CytRx Corporation, a biopharmaceutical company specializing in oncology, announced the achievement of complete remissions in aggressively growing in vivo ovarian cancer tumours treated with a combination of low doses of CytRx's tumour-targeted albumin-binding doxorubicin conjugate INNO-206 and the commonly prescribed cancer treatment doxorubicin.

The study evaluated the anti-tumour efficacy of INNO-206 in an ovarian xenograft cancer model in animals, alone and in comparison to doxorubicin, each at their respective Maximum Tolerated Doses (MTDs) and in combination at half of their respective MTDs. Doxorubicin at its optimal dose showed only a moderate effect in the animal model. In contrast, INNO-206 at its optimal dose induced complete remissions, and the increased effectiveness was statistically significant compared to the doxorubicin-treated group. Administering either drug by itself resulted in significant body weight loss; however, weight loss was significantly reduced when the drugs were given in combination at the lower doses.

The results were published on-line ahead of print in the original article, “Combination therapy with albumin-binding prodrug of doxorubicin (INNO-206) and doxorubicin achieves complete remissions and improved tolerability in an ovarian A2780 xenograft model,” in the peer-reviewed journal Investigational New Drugs (http://www.springerlink.com/content/v4286257326571wm).

Steven Kriegsman, CytRx's president and CEO, said, “This trial exemplifies the importance of our on-going relationship with the inventor of INNO-206, Dr Felix Kratz, Head of the Division of Macromolecular Prodrugs at the Tumour Biology Centre in Freiburg, Germany. We are excited about the progress with INNO-206 and are looking forward to reporting our phase I b clinical trial results in soft tissue sarcomas in the coming months.”

“The achievement of complete remissions in this aggressively growing tumor model is notable,” said Felix Kratz, PhD. “We were indeed surprised that our experimental design demonstrated that the combination of INNO-206 and doxorubicin at lower doses achieved complete tumour remissions combined with the best tolerability. Previous experience in other animal model tumours have shown no or only moderate tumour inhibition with lower doses of INNO-206 or doxorubicin administered as single agents.

“The most likely explanation for the combination therapy's superior results is due to the different and complementary tumour distribution patterns of the two doxorubicin formulations. Indeed, very recently we have obtained complete remissions with an optimized combination schedule of INNO-206 and doxorubicin without any signs of body weight loss in a pancreatic xenograft model which essentially does not respond to conventional chemotherapy at all. These results open a new avenue of combining both drugs at higher doses against resistant or refractory tumours,” he added. “We will report on our new results in the next few months.”

Daniel Levitt, MD, PhD, chief medical officer at CytRx said, “Due to the heterogeneous nature of cancer tumours, we expect that cancer treatment in the future will increasingly become more personalized and include combinations of therapies, rather than a monotherapeutic approach. The fact that INNO-206 in a combination therapy was able to achieve complete remissions while lowering the dose level of both agents has the potential to reduce toxicity and improve tolerability.”

CytRx holds the exclusive worldwide rights to INNO-206, a tumour-targeted doxorubicin conjugate. INNO-206 was designed to reduce adverse events by controlling drug release and preferentially targeting solid tumours. The Company recently announced the safe delivery of INNO-206 at doses more than 4-times higher than the standard doxorubicin dose in its open-label phase I b safety and dose escalation clinical trial in soft tissue sarcomas with INNO-206.

CytRx plans to initiate a phase II b clinical trial as a treatment for soft tissue sarcomas in 2011, following the phase I b dose escalation safety trial. Previous studies have shown INNO-206 efficacy in tumour models of breast, ovarian, small cell lung cancer, renal cell cancer and pancreatic cancers. Several other chemotherapy agents have been attached to the linker used for INNO-206, including paclitaxel, camptothecin, cisplatin and methotrexate, and may be incorporated into future clinical development by the Company.