PRNewswire-FirstCall/ -- CuraGen Corporation reported three data presentations from its ongoing clinical trials of CR011-vcMMAE, an antibody-drug conjugate that targets GPNMB, in patients with advanced breast cancer and melanoma at the 2009 Annual Meeting of the American Society of Clinical Oncology (ASCO) in Orlando, Florida.
The Phase I/II study of CR011-vcMMAE administered intravenously once every three weeks in patients with advanced breast cancer began with a bridging phase to confirm the maximum tolerated dose and has expanded into a Phase II open-label, multi-center study. The study is designed to assess efficacy with an endpoint of progression-free rate at 12 weeks. The principal investigator is Dr. Linda Vahdat, Medical Director of the Breast Cancer Research Program and Associate Professor of Clinical Medicine, NewYork-Presbyterian Hospital/Weill Cornell.
Preliminary data were presented on 18 evaluable patients treated at doses of 1.0 - 1.88mg/kg from the Phase I portion and the initial portion of the Phase II study. Selection for enrollment was not based on expression of GPNMB in patients' tumors. The median number of prior chemotherapy regimens for metastatic disease was 4 (range 2-11). Triple negative disease (ER/PR/Her-2 negative) was present in 44% of patients. Partial responses were seen in 3 patients (1 confirmed), including a patient with triple negative disease. Fifty percent (50%) of patients showed tumor shrinkage. Toxicities were similar to those observed in previous studies with CR011-vcMMAE; the most common adverse events were rash, alopecia, and fatigue. Twelve patients have now been enrolled in the Phase II portion of the study at a dose of 1.88mg/kg given once every three weeks, with total Phase II enrollment planned for up to 25 patients.
"We are very encouraged by the early evidence of activity demonstrated in this trial and look forward to presenting additional data on the Phase II study in the second half of the year," commented Dr. Ronit Simantov, Chief Medical Officer of CuraGen. "The emerging role of GPNMB, which is present in 25-40% of breast cancer patients, combined with our clinical activity, suggests that GPNMB may be an important new target in breast cancer."
Also at ASCO, data from a Phase II trial of CR011-vcMMAE in patients with advanced melanoma were presented at a poster discussion session. Thirty-six patients were enrolled into this Phase II open-label, multi-center trial that evaluated 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.
The study successfully met its primary activity endpoint, with 5 objective responses (1 unconfirmed) observed in 34 evaluable patients, and median duration of response of 5.3 months. The median overall progression-free survival (PFS) was 4.4 months. Tumor shrinkage was observed in 58% of patients, and 20 patients had best response of stable disease. Dermatologic adverse events consisting of rash, alopecia, and pruritus were the most common toxicities in this study. Other adverse events included fatigue, diarrhea, anorexia and nausea. Grade 3 or 4 neutropenia was observed in 5 patients. The absence of rash in the first cycle of treatment predicted a worse PFS. Additionally, in a subset of patients with tumor biopsies, high levels of tumor expression of GPNMB appeared to correlate with favorable outcome.
"These Phase II results show evidence of activity in patients with advanced melanoma that compares favorably to activity seen with other currently used treatments for these patients, who are in need of additional options," commented Dr. Simantov.
In addition, data from the ongoing assessment of more frequent dosing of CR011-vcMMAE in 28 patients with advanced melanoma were presented at ASCO. Thus far, a dose of 1.0 mg/kg given once every week has been identified as the maximum tolerated dose in a weekly schedule, and a dose of 1.5mg/kg is currently being explored in the two out of three week schedule. Although median duration of follow-up is only 6 weeks, objective responses have thus far been observed in 3 of 11 evaluable patients treated with weekly CR011-vcMMAE (1 confirmed) and 1 confirmed response in 8 evaluable patients treated with CR011-vcMMAE two out of every three weeks.
"This study has confirmed that CR011 is active and that more total drug can be safely given with more frequent dosing," stated Dr. Simantov. "The expansion phase of the study will be used to generate a better estimate of the response rate with these schedules to compare to the once every three week schedule."
"The results presented at ASCO are important because they expand the activity of CR011 into patients with metastatic breast cancer and open this area up as an important development opportunity in addition to the opportunity in patients with metastatic melanoma," commented Dr. Timothy Shannon, President and Chief Executive Officer of CuraGen. "The remainder of these studies will be used to better understand the breast cancer opportunity and to understand how dose, schedule and the use of biomarkers such as the presence of GPNMB and rash might be used to enhance activity in further development."
Reprints of the presentation are available on CuraGen's website at http://www.curagen.com or can be requested by emailing email@example.com.
Conference Call Details and Dial-in Information
Date: Wednesday, June 3, 2009
Time: 11:00 a.m. EDT
Dial-in: (877)-856-1956 (U.S. and Canada)
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 Wednesday, June 3, 2009 through Thursday, September 3, 2009 by dialing 888-203-1112 (domestic) or 719-457-0820 (international). The passcode for the replay is 3269449. An archive of the webcast will be available for one year 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 2009. The prognosis for patients with advanced melanoma is poor, and studies have shown that the median survival is less than nine months.
About Breast Cancer
ancer is the most common cancer in women and a leading cause of death in the United States. According to the American Cancer Society, more than 180,000 women will be diagnosed with invasive breast cancer in 2009 with more than 40,000 deaths attributed to this disease. Despite recent advances in therapy, the median survival of patients with metastatic breast cancer is 2 to 3 years, while patients with "triple-negative" or "basal-like" breast cancer have limited treatment options and poorer outcomes. Therefore, a significant unmet need remains for novel therapeutic approaches for patients with locally advanced and metastatic breast cancer who have failed other therapies.
About CuraGenCuraGen Corporation (Nasdaq: CRGN - News) 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.
Statements in this press release regarding management's future expectations, beliefs, intentions, goals, strategies, plans or prospects, including statements relating to CuraGen's development program for CR011-vcMMAE, including CuraGen's ability to advance CR011-vcMMAE through Phase II clinical trials for melanoma and metastatic breast cancer, to explore additional doses and schedules of this antibody-drug conjugate, and to explore the potential of CR011-vcMMAE in a patient population in need of new therapies may constitute forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements can be identified by terminology such as "anticipate," "believe," "could," "could increase the likelihood," "estimate," "expect," "intend," "is planned," "may," "should," "will," "will enable," "would be expected," "look forward," "may provide," "would" or similar terms, variations of such terms or the negative of those terms. Such forward-looking statements involve known and unknown risks, uncertainties and other factors including the risk that any one or more of CuraGen's drug development programs will not proceed as planned for technical, scientific or commercial reasons or due to patient enrollment issues or based on new information from nonclinical or clinical studies or from other sources, the success of competing products and technologies, CuraGen's stage of development as a biopharmaceutical company, government regulation and healthcare reform, technological uncertainty and product development risks, product liability exposure, uncertainty of additional funding, CuraGen's history of incurring losses and the uncertainty of achieving profitability, reliance on research collaborations and strategic alliances, competition, patent infringement claims against CuraGen's products, processes and technologies, CuraGen's ability to protect its patents and proprietary rights and uncertainties relating to commercialization rights, as well as those risks, uncertainties and factors referred to in CuraGen's Quarterly Report on Form 10-Q for the period ended March 31, 2009 filed with the Securities and Exchange Commission under the section "Risk Factors," as well as other documents that may be filed by CuraGen from time to time with the Securities and Exchange Commission. As a result of such risks, uncertainties and factors, CuraGen's actual results may differ materially from any future results, performance or achievements discussed in or implied by the forward-looking statements contained herein. CuraGen is providing the information in this press release as of this date and assumes no obligations to update the information included in this press release or revise any forward-looking statements, whether as a result of new information, future events or otherwise.
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