ZIOPHARM Oncology, Inc. (Nasdaq: ZIOP), a drug development company employing small molecule and synthetic biology approaches to cancer therapy, announced today promising clinical results from an ongoing multicenter Phase 1b, open-label, dose escalation study of intravenous (IV) palifosfamide (Zymafos ® or ZIO-201) in combination with etoposide and carboplatin in patients with small cell lung cancer (SCLC) and other selected cancers. The data are being presented at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, being held November 12-16, in San Francisco.

Palifosfamide is a novel DNA cross-linker in class with bendamustine, ifosfamide, and cyclophosphamide. The ongoing Phase 1b study was designed to assess the safety and efficacy of palifosfamide in combination with carboplatin and etoposide (PaCE) in SCLC and other cancers in which carboplatin plus etoposide is considered an appropriate therapeutic option. A previous randomized study evaluating the addition of ifosfamide to cisplatin and etoposide in SCLC demonstrated improved survival, but with a disabling increase in toxicity with the combination. The rationale for substituting palifosfamide for ifosfamide in this three-drug regimen includes the abrogation of ifosfamide-metabolite related toxicities, an ability to increase the dose delivered over time, and avoiding resistance mediated by aldehyde dehydrogenase (ALDH) overexpression. ALDH overexpression is associated with cancer cell stem-like potential in several tumor types and is thought to confer resistance to ifosfamide and cyclophosphamide.

A total of 22 patients (11 females and 11 males) have been treated to date in the study: 7 with SCLC, 3 with non-SCLC, 3 with ovarian cancer, 1 with germ cell tumor and 8 with other cancers. The maximum tolerated dose of palifosfamide was determined to be 130 mg/m 2 when administered in combination with etoposide (90 mg/m 2 with an additional cohort ongoing at 100 mg/m 2) and carboplatin (AUC4). The dose limiting toxicity was neutropenic fever.

Of the 22 patients, 13 are evaluable for efficacy. Seven are not yet evaluable for response and 2 patients did not continue beyond cycle 1 due to an adverse event. Among the 13 patients evaluable for efficacy, there were 5 patients with partial responses (PR), 4 with stable disease (SD), and 4 with progressive disease (PD). Of the 4 patients with SCLC, 2 showed PR, 1 SD and 1 PD. Partial responses were also seen in non-SCLC (1), ovarian cancer (1), and germ cell tumor (1).

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