Abituzumab (Di17e6, Emd 525797) Treatment For Chemotherapy-Naive Patients With Asymptomatic Or Mildly Symptomatic Metastatic Castration-Resistant Prostate Cancer (Mcrpc): Primary Outcomes Of The Placebo-Controlled Phase 2 Study Perseus (Nct01360840)

ABSTRACT Aim: Abituzumab, a humanized monoclonal IgG2 antibody (Ab) targeting av integrins, suppressed tumor growth in preclinical models and was well tolerated in a phase 1 study in mCRPC patients (pts). This exploratory double-blind trial investigated abituzumab 750 or 1500 mg vs placebo added to standard of care in mCRPC pts. Methods: Eligible pts had radiologic disease progression (rPD) of bone lesions Results: Median PFS (ITT) was 3.3, 3.4 (HR = 0.89 [95% CI: 0.57, 1.39]), and 4.3 months (HR = 0.81 [95% CI: 0.52, 1.26]) with placebo, abituzumab 750, and 1500 mg, respectively. PD was reported in 72, 68, and 65% of pts, respectively, incl. bone lesion PD in 42% of the control arm and in 23% of each abituzumab arm. Less than 2 new bone lesions at weeks 12, 18, and 24, respectively, were reported in 7, 3, and 3% of pts receiving placebo; in 12, 12, and 7% of pts treated with abituzumab 750 mg; and in 12, 10, and 5% of pts receiving abituzumab 1500 mg. of 74 OR-evaluable pts with ST lesions at baseline (BL), 1 pt each receiving placebo or abituzumab 1500 mg achieved partial response. Abituzumab's previously reported safety profile was confirmed. Generation of Abs directed against abituzumab was low: binding Abs were detected post-BL in 3/45, 5/44, and 2/49 evaluable pts treated with placebo, abituzumab 750, and 1500 mg, respectively (highest post-BL level). Candidate BMs (eg, decorin) predictive of prolonged PFS (HR = 0.44 [95% CI: 0.24, 0.83]) with abituzumab were identified. Conclusions: Median PFS with abituzumab 1500 mg was modestly longer than with 750 mg or placebo. Compared with placebo, pts receiving abituzumab experienced bone lesion PD less frequently. Further analysis of clinical efficacy is needed. Disclosure: K. Miller: Consultant or advisory role for, and honoraria from Merck KGaA; M. Hussain: Research funding from Merck KGaA, Genentech, Pfizer, and Medivation for clinical trials (contract with University of Michigan); S. Le Moulec: Advisory board for Astellas, Bayer, and Sanofi; I. Rybicka, R. Bruns and J. Straub: Employee of Merck KGaA.