Full Press Release Details
Provides Guidance on Planned Pivotal Phase III Study
Palifosfamide in Metastatic Soft Tissue Sarcoma
New York, NY - June 21, 2010 -
ZIOPHARM Oncology, Inc. (Nasdaq: ZIOP) announced guidance today regarding the
Company's planned pivotal Phase III trial for palifosfamide in metastatic soft
tissue sarcoma, including details of the proposed study's design, timing and
reporting of favorable interim results from its Phase II randomized controlled
trial of palifosfamide plus doxorubicin vs. doxorubicin in patients with
metastatic or unresectable soft tissue sarcoma (PICASSO), the Company obtained
input on the protocol design for a pivotal Phase III trial from the U.S. Food
and Drug Administration (FDA) in an end of Phase II meeting in January. In that
meeting, the Company also discussed its intention to seek Special Protocol
Assessment (SPA) in which the Company is currently engaged.
Company has proposed that the pivotal trial, known as PICASSO III, be based upon
PICASSO. The Company recently presented additional results from the PICASSO
study at the 46th Annual American Society of Clinical Oncology Meeting. The
additional results for the primary endpoint, progression-free survival (PFS),
demonstrated that, in 62 evaluable patients, a hazard ratio of 0.43 favoring the
palifosfamide combination (p=0.019) was achieved, along with a clinically
meaningful 3.4 month difference in median PFS. For patients receiving 6 cycles
or less in both arms (the standard treatment period for doxorubicin), the hazard
ratio was 0.39 (p= 0.023). Updated safety data showed there was similarity
between the arms of the study. The most common grade 3+ events were neutropenia
and elevated creatinine and were observed with similar frequency between
treatment groups. There was no encephalopathy, hemorrhagic cystitis, or
designed, the Company's PICASSO III study is a randomized, double-blinded,
placebo-controlled, pivotal Phase III trial. Patients with metastatic soft
tissue sarcoma in the front-line setting will be randomized either to
doxorubicin plus placebo or to doxorubicin in combination with palifosfamide.
Progression-free survival is designated as the primary endpoint for accelerated
approval, while overall survival is the primary endpoint for full
recent communication, FDA has indicated that the Company could conduct the
pivotal trial as designed without SPA and that approvability would be determined
by the data, balanced with risks and benefits. FDA presently considers the
endpoints as designated for the proposed pivotal trial as not supportive of SPA
in this disease setting, although they would grant SPA with modified endpoints.
The Company intends to request a meeting with FDA, regarding the proposed
designation of study endpoints while it weighs the advisability of moving
forward with the current design. Therefore the Company expects enrollment in
PICASSO III to begin in the third quarter rather than this month, as previously
ZIOPHARM Oncology, Inc.:
Oncology is a biopharmaceutical company engaged in the development and
commercialization of a diverse portfolio of cancer drugs. The Company is
currently focused on three clinical programs.
(ZymafosTM or ZIO-201) references a novel composition (tris formulation) that
comprises the functional active metabolite of ifosfamide, a standard of care for
treating sarcoma, lymphoma, testicular, and other cancers. Palifosfamide
delivers only the cancer fighting component of ifosfamide. It is expected to
overcome the resistance seen with ifosfamide and cyclophosphamide, two of the
most commonly used DNA-alkylating drugs used to treat cancers. Palifosfamide
does not have the toxic metabolites of ifosfamide that cause the debilitating
side effects of "fuzzy brain" (encephalopathy) and severe bladder inflammation.
It may also have other advantages. Intravenous palifosfamide is currently in a
randomized Phase II trial to treat unresectable or metastatic soft tissue
sarcoma in the front- and second-line setting with the Company having reported
interim positive results at the 2010 ASCO Annual Meeting; a registration trial
in the same setting is expected to initiate following U.S. Food and Drug
Administration (FDA) review. An oral form of palifosfamide has been developed
preclinically to the investigational new drug application stage.
(ZinaparTM or ZIO-101) is a novel mitochondrial-targeted agent (organic arsenic)
being developed for the treatment of various hematologic and solid cancers.
Preclinical and clinical studies to date have demonstrated that darinaparsin is
considerably less toxic than inorganic arsenic, particularly with regard to
cardiac toxicity. The Company has reported favorable results from a Phase II
trial with IV-administered darinaparsin in lymphoma, particularly peripheral
T-cell lymphoma ("PTCL"), at the American Society of Clinical Oncology (ASCO) in
May of 2009 which would serve as the basis for ongoing clinical study in PTCL
following regulatory review and available financial resources. Phase I trials
with the oral form are ongoing in both hematological malignancies and solid
(ZybulinTM or ZIO-301) is a novel, oral tubulin binding agent that targets both
mitosis and cancer cell migration. In addition, indibulin is expected to have
several potential benefits, including oral dosing, application in multi-drug
resistant tumors, no neuropathy and minimal overall toxicity. In multiple Phase
I trials in cancer patients, oral indibulin has been administered both as a
single agent and in combination with favorable activity and a promising safety
profile that does not include the neurotoxicity seen with all of the other
classes of tubulin binding agents. Most recently, results of oral indibulin in
combination with oral capecitabine (Xeloda(R)) were presented at last year's
American Society of Clinical Oncology (ASCO) along with the preclinical findings
of a novel dosing schedule conducted under the direction of Dr. Larry Norton;
employing this dosage schedule, the Company has initiated a Phase I study in
breast cancer patients with the Breast Cancer Medicine Service at Memorial
Sloan-Kettering Cancer Center.
operations are located in Boston, MA with an executive office in New York City.
Further information about ZIOPHARM may be found at
Safe Harbor Statement:
press release contains forward-looking statements for ZIOPHARM Oncology, Inc.
that involve risks and uncertainties that could cause the Company's actual
results to differ materially from the anticipated results and expectations
expressed in these forward-looking statements. These statements are based on
current expectations, forecasts and assumptions that are subject to risks and
uncertainties, which could cause actual outcomes and results to differ
materially from these statements. Among other things, there can be no assurance
that any of the Company's development efforts relating to its product candidates
will be successful, or such product candidates will be successfully
commercialized. Other risks that affect forward-looking information contained in
this press release include the possibility of being unable to obtain regulatory
approval of the Company's product candidates, the risk that final trial data may
not support interim analysis and that the results of clinical trials in general
may not support the Company's claims, the risk that pre-clinical or clinical