5142 Background: IGF-IR-mediated signaling contributes to prostate cancer carcinogenesis and pathogenesis and may be associated with hormone resistance. IMC-A12 is a fully human IgG1 MAb that specifically targets the IGF-IR and inhibits ligand binding and signaling. In xenografts, IMC-A12 inhibits growth of both androgen-dependent and -independent prostate cancer. This phase 2, multicenter study was designed to assess the safety and antitumor activity of IMC-A12 in asymptomatic pts with metastatic CRPC who were chemotherapy-naive. Methods: Pts received IMC-A12 10 mg/kg IV every 2 wks; until evidence of progressive disease (PD), intolerable toxicity, or other withdrawal criteria were met. Radiologic evaluation was performed every 8 wks. PD by bone scan required at least 2 new lesions with confirmation at subsequent imaging per PCWG2. Results: 19 of 31 pts treated have discontinued IMC-A12, 12 due to PD. 9 of 31 pts experienced disease stabilization for ≥6 mos (range: 7.4–12.5 mos), 5 pts (3 with PSA reduction) continue on IMC-A12. The most common AEs possibly or probably related to IMC-A12, were fatigue (25.8%) and hyperglycemia (19.4%). In 4 pts cases of Grade 3 hyperglycemia was treatment related none requiring discontinuation of IMC-A12; 1 pt required insulin but continued on study. Approximately 70% of pts experienced at least transient elevation of nonfasting glucose to above normal range. Other AEs grade ≥3 at least possibly related to IMC-A12 were one case each of thrombocytopenia (requiring IMC-A12 discontinuation), hyperkalemia, fatigue, pneumonia (resulting in death), and Grade 4 pharmacokinetic and pharmacodynamic analayses are pending leukoencephalopathy (probably related; requiring IMC-A12 discontinuation). Pharmakinetic and pharmacodynamic analyses are pending. Conclusions: IMC-A12 monotherapy appears well tolerated in pts with metastatic asymptomatic CRPC. As in phase I, hyperglycemia was largely asymptomatic and manageable. Disease stabilization for > 6 months in 9 of 31 pts suggests that IMC- A12 may have modest antitumor activity. Additional studies of IMC-A12 in CRPC are planned. [Table: see text]
Pharmacokinetics, Antitumor Activity, and Safety of ODM-201 in Patients with Chemotherapy-naive Metastatic Castration-resistant Prostate Cancer: An Open-label Phase 1 Study
