ZIOPHARM Doses First Patient in Phase III Cancer Study

ZIOPHARM Oncology, Inc. recently announced that the first patient has been dosed in the MATISSE study (Multicenter Adaptive Trial Investigating Small cell lung cancer Survival Endpoints), a pivotal Phase III multi-center, open-label, adaptive, randomized study of palifosfamide for the treatment of small cell lung cancer. ZIOPHARM has also recently announced the completion of enrollment in its Phase III study of palifosfamide in combination with doxorubicin for the treatment of metastatic soft tissue sarcoma in the front-line setting (PICASSO 3).

The MATISSE study is designed to enroll up to 548 chemotherapy naive patients with extensive-stage small cell lung cancer. Eligible patients will be randomized, one-to-one, to receive either palifosfamide in combination with carboplatin and etoposide (PaCE) or carboplatin and etoposide alone. The trial’s primary endpoint is overall survival.

Secondary endpoints include progression-free survival, objective response rate, and quality of life. MATISSE will be conducted at centers in North America, Europe, Australia, and Asia.

“Small cell lung cancer is an extraordinarily difficult-to-treat cancer, for which there has been no novel treatment in decades,” said 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 a member of ZIOPHARM’s Medical Advisory Board. “An important element of treating the disease is to find an agent that is safe and has minimal variability between patients. Palifosfamide has demonstrated broad therapeutic activity, including effects against cancer stem cells, as well as good tolerability alone and in combination with various chemotherapeutics.

MATISSE incorporates a novel, adaptive study design that should provide a clinically meaningful understanding of palifosfamide’s activity and tolerability in advanced disease as quickly as possible for this heavily underserved population.”

The study’s adaptive design includes a prospectively planned opportunity for modification of the study protocol by adjusting one or more specified components of the design in order to maintain adequate power. Evaluation of the study’s powering will be conducted by an Independent Data Monitoring Committee (IDMC) at a single, pre-planned interim analysis, scheduled to occur following 125 events. At the interim analysis, the IDMC will review all efficacy and safety data and decide whether to: 1) halt the study for efficacy or futility, 2) continue the study to its planned enrollment of 548 patients, 3) decrease sample size, or 4) increase event size.

The MATISSE study is designed around clinical data from several studies of palifosfamide, including a Phase Ib, open-label, dose escalation study of intravenous palifosfamide in combination with etoposide and carboplatin in patients with SCLC and other selected cancers, which demonstrated good tolerability and a clinical benefit rate of 67%. Data from a Phase III randomized study of ifosfamide, an in-class DNA-targeted anti-cancer therapy, conducted by the Hoosier Oncology Group (HOG) were also incorporated in to the efficacy rationale for the MATISSE study.

In this HOG study, ifosfamide demonstrated a survival benefit, the only front-line therapy added to standard of care to do so in SCLC, but was not pursued due to the excessive toxicities.

ZIOPHARM Oncology is a biopharmaceutical company focused on the development and commercialization of new cancer therapies. The company’s clinical programs include:

Palifosfamide (ZIO-201), a novel DNA-targeted cancer treatment that bypasses drug resistance mediated by ALDH (aldehyde dehydrogenase), an enzyme associated with cancer stem cells, and has a favorable toxicity profile. Intravenous palifosfamide is currently being studied in a randomized, double-blinded, placebo-controlled Phase III trial (PICASSO 3) for the treatment of front-line metastatic soft tissue sarcoma and is also in a pivotal Phase III trial (MATISSE) for front-line metastatic small cell lung cancer. Additionally, the company is developing an oral capsule form of palifosfamide.

IL-12 DNA, a novel DNA therapeutic that is delivered to the patient’s tumor and expresses interleukin-12, a protein that controls anti-cancer immune responses. IL-12 DNA is currently in two Phase I studies, with plans to move into Phase II studies. ZIOPHARM’s DNA therapeutics are being developed in partnership with Intrexon Corporation through a revolutionary synthetic biology platform that allows for targeted, controlled production of therapies in humans with a biologic on/off switch (the RheoSwitch Therapeutic System. Preclinical and discovery work with multiple therapeutic approaches, such as antibodies, immunotoxins, and protein decoys, is expected to result in multiple clinical candidates in the next 12 to 24 months.

Indibulin (ZIO-301) is a novel, tubulin binding agent that is expected to have several potential benefits, including oral dosing, application in multi-drug resistant tumors, no neuropathy and a tolerable toxicity profile. It is currently being studied in a Phase I/II trial in metastatic breast cancer.

Darinaparsin (ZIO-101) is a novel mitochondrial- and hedgehog-targeted agent (organic arsenic) currently in ongoing studies with Solasia Pharma K.K.

For more information, visit www.ziopharm.com.