CytRx Corporation, a biopharmaceutical company specializing in oncology, initiates an international phase II b clinical trial to evaluate the preliminary efficacy and safety of its tumour-targeting doxorubicin conjugate INNO-206 in patients with late-stage soft tissue sarcoma. The phase II b clinical trial will provide the first direct clinical trial comparison of INNO-206 with native doxorubicin, which is dose-limited due to toxicity, as a first-line therapy.

“This trial is the next important step in advancing the development of INNO-206 and follows encouraging response and safety indications from the group of patients with advanced solid tumours, principally soft tissue sarcomas, in the phase I b/2 clinical trial,” said CytRx president and CEO Steven A Kriegsman. “We are addressing an unmet medical need as patients with late-stage sarcomas have a poor prognosis, with progression-free survival of around four to five months and median overall survival averaging approximately 15 months.”

Daniel Levitt, MD, PhD, chief medical officer at CytRx said, “Several chemotherapy regimens have been explored as palliative therapy for patients with advanced soft tissue sarcomas, with combinations of ifosfamide and doxorubicin appearing to offer the highest response rates and longest time to progression. However, these regimens are quite toxic, especially for older patients, and have not significantly increased survival in these individuals. INNO-206 may represent a significant improvement over doxorubicin, as INNO-206, with its tumour-targeting linker, allows us to deliver a doxorubicin dose equivalent of 3½ times the standard doxorubicin dose administered to sarcoma patients without any apparent increased toxicity. Because doxorubicin should be released from INNO-206 at the site of the tumour due to its acid-sensitive linker, higher concentrations of this lethal drug can accumulate within the malignant cells.”

The phase II b clinical trial with INNO-206 in patients with soft tissue sarcomas is an international trial under the direction of world-renowned expert in soft tissue sarcoma treatment Sant P Chawla, MD, F R A C P, director of the Sarcoma Oncology Centre in Santa Monica, California. Dr Chawla also is acting as principal investigator for the Company’s ongoing phase I b/II clinical trial with INNO-206.

The phase IIb clinical trial’s primary objectives are to measure the progression-free survival, tumour response and overall survival of patients with advanced soft tissue sarcomas treated with INNO-206. This clinical trial also will assess the safety of INNO-206 compared to doxorubicin in this patient population through a number of indicators, including the frequency and severity of adverse events. The open-label trial will enroll 105 patients with metastatic, locally advanced or unresectable soft tissue sarcoma at approximately 30 study centres in the US, Hungary, Romania, Ukraine, Russia, India and Australia. Patients will be randomized into two groups with twice as many receiving INNO-206 as doxorubicin. Patients will be treated intravenously once every 21 days for up to eight consecutive cycles with INNO-206 administered drug at 350 mg/m2 (260 mg/m2 doxorubicin equivalents) and doxorubicin administered at 75 mg/m2 .

INNO-206 is a novel conjugate of doxorubicin that binds covalently to albumin, the most abundant protein in blood plasma, and is circulated throughout the body. Doxorubicin is a standard chemotherapeutic treatment for a variety of cancers and is used either alone or in combination with other chemotherapy agents. INNO-206 is designed with a linker that releases doxorubicin in the low pH environment of tumours, concentrating the chemotherapeutic agent where it preferentially damages the tumour while minimizing the effect on healthy tissues. This conjugate formulation has the potential to safely deliver greater amounts of doxorubicin directly to the tumour compared with standard doxorubicin treatment, which could lead to improved efficacy.

CytRx holds the exclusive worldwide rights to INNO-206 – a platform technology designed to reduce adverse events by controlling drug release and preferentially targeting tumours. In addition to doxorubicin, several other chemotherapy agents have been attached to the linker used for INNO-206, including paclitaxel, cisplatin and methotrexate, and may be incorporated into future clinical development by CytRx.

CytRx Corporation is a biopharmaceutical research and development oncology company engaged in the development of high-value human therapeutics. The CytRx oncology pipeline includes three programs in clinical development for cancer indications: INNO-206, tamibarotene and bafetinib.