CytRx Corporation a biopharmaceutical company specializing in oncology,  announced that its tumour-targeted doxorubicin conjugate, INNO-206, is delivering doxorubicin safely at doses over 4 times higher than the standard doxorubicin dose in the company's open-label phase I b safety and dose escalation clinical trial. The clinical trial is being conducted in up to 24 patients with advanced solid tumours who have failed standard therapies.

All eight patients treated in the phase I b trial to date were diagnosed with advanced soft tissue sarcomas. Doxorubicin is currently the only FDA-approved drug on the market as a treatment for soft tissue sarcoma and is a standard chemotherapeutic treatment for a variety of other cancers. It is used either alone or in combination with other chemotherapy agents. Dose levels of doxorubicin are limited due to its toxicity. 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. 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.

The phase I b trial is being conducted at the Sarcoma Oncology Centre in Santa Monica, California, under the direction of Sant P Chawla, MD, F.R.A.C.P, a leading expert in sarcomas and sarcoma therapies. “The safety profile of INNO-206 thus far has been impressive,” stated Dr Chawla. “After repeat doses that are more than four-fold higher than the dose of doxorubicin that we use to treat patients with soft tissue sarcomas, side effects have been generally mild and readily reversible. We are continuing treatment and dose escalation in our study." During his tenure at the Sarcoma Oncology Centre, Dr Chawla has studied virtually every important drug being tested to treat soft tissue sarcomas.

“The ability to administer dramatically higher doses of doxorubicin with INNO-206 could represent a major breakthrough in the treatment of various cancers in which doxorubicin is an important component of chemotherapy regimens,” said CytRx president and CEO Steven A. Kriegsman. “Although it is too early in the trial to assess clinical response, we believe that the ability of our conjugate formulation to safely deliver greater amounts of doxorubicin directly to the tumor compared with standard doxorubicin treatment can lead to improved efficacy. We plan to rapidly enter a phase II b clinical trial with INNO-206 in patients with soft tissue sarcomas in the second half of 2011 after completing this dose escalation safety study.”

Patients in the phase I b trial are being administered with INNO-206 at two dose levels: 165 mg/m2 and 260 mg/m2 doxorubicin equivalents. These doses are 2.75 and 4.33 times higher than the standard dose of doxorubicin (60 mg/m2) administered to patients with soft tissue sarcomas. Side effects have been generally mild, with only one patient experiencing grade 3 or 4 neutropenia and thrombocytopenia that resolved without therapy. One patient discontinued INNO-206 due to disease progression after one month, but no patient has discontinued treatment due to toxicity.

CytRx holds the exclusive worldwide rights to INNO-206, which is CytRx's lead compound in its platform technology designed to reduce adverse events by controlling drug release and preferentially targeting tumors. 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 the Company.

Patients with advanced soft tissue sarcomas who can no longer be treated with surgery have a poor prognosis. Progression-free survival for this group is around six to seven months, and median overall survival is approximately 18 months with less than one-third of these patients living past three years. Combinations of the chemotherapy drugs ifosfamide and doxorubicin appear to offer the highest response rates and longest time to progression in these patients; however, these regimens have not significantly improved survival and are quite toxic.