Stabilized IPM

History and Preclinical Development

Palifosfamide (ZIO-201) is a proprietary stabilized metabolite of ifosfamide. Ifosfamide has been shown to be effective in high doses in treating testicular cancer, sarcoma and lymphoma. Ifosfamide-based treatment generally represents the standard of care for sarcoma; however, it is not approved by the FDA in this indication. Ifosfamide metabolites include acrolein and chloroacetaldehyde, both highly toxic.

Preclinical studies have shown that palifosfamide has activity in leukemia and solid tumor cancers. These studies also indicate that palifosfamide has a better safety profile than ifosfamide, likely because the toxic metabolites of ifosfamide, acrolein and chloroacetaldehyde are not present in palifosfamide. We believe the administration of palifosfamide may avoid many of the toxicities of ifosfamide without compromising the activity of the drug.

Lead indication

Advanced sarcoma will be pursued as the lead indication for palifosfamide. It may be a useful agent that can deliver therapeutic activity in patients with advanced sarcoma with fewer side effects than those associated with ifosfamide.

In the U.S., ifosfamide is regularly included in combination regimens (more than one treatment) for the treatment of sarcomas, testicular cancers, head and neck cancer and some types of lymphomas. We believe in the potential for palifosfamide to replace ifosfamide in any or all of these combinations.

Clinical development plan

Palifosfamide is currently in a Phase II randomized controlled trial with doxorubicin in patients with unresectable or metastatic soft-tissue sarcoma (PICASSO trial). A single agent Phase II clinical trial in sarcoma has been completed and awaiting final data, a Phase I soft-tissue sarcoma combination trial with doxorubicin (Adriamycin®) is nearing completion, and an oral study is planned. For more information regarding treatment centers, please visit our clinical trials page.