Phase Ii Study Of Cixutumumab (Imc-A12, Nsc742460; C) In Hepatocellular Carcinoma (Hcc)

4043 Background: C is an anti-IGF-1R monoclonal antibody. IGF-IR is implicated in hepatic carcinogenesis. A phase I study of C yielded a partial response in HCC. Methods: Patients (pts) with advanced HCC, Child-Pugh A-B8, and KPS ≥ 60%, received 6 mg/kg of C weekly. The trial had a planned accrual of 50 pts in a two-stage design. Primary endpoints were PFS at 4 months (futility 42%) and response rate (RR), by RECIST (futility 5%). IGF-1R staining was evaluated by immunohistochemistry (IHC), and serum free IGF-I, total IGF-II and IGFBP-1 and -3 were measured by ELISA (Beckman Coulter/DSL) at baseline, and studied for correlation with PFS, OS, and stable disease (SD). Child-Pugh, CLIP, and GETCH scores were similarly measured and studied. Results: The study accrued to the first stage only because of futility. N= 24 with no prior systemic therapy including no sorafenib: median age 67.5 years (range 49-83), KPS 80%(70-90%), 20 males (83%), 9 stage III (37%)/15 stage IV (63%), 11 HBV (46%) /10 HCV (42%), 10 (42%) were diabetic and 5 (21%) became diabetic while on study. The median number of doses was 7 (range 1-140 doses). Grade 3 and 4 toxicities noted in more than 10%: hyperglycemia (46%) which required dose reduction in 3 (12%) pts; elevated liver functions tests: ALT (12%), AST (25%), alkaline phosphatase (12%), and bilirubin (12%); hyponatremia (25%), and lymphopenia (12%). Therapy was discontinued in 2 pts, due to ALT/AST elevation, and hyperglycemia. One pt died after 4 doses due to clinical progression of disease (POD). PFS at 4 months was 30% (95% CI 13-48). There were no objective responses. Of 22 evaluable pts, 7 (29%) had SD for at least 4 months, and 9 (41%) had POD. Median OS was 8 months (95%CI 5.8-14). Within the limitation of the sample size, there was noted a positive correlation between elevation of IGFBP-1 and PFS (1.2 [95%CI 1-1.4]; p 0.009) and OS (1.2 [95%CI 1.1-1.4]; p 0.003). Worse CLIP (3.8 [95%CI 1.3-11.6]; p 0.02) and GETCH (4.6 [95%CI 1.3-16]; p 0.02) scores correlated with worse OS. Conclusions: C is inactive as monotherapy in HCC. Grade 3-4 hyperglycemia occurred in 46% of pts. Within the limitation of the sample size, an elevation of IGFBP-1 did correlate with PFS. Similar to prior reports, worse CLIP and GETCH scores correlated with worse OS.