CuraGen presents encouraging results from ongoing Phase I / II study of CR011-vcMMAE in metastatic melanoma

Clinical-stage biopharmaceutical company CuraGen Corporation has presented encouraging results from the ongoing Phase I/II study of CR011-vcMMAE for the treatment of unresectable Stage III or Stage IV melanoma. This Phase II trial is evaluating the safety and efficacy of CR011-vcMMAE for patients with unresectable Stage III or Stage IV melanoma who have failed no more than one prior line of cytotoxic therapy.

The results were presented by Dr Patrick Hwu, co-principal investigator, and professor, chairman, department of Melanoma Medical Oncology at The University of Texas, MD Anderson Cancer Centre.

"In this heavily pretreated group of patients with primarily Stage IV disease, the observation of dose-dependent objective responses, tumor shrinkage, and encouraging early progression-free rate at 12 weeks at doses in the anticipated active range, leads us to believe that CR011-vcMMAE could be a potentially useful treatment for patients with advanced melanoma," commented Dr. Timothy Shannon, president and chief executive officer of CuraGen Corporation.

"Based on these promising results in melanoma we have expanded the CR011-vcMMAE development program to include a Phase II trial in metastatic breast cancer, and are also exploring additional doses and schedules to further optimize the activity of this antibody-drug conjugate."

As of 4 April 2008, 40 patients were treated in this first-in-man Phase I/II study including a total of 32 patients in the Phase I dose-escalation portion of the trial that aimed to identify the safety and maximum tolerated dose (MTD) of CR011-vcMMAE and eight patients in the ongoing Phase II portion of the study. During Phase I, doses of CR011-vcMMAE between 0.03 mg/kg to 2.63 mg/kg were evaluated and generally well tolerated, with rash and neutropenia emerging at higher doses. A total of 130 treatment cycles were administered (range 2 - 19+ cycles per patient). Two dose-limiting toxicities, consisting of rash, were reported at the highest dose evaluated, and therefore the per-protocol MTD was determined to be 1.88 mg / kg administered intravenously (IV) once every three weeks.

Over 80 per cent of the patients treated had Stage IV disease and had received a median of 2 prior therapies (range 0 - 6). A total of 37 patients from both Phase I and the ongoing Phase II were evaluable for tumor response by RECIST criteria. The activity of CR011-vcMMAE was dose dependent with 50 per cent of those patients treated with doses at or above 1.34 mg / kg exhibiting tumour shrinkage and 64 per cent progression-free at 12 weeks compared to 17 per cent with tumor shrinkage seen and 28 per cent progression-free at 12 weeks for patients treated at lower doses.

In the Phase I portion of the study, 13 evaluable patients were treated with doses at or above 1.34 mg/kg of which one confirmed partial response and six patients with stable disease were reported. In the Phase II portion of the study evaluating CR011-vcMMAE 1.88 mg/kg, there were six evaluable patients of which one partial response (confirmatory visit pending at time of presentation) and three patients with stable disease were reported.

"The overexpression of the GPNMB protein by melanoma makes it an intriguing and novel therapeutic target. The antibodydrug conjugate CR011-vcMMAE, which targets GPNMB, has shown some encouraging activity in this ongoing study, and we look forward to continuing to explore the potential of this drug in this patient population in need of new therapies," commented Dr Hwu.

In addition to M D Anderson Cancer Centre, other study sites in the melanoma trial include Yale Cancer Centre, New Haven, CT; The Angeles Clinic and Research Institute, Santa Monica, CA; and New York University Medical Center, New York, NY.

About CR011-vcMMAE: CR011-vcMMAE is an antibody-drug conjugate (ADC) being developed by CuraGen that consists of a fully-human monoclonal antibody, CR011, linked to a potent cell-killing drug, monomethyl-auristatin E (MMAE). The ADC technology, comprised of MMAE and a stable linker system for attaching it to CR011, was licensed from Seattle Genetics, Inc.

The ADC is designed to be stable in the bloodstream. Following intravenous administration, CR011-vcMMAE targets and binds to GPNMB, a specific protein that is predominantly expressed on the surface of cancer cells, including melanoma, breast cancer and gliomas. Upon internalization into the targeted cell, CR011-vcMMAE is designed to release MMAE from CR011 to produce a cell-killing effect. Preclinical studies conducted with this potential therapeutic demonstrate that CR011-vcMMAE produces strong, reproducible and durable effects against tumors in animal models of human cancer. CR011-vcMMAE is currently in a Phase II trial assessing the safety and efficacy in the treatment of melanoma and will enter Phase II during the third quarter of 2008 for the treatment of metastatic breast cancer.

About Melanoma: Melanoma is a very serious form of skin cancer that accounts for the majority of skin-cancer related deaths each year. The number of people diagnosed with melanoma is rapidly increasing with more than 62,000 new cases expected to be diagnosed in the US during 2008. While the chance of developing melanoma increases with age, it remains one of the most common cancers in young adults. This type of cancer begins in specific cells in the skin and can metastasise, or spread, throughout the body to many organ systems. Patients with Stage IV metastatic melanoma typically have a median survival of less than nine months despite current standard therapies, underscoring the need for novel therapeutics to address the unmet medical need in this patient population.