PRINCETON, N.J., June 5 /PRNewswire-FirstCall/ -- Medarex, Inc. today announced encouraging safety and response data in patients with hormone refractory prostate cancer (HRPC) from a Phase I clinical trial of ipilimumab (also known as MDX-010) in combination with GM-CSF (sargramostim) and from a separate Phase II clinical trial of ipilimumab alone or in combination with chemotherapy. These data were presented over the weekend at the 42nd Annual Meeting of the American Society of Clinical Oncology, June 2-6, 2006, in Atlanta, GA.
Phase I Trial of Ipilimumab and GM-CSF Combination Yields Promising Results (Abstract #2508)
In the first clinical trial to combine ipilimumab and GM-CSF, a cytokine that stimulates the proliferation of white blood cells and augments immune responses, two of three patients with HRPC treated at the highest dose of ipilimumab (3.0 mg/kg) in this Phase I clinical trial experienced confirmed decreases in prostate specific antigen (PSA) serum levels of greater than 50%.
In the Phase I clinical trial, 18 patients with HRPC received treatment with a 28-day cycle of daily doses of 250 mg/m2 of GM-CSF for 14 days in combination with ipilimumab administered on the first day of the 28-day cycle for four doses, ranging from 0.5 mg/kg to 3.0 mg/kg. The preliminary data showed that the treatment combination was generally well-tolerated. The two responding patients each experienced an Immune Breakthrough Event (IBE), one of rash and the other of hypopituitarism. IBEs are recognized adverse events consistent with an immune-based mechanism of action due to CTLA-4 blockade and appear to be associated with an enhanced likelihood of anti-tumor response in trials of ipilimumab with other tumor types.
“We are encouraged by the responses observed in this early Phase I study, suggesting that ipilimumab may be a potentially active therapy in combination with GM-CSF for prostate cancer,” said Donald L. Drakeman, President and CEO of Medarex.
Ipilimumab and Chemotherapy Phase II Trial Shows Encouraging Responses (Abstract #4609)
In a Phase II clinical trial of ipilimumab alone or in combination with docetaxel, three of the 24 patients with HRPC treated with ipilimumab alone experienced decreases in PSA serum levels of over 50%, with one confirmed response of 246 days in duration, one confirmed response of at least 79 days and one unconfirmed response. Three of the 20 patients treated with ipilimumab in combination with docetaxel experienced decreases in PSA serum levels of over 50%, with one confirmed response of 280 days in duration and two unconfirmed responses.
In the Phase II clinical trial, chemotherapy-naive patients with HRPC were treated with 3.0 mg/kg of ipilimumab monthly for up to four doses and were randomized to receive either ipilimumab alone or ipilimumab in combination with a single dose of 75 mg/m2 of docetaxel administered with the first dose of ipilimumab. Ipilimumab treatment was generally well-tolerated. Serious adverse events were reported in 18 patients, with the majority of the severe adverse events deemed by the investigator to be unrelated to ipilimumab treatment. Overall, four of the 44 patients experienced an IBE, with the most common events being diarrhea, colitis and adrenal or pituitary insufficiency. Two of the four patients with IBEs were among those with PSA responses, a result which is supportive of the correlation between IBEs and enhanced probability of anti-tumor response observed in other ipilimumab clinical trials.
“The data reported from our clinical studies in hormone refractory prostate cancer lay the groundwork for further exploration of the potential of ipilimumab to elicit clinical responses at higher doses as monotherapy or in combination with other chemotherapeutic or immunologic interventions to address the unmet needs of patients with hormone refractory prostate cancer,” said Israel Lowy, MD, PhD, Senior Director of Clinical Science at Medarex.
About ipilimumab
Ipilimumab (also known as MDX-010) is a fully human antibody against human CTLA-4, a molecule on T cells that is believed to be responsible for suppressing the immune response. Medarex and Bristol-Myers Squibb are investigating the potential of ipilimumab to enable the immune systems of cancer patients to help suppress tumor growth. Ipilimumab is currently in two registrational studies for metastatic melanoma under two separate Special Protocol Assessment (SPA) agreements with the FDA. One is a recently initiated monotherapy second-line study that is expected to be completed this year, and the other is a second-line study in combination with MDX-1379 (a melanoma peptide vaccine). A front-line dacarbazine combination registrational study is also expected to initiate this year. Ipilimumab is also involved in multiple Phase II clinical trials to investigate the product’s potential activity in other tumor types, as well as in combination studies with chemotherapy, immunotherapy and vaccines. Further information regarding Medarex’s ipilimumab program can be found in Medarex’s public disclosure filings with the U.S. Securities and Exchange Commission (SEC).
About Medarex
Medarex is a biopharmaceutical company focused on the discovery, development and potential commercialization of fully human antibody-based therapeutics to treat life-threatening and debilitating diseases, including cancer, inflammation, autoimmune disorders and infectious diseases. Medarex applies its UltiMAb(R) technology and product development and clinical manufacturing experience to generate, support and potentially commercialize a broad range of fully human antibody product candidates for itself and its partners. Thirty-two of these therapeutic product candidates derived from Medarex technology are in human clinical testing or have had INDs submitted for such trials, with four of the most advanced product candidates currently in Phase III clinical trials. Medarex is committed to building value by developing a diverse pipeline of antibody products to address the world’s unmet healthcare needs. For more information about Medarex, visit its website at www.medarex.com.
Medarex Statement on Cautionary Factors
Except for the historical information presented herein, matters discussed herein may constitute forward-looking statements that are subject to certain risks and uncertainties that could cause actual results to differ materially from any future results, performance or achievements expressed or implied by such statements. Statements that are not historical facts, including statements preceded by, followed by, or that include the words “potential"; “believe"; “anticipate"; “intend"; “plan"; “expect"; “estimate"; “could"; “may"; or similar statements are forward-looking statements. Medarex disclaims, however, any intent or obligation to update these forward-looking statements. Risks and uncertainties include risks associated with product discovery and development, uncertainties related to the outcome of clinical trials, slower than expected rates of patient recruitment, unforeseen safety issues resulting from the administration of antibody products in patients, uncertainties related to product manufacturing as well as risks detailed from time to time in Medarex’s public disclosure filings with the U.S. Securities and Exchange Commission (SEC), including its Annual Report on Form 10-K for the fiscal year ended December 31, 2005 and subsequent Quarterly Reports on Form 10-Q. There can be no assurance that such development efforts will succeed or that other developed products will receive required regulatory clearance or that, even if such regulatory clearance were received, such products would ultimately achieve commercial success. Copies of Medarex’s public disclosure filings are available from its investor relations department.
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