444OPHASE IB TRIAL TRIAL OF RG7116, A GLYCOENGINEERED MONOCLONAL ANTIBODY TARGETING HER3, IN COMBINATION WITH CETUXIMAB OR ERLOTINIB IN PATIENTS WITH ADVANCED/METASTATIC TUMORS OF EPITHELIAL CELL ORIGIN EXPRESSING HER3 PROTEIN

ABSTRACT Aim: To evaluate the safety profile of RG7116 in combination with cetuximab or erlotinib. Methods: Patients (pts) with advanced or metastatic carcinomas with centrally confirmed HER3 protein expression were included. RG7116 plus cetuximab (400 mg/m2 followed by 250 mg/m2 qw IV) and RG7116 plus erlotinib (150 mg/day p.o.) combinations were evaluated in a dose escalation study with “3 + 3” design at a starting dose of 400 mg IV of RG7116 in a q2w regimen. Results: Twenty-seven pts were enrolled in 5 cohorts (400 to 2000 mg) in the cetuximab arm. One dose-limiting toxicity (DLT) of grade 3 dehydration was reported in the 800-mg cohort. Twenty-seven pts were enrolled in 4 cohorts (400 to 2000 mg) in the erlotinib arm. One DLT was reported in the 1600-mg cohort (grade 3 diarrhea and grade 3 hypokalemia) and one DLT was reported in the 2000-mg cohort (grade 3 blood bilirubin increase). No maximum tolerated dose was reached. The most frequently reported adverse events of any grade were diarrhea (78%) and rash (59%) for the cetuximab arm and diarrhea (82%) and decreased appetite (48%) for the erlotinib arm. In the erlotinib arm treatment-related grade 3 diarrhea was observed more frequently at higher doses of RG7116 (400 mg: 0%; 800 mg: 17%; 1600 mg: 43%; 2000 mg: 33%). Overall, infusion-related reactions related to RG7116 occurred in 11% of pts. Two of these were grade 3 (4%). The pharmacokinetic profile of RG7116 in combination with cetuximab and erlotinib was comparable to that in the monotherapy setting (Meulendijks et al. J Clin Oncol 31, 2013 suppl; abstr 2522). HER3 membranous protein down-regulation was observed from 400 mg onwards in on-treatment tumor and skin tissue. In the cetuximab arm, two pts with colorectal carcinoma had a confirmed partial response (PR). In the erlotinib arm, one patient with ovarian carcinoma had a confirmed PR. Metabolic PR on FDG-PET occurred in 42% of pts in the cetuximab arm and in 28% of pts in the erlotinib arm. Conclusions: RG7116 combination with cetuximab or erlotinib was well tolerated, and demonstrated preliminary signs of clinical activity. Disclosure: U.N. Lassen: discloses Research grants from Roche; A. Cervantes Ruiperez: discloses Research grants, advisory boards and lectures for Roche; C. Adessi, A. Keelara, F. Michielin, B. Bossenmaier, G. Meneses-Lorente, I. James, W. Jacob and M. Weisser: Employee of Roche. All other authors have declared no conflicts of interest.