 65 percent (20 of 31 evaluable patients).
Survival data are not yet available. Patient withdrawal from study treatment occurred from death in four patients, progressive disease in eight patients, and withdrawal of consent in one patient. Patients in the Phase 1 trial received a median number of 7 cycles, and 13 of 33 patients completed the maximum of 10 cycles of treatment according to the study protocol.
Based on safety and efficacy data from the Phase 1 study, the recommended Phase 2 regimen of intravenous picoplatin (120 mg/m squared) and docetaxel (75 mg/m squared) every 21 days with prednisone (5 mg) orally twice daily is being evaluated in a Phase 2 study in chemotherapy naive mHRPC patients.
PSA response is the primary endpoint; secondary endpoints include radiological response using RECIST criteria, time to progression and survival (1-year, progression-free and overall). The Phase 2 trial completed enrollment in December 2007. The Company expects to present the results of this study in scientific forums later this year.