At the 40th Annual Meeting of the American Society of Clinical Oncology, Cell Therapeutics Inc (CTI) presented preliminary phase I data on a novel polyglutamate camptothecin, known as CT-2106.
The objectives of the multicenter, open-label study are to determine the maximum tolerated dose (MTD) and to evaluate the tolerability, safety and pharmacokinetics of CT-2106 when administered to patients with advanced malignancies. Patients received a median of three prior regimens (range 1-4).
The data showed that CT-2106 was well tolerated and lacked the severe gastrointestinal (diarrhea) and bladder (hematuria) toxicities, which are typical for camptothecins. The dose limiting side effects were neutropenia and thrombocytopenia. Twenty-six per cent of patients achieved disease control. One patient with pancreatic cancer, that had spread to the lungs, exhibited a partial response, another pancreatic patient achieved disease control, two patients with colorectal cancer had stable disease for more than three months, and four patients with non-small cell lung cancer achieved stable disease, two of those patients experienced disease control for almost nine months. The MTD of CT-2106 administered every third week has been determined to be 75mg/m2.
"The results of this phase I trial support the finding that our polyglutamate technology can significantly modify the severe side effects of another important class of chemotherapy drugs, the camptothecins, while retaining their potent anti-tumor activity. The dose limiting toxicity was short-lived and predictable marrow suppression," noted Jack W. Singer, chief medical officer at CTI. We have initiated a phase II study in colorectal cancer and expect to initiate phase II trials in ovarian and small cell lung cancer later this year," he added.
CT-2106 is the second agent in CTI's portfolio, after Xyotax (paclitaxel poliglumex), to exploit the polyglutamate-conjugate technology, where an anti-cancer agent is conjugated to a naturally biodegradable poly-amino acid. The clinical experience with Xyotax, which is completing enrollment in multiple phase III trials for non-small cell lung cancer, further confirms CTI's preclinical work, which has shown that the polyglutamate technology has the ability to eliminate the need for toxic solubilizing agents and decrease the amount of drug exposure in normal tissues while increasing the amount of drug reaching tumor tissues.
Camptothecins are one of the world's fastest growing classes of anti-cancer agents and are commonly used as treatment for colorectal, lung and ovarian cancer, however they are limited by severe side effects.