BOSTON, MA, USA I June 1, 2013 I ZIOPHARM Oncology, Inc. (ZIOP) today announced updated results from the Phase 1 study in advanced melanoma using Ad-RTS-IL-12, a novel DNA-based therapeutic candidate. Findings were presented in a poster presentation at the 2013 American Society for Clinical Oncology (ASCO) Annual Meeting being held May 31 — June 4, 2013 at McCormick Place in Chicago, IL. A presentation of the poster, titled “A phase I open-label study of Αd-RTS-hIL-12, an adenoviral vector engineered to express hIL-12 under the control of an oral activator ligand, in subjects with unresectable stage III/IV melanoma,” was delivered by Gerald P. Linette, MD, PhD, Associate Professor, Medicine and Neurosurgery, Division of Oncology, at the Washington University School of Medicine.
For the study, Ad-RTS-IL-12, an adenoviral vector engineered to express IL-12 utilizing the RheoSwitch Therapeutic System(R) (RTS(R)) technology, was injected intratumorally in patients with advanced melanoma (n=14). Expression of IL-12 was controlled through the administration of an oral activator ligand (INXN-1001), which was administered in four ascending dose cohorts. The Company previously reported that compelling clinical activity was observed in five of seven (71 percent) patients dosed at the two highest dose levels (Nemunaitis et al. ASGCT 2013). The study further demonstrated that treatment with Ad-RTS-IL-12 + INXN-1001 was shown to increase intratumoral IL-12 mRNA transcription. The mRNA level was very tightly controlled (on and off) by the biologic switch and oral activator ligand. Consequent on the increase in IL-12 expression there was a major increase in tumor-infiltrating lymphocytes (CD8+, CD45RO+) in the tumor microenvironment as measured in tumor biopsies. Subsequently clinical activity was observed in injected and non-injected lesions, primarily at the higher doses of INXN-1001 (100 and 160 mg), with inflammation, shrinkage, flattening, and depigmentation of lesions correlated with the highest serum levels of IFN-γ.
ZIOPHARM is currently conducting a Phase 2 multi-center, single-arm, open-label expansion study in up to 15 patients with unresectable Stage III or IV melanoma. The Phase 2 study will focus on optimization of the dosing schedule, guided by pharmacokinetics and tolerability, using every other day dosing of the oral activator ligand.
“The promise of immune stimulation in cancer treatment is now at the leading edge of oncology research, with Ad-RTS-IL-12, as a potent and highly controllable immune stimulator, demonstrating meaningful potential in this field,” said Dr. Linette. “Being able to regulate the expression of IL-12 through a gene therapy strategy provides for the ability to optimize response and tolerability in ways that cannot be achieved with recombinant proteins or other drug delivery strategies. We look forward to taking advantage of this ability and our observations in Phase I to optimize the ongoing Phase 2 study of Ad-RTS-IL-12 in advanced melanoma.”
About ZIOPHARM Oncology, Inc.:
ZIOPHARM Oncology is a biopharmaceutical company focused on the development and commercialization of new cancer therapies. The Company’s clinical programs include:
Ad-RTS-IL-12 is currently being tested in two Phase 2 studies, the first for the treatment of advanced melanoma, and the second in combination with palifosfamide for the treatment of non-resectable recurrent or metastatic breast cancer. Ad-RTS-IL-12 uses synthetic biology to enable controlled delivery of therapeutic interleukin-12 (IL-12), a protein important for enhancing the development of an immune response to cancer. In partnership with Intrexon Corporation, ZIOPHARM’s DNA synthetic biology platform employs an inducible gene-delivery system that enables controlled delivery of genes that produce therapeutic proteins to treat cancer. This controlled delivery is achieved by producing IL-12 under the control of Intrexon’s proprietary biological “switch” (the RheoSwitch Therapeutic System(R) or RTS(R) platform) to turn on/off the therapeutic protein expression at the tumor site.
Palifosfamide (ZIO-201) is a potent, bi-functional DNA alkylating agent that has activity in multiple tumors by evading typical resistance pathways. Palifosfamide is in the same class as bendamustine, cyclophosphamide, and ifosfamide. It is currently being studied in an adaptive Phase 3 study in small cell lung cancer. Enrollment in this study was suspended with 188 subjects randomized, and being followed for overall survival. Data is expected in the first half of 2014.
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 1/2 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.
ZIOPHARM’s operations are located in Boston, MA. Further information about ZIOPHARM may be found at www.ziopharm.com.
SOURCE: Ziopharm
Post Views: 123
BOSTON, MA, USA I June 1, 2013 I ZIOPHARM Oncology, Inc. (ZIOP) today announced updated results from the Phase 1 study in advanced melanoma using Ad-RTS-IL-12, a novel DNA-based therapeutic candidate. Findings were presented in a poster presentation at the 2013 American Society for Clinical Oncology (ASCO) Annual Meeting being held May 31 — June 4, 2013 at McCormick Place in Chicago, IL. A presentation of the poster, titled “A phase I open-label study of Αd-RTS-hIL-12, an adenoviral vector engineered to express hIL-12 under the control of an oral activator ligand, in subjects with unresectable stage III/IV melanoma,” was delivered by Gerald P. Linette, MD, PhD, Associate Professor, Medicine and Neurosurgery, Division of Oncology, at the Washington University School of Medicine.
For the study, Ad-RTS-IL-12, an adenoviral vector engineered to express IL-12 utilizing the RheoSwitch Therapeutic System(R) (RTS(R)) technology, was injected intratumorally in patients with advanced melanoma (n=14). Expression of IL-12 was controlled through the administration of an oral activator ligand (INXN-1001), which was administered in four ascending dose cohorts. The Company previously reported that compelling clinical activity was observed in five of seven (71 percent) patients dosed at the two highest dose levels (Nemunaitis et al. ASGCT 2013). The study further demonstrated that treatment with Ad-RTS-IL-12 + INXN-1001 was shown to increase intratumoral IL-12 mRNA transcription. The mRNA level was very tightly controlled (on and off) by the biologic switch and oral activator ligand. Consequent on the increase in IL-12 expression there was a major increase in tumor-infiltrating lymphocytes (CD8+, CD45RO+) in the tumor microenvironment as measured in tumor biopsies. Subsequently clinical activity was observed in injected and non-injected lesions, primarily at the higher doses of INXN-1001 (100 and 160 mg), with inflammation, shrinkage, flattening, and depigmentation of lesions correlated with the highest serum levels of IFN-γ.
ZIOPHARM is currently conducting a Phase 2 multi-center, single-arm, open-label expansion study in up to 15 patients with unresectable Stage III or IV melanoma. The Phase 2 study will focus on optimization of the dosing schedule, guided by pharmacokinetics and tolerability, using every other day dosing of the oral activator ligand.
“The promise of immune stimulation in cancer treatment is now at the leading edge of oncology research, with Ad-RTS-IL-12, as a potent and highly controllable immune stimulator, demonstrating meaningful potential in this field,” said Dr. Linette. “Being able to regulate the expression of IL-12 through a gene therapy strategy provides for the ability to optimize response and tolerability in ways that cannot be achieved with recombinant proteins or other drug delivery strategies. We look forward to taking advantage of this ability and our observations in Phase I to optimize the ongoing Phase 2 study of Ad-RTS-IL-12 in advanced melanoma.”
About ZIOPHARM Oncology, Inc.:
ZIOPHARM Oncology is a biopharmaceutical company focused on the development and commercialization of new cancer therapies. The Company’s clinical programs include:
Ad-RTS-IL-12 is currently being tested in two Phase 2 studies, the first for the treatment of advanced melanoma, and the second in combination with palifosfamide for the treatment of non-resectable recurrent or metastatic breast cancer. Ad-RTS-IL-12 uses synthetic biology to enable controlled delivery of therapeutic interleukin-12 (IL-12), a protein important for enhancing the development of an immune response to cancer. In partnership with Intrexon Corporation, ZIOPHARM’s DNA synthetic biology platform employs an inducible gene-delivery system that enables controlled delivery of genes that produce therapeutic proteins to treat cancer. This controlled delivery is achieved by producing IL-12 under the control of Intrexon’s proprietary biological “switch” (the RheoSwitch Therapeutic System(R) or RTS(R) platform) to turn on/off the therapeutic protein expression at the tumor site.
Palifosfamide (ZIO-201) is a potent, bi-functional DNA alkylating agent that has activity in multiple tumors by evading typical resistance pathways. Palifosfamide is in the same class as bendamustine, cyclophosphamide, and ifosfamide. It is currently being studied in an adaptive Phase 3 study in small cell lung cancer. Enrollment in this study was suspended with 188 subjects randomized, and being followed for overall survival. Data is expected in the first half of 2014.
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 1/2 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.
ZIOPHARM’s operations are located in Boston, MA. Further information about ZIOPHARM may be found at www.ziopharm.com.
SOURCE: Ziopharm
Post Views: 123
