965TiP - A Phase II Study (PERSEUS) of Two Doses of EMD 525797 (DI17E6) in Patients (PTS) with Asymptomatic or Mildly Symptomatic Metastatic Castrate-Resistant Prostate Cancer (MCRPC)

Abstract

ABSTRACT Purpose Expression and function of αv-integrins are deregulated in prostate cancer, and αv-integrins are thought to play an important role in prostate cancer metastasis. EMD 525797 (DI17E6) is a humanized monoclonal IgG2 antibody specifically directed against αv integrin receptors (αvs1, αvs3, αvs5, αvs6, and αvs8). It has been shown to target tumor cells, the tumor's environment (e.g. osteoclasts and osteoblasts), as well as angiogenic blood vessels. Previous studies with EMD 525797 have shown a favorable tolerability profile in healthy volunteers and in mCRPC pts. A phase II trial is investigating the anticancer activity of 2 dose levels of EMD 525797 in asymptomatic or mildly symptomatic mCRPC pts. Methods Adult pts with CRPC who show radiologic progression of bone lesions with/without soft tissue lesions within 28 days prior to randomization are eligible for inclusion. Exclusion criteria are: acute pathologic fracture, spinal cord compression, or hypercalcemia at screening; prior chemotherapy, biologic, or experimental therapy for mCRPC; or radiotherapy to bone lesions and/or orthopedic surgery for pathologic fractures. A total of 216 pts receiving standard of care (luteinizing hormone-releasing hormone [LHRH] antagonists) and bisphosphonate therapy will be randomized 1:1:1 to receive in a blinded manner placebo, 1500 mg or 750 mg EMD 525797 (all 1-h intravenous [IV] infusions) on day 1 of every 3-week cycle until radiographic disease progression (PD). At progression, therapy will be unblinded and pts in the placebo group who show asymptomatic or mildly symptomatic radiographic confirmed PD can receive open-label therapy with 1500 mg EMD 525797. The primary endpoint is composite progression-free survival, defined as the time (months) from randomization date to first documented sign of objective radiographic PD or death from any cause. Secondary endpoints include efficacy (e.g. overall survival and time to progression), safety, the pharmacokinetic profile of EMD 525797, and the exploration of a relationship between the number of circulating tumor cells and clinical outcomes. As of April 2012, 106 pts have entered the trial. Disclosure K. Miller: Membership on an advisory board for Merck KGaA, Darmstadt, Germany, G. Mordenti: Employee of Merck KGaA, Darmstadt, Germany, H. Lannert: Employee of Merck KGaA, Darmstadt, Germany. All other authors have declared no conflicts of interest.