ZIOPHARM Oncology, Inc. (Nasdaq: ZIOP) presented today at the 15th Annual Connective Tissue Oncology Society (CTOS) Meeting, positive interim data from the multicenter randomized Phase II trial of palifosfamide (ZymafosTM, ZIO-201) treating patients with unresectable or metastatic soft tissue sarcoma. As previously announced, having achieved the study-specified efficacy milestone following planned safety and efficacy review by the Data Committee, a panel of international sarcoma experts, and the Company’s Medical Advisory Board, it was determined that the data are compelling and sufficient to proceed to a pivotal study in support of product registration and to conclude enrollment in the trial.
The randomized Phase II trial treats patients with unresectable or metastatic soft tissue sarcoma in the front- and second-line setting. Patients are randomized either to doxorubicin (the only currently FDA-approved agent in sarcoma) or to palifosfamide in combination with doxorubicin. As of the October 5th cut-off date, there were 67 patients randomized to the trial, with 65 treated and 61 eligible for analysis. The 61 patients were evaluated for progression-free survival (PFS) with 20 documented PFS events (doxorubicin alone = 14 events; palifosfamide + doxorubicin = 6 events). With this analysis of all randomized and eligible patients, the hazard ratio is 0.63 favoring palifosfamide + doxorubicin (two-sided Wilcoxon-Gehan p-value = 0.026), statistically supporting that palifosfamide prolongs PFS by at least 50%.
The median PFS for doxorubicin is 4.4 months, the median PFS for palifosfamide + doxorubicin has not yet been reached; the 1st quartile PFS was 1.5 months for doxorubicin vs. 3.5 months for palifosfamide + doxorubicin (PFS more than doubled at this level). PFS is a biologically important end point in sarcoma, and has been well demonstrated to be a relevant measurement of the effect of treatment on outcome.
The arms of the trial were very well-balanced by predetermined stratification in terms of 1) Age (≥65 years and < 65 yrs) and 2) Pre-selected histopathological subtypes (leiomyosarcoma, synovial sarcoma and “other”). In addition, and consequently, this also resulted in balance between front- and second-line patients.
The interim safety data indicate that the addition of palifosfamide does not add to the toxicity of single agent doxorubicin. The most frequently reported side effects in both arms of the study include neutropenia and fatigue, hypokalemia, nausea, anemia, leucopenia, and alopecia. Palifosfamide is easily administered as an out-patient treatment, and generally well-tolerated.
“These interim results are very promising, indicating a potentially new drug to help control this life-threatening disease with acceptable safety and quality of life,” commented George Demetri, MD, Director of the Center for Sarcoma and Bone Oncology and the Ludwig Center at the Dana-Farber Cancer Institute and Harvard Medical School, and a member of ZIOPHARM’s Medical Advisory Board, whose experience includes having served as lead investigator in the clinical trials leading to the approval of GleevecTM and Sutent TM to treat GIST, a form of soft tissue sarcoma.
“These data are not only encouraging for sarcoma but hopefully palifosfamide may also work in treating other cancers. This is particularly interesting if the oral form is successful in the clinic,” added Lawrence Einhorn, MD, Distinguished Professor at the Simon Cancer Center of Indiana University Medical Center, Lance Armstrong Foundation Chair in Oncology, former President of ASCO and also a member of ZIOPHARM’s Medical Advisory Board, whose experience includes having served as the principal investigator in the development of ifosfamide in curing testicular cancer.
The Company is in the process of finalizing a registration trial plan in soft tissue sarcoma for review by the appropriate U.S. and international regulatory authorities.