CuraGen Announces Preliminary Data from Ongoing Phase II Study Showing Clinical Activity of CR011-vcMMAE in Patients with Metastatic Melanoma
BRANFORD, Conn., Nov. 3 /PRNewswire-FirstCall/ -- CuraGen Corporation announced today preliminary data from an ongoing Phase II trial of CR011-vcMMAE, an antibody-drug conjugate that targets GPNMB, for the treatment of patients with unresectable Stage III or Stage IV melanoma. Dr. Patrick Hwu, Co-Principal Investigator, and Professor and Chairman of the Department of Melanoma Medical Oncology, at The M. D. Anderson Cancer Center, presented the data during an oral session at the 2008 International Society for Biologic Therapy of Cancer (iSBTc) Annual Meeting.
Thirty-six patients were enrolled into this Phase II open-label, multi-center trial that is evaluating the efficacy and safety of CR011-vcMMAE 1.88 mg/kg administered intravenously once every three weeks. Eligible patients had progressive disease at trial entry and may have received one prior cytotoxic regimen and any number of prior immunotherapies. Of the patients enrolled, 94% had Stage IV disease of which two-thirds were classified as M1c, the poorest risk group.
At the time of the data cutoff for this analysis (19 Sept 2008), 31 patients had at least one efficacy assessment available, and 18 patients were continuing to receive ongoing treatment in the study. The median overall progression-free survival (PFS) to date was approximately 4.5 months. RECIST-defined partial responses were reported in 3 patients, 2 ongoing, and an unconfirmed partial response in 1 patient. Nineteen patients had stable disease, 14 ongoing, with tumor shrinkage observed in 12 of these patients.
"PFS is a clinically meaningful and important regulatory endpoint. The apparent prolongation in PFS of 4.5 months, compared to a historical expectation of 1.7 months, combined with clear objective responses and tumor reduction in the majority of patients, suggests that CR011-vcMMAE has the potential to become an important novel therapy in this patient population," commented Dr. Timothy Shannon, President and Chief Executive Officer of CuraGen.
As expected based upon the expression of GPNMB and as observed in Phase I, dermatologic adverse events consisting of rash, alopecia, and pruritus were the most common toxicities in this study. A preliminary exploratory analysis assessing the relationship of rash and PFS was performed and showed a trend toward longer PFS in patients that developed Grade 2 or higher rash (n=13). Other adverse events included fatigue, diarrhea, anorexia and nausea. Grade 3 or 4 neutropenia was observed in 7 patients (22%).
"The target of CR011-vcMMAE, GPNMB, is a protein that is believed to be over expressed in a variety of tumors and also present in some normal tissue including the skin. The preliminary data which may suggest a correlation between the development of rash and clinical efficacy is very intriguing and we will continue to assess its potential role in helping to identify those patients who may best respond to treatment with CR011-vcMMAE," commented Dr. Ronit Simantov, Chief Medical Officer at CuraGen. "We would like to thank our investigators for their enthusiasm, which we believe is highlighted by their ability to fully enroll this Phase II trial in just 6 months, and we look forward to reporting the final data from this Phase II trial during the first half of 2009."
"Targeting GPNMB with this antibody-drug conjugate represents a potentially novel way to treat this disease, and based on these preliminary Phase II results, CR011-vcMMAE appears to be clinically active against unresectable melanoma in some patients. We look forward to further evaluating the correlation between rash and clinical activity, as well as alternate dosing schedules of CR011-vcMMAE," commented Dr. Hwu.
CuraGen is currently enrolling patients into a Phase I portion of this trial to evaluate more frequent dosing schedules of CR011-vcMMAE, including a weekly and a two out of every three-week regimen, to explore if more frequent administration can provide additional activity in patients with metastatic melanoma. CR011-vcMMAE is also being studied in an ongoing Phase II trial in patients with metastatic breast cancer who have received previous chemotherapy. CuraGen anticipates providing updated data from the ongoing melanoma and breast cancer studies in the first half of 2009.
"While we continue to finalize data from this study, develop data from more frequent dosing in patients with metastatic melanoma and from the Phase II study in patients with breast cancer, we will be engaging in discussions with potential partners as we develop plans for the advanced stages of development," added Dr. Shannon. "The goal of a partnership will be to support the financial, development and commercial resources that will be required in advanced development, improving the risk profile to CuraGen shareholders while maintaining upside potential."
In addition to M. D. Anderson, other sites participating in the melanoma trial include Yale Cancer Center, New Haven, CT; The Angeles Clinic and Research Institute, Santa Monica, CA; and Medical Center, New York, NY.
Conference Call Details and Dial-in Information Date: Monday, November 03, 2008, 2008 Time: 11:00 a.m. EDT Dial-in: 877-272-5391 (domestic) 706-758-4315 (international) Passcode: 71190212 Webcast: Access available at http://www.curagen.com
A replay of the conference call will be available starting at 2:00 p.m. Eastern time on Monday, November 3, 2008 through Wednesday, December 3, 2008 by dialing 800-642-1687 (domestic) or 706-645-9291 (international). The passcode for the replay is 71190212. An archive of the webcast will be available for 30 days at http://www.curagen.com.
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. CR011-vcMMAE is currently in two Phase II trials assessing the safety and efficacy in the treatment of melanoma and for the treatment of metastatic breast cancer, and in a Phase I trial to evaluate the safety and activity of alternate dosing schedules.
According to the American Cancer Society, it is expected that approximately 60,000 new cases of melanoma will be diagnosed, including nearly 11,000 patients diagnosed with Stage III or Stage IV disease, and an estimated 8,000 people in the U.S. will die of the disease during 2008. The prognosis for patients with advanced melanoma is poor, and studies have shown that the median survival is less than nine months.
CuraGen Corporation is a clinical-stage biopharmaceutical company developing promising approaches for the treatment of cancer. CuraGen Corporation is headquartered in Branford, Connecticut. For additional information please visit http://www.curagen.com.
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Posted: November 2008