First-In-Human Study Of Mm-141: A Novel Tetravalent Monoclonal Antibody Targeting Igf-1r And Erbb3.

384 Background: MM-141 is a novel tetravalent bispecific monoclonal antibody that binds IGF-1R and ErbB3 and blocks both ligand dependent and independent IGF-1R/ErbB3/PI3K/AKT/mTOR signaling. MM-141 potentiated gemcitabine, nab-paclitaxel, docetaxel, irinotecan, tamoxifen, and everolimus in preclinical models. A multi-arm Phase 1 study is ongoing and the monotherapy dose-escalation portion of the study is completed. Hepatocellular carcinoma (HCC) patients were enrolled to an expansion cohort of Arm A to receive MM-141 as a monotherapy. Another arm of treatment combined MM-141 with gemcitabine and nab-paclitaxel. Methods: This is a Phase 1 dose-escalation study evaluating safety, tolerability, pharmacokinetic (PK), and pharmacodynamic (PD) properties of MM-141 as monotherapy (n=15) and in combination with everolimus (Arm B) or with nab-paclitaxel and gemcitabine (Arm C). Three HCC patients in the Arm A expansion cohort received MM-141 as a monotherapy at a weekly dose of 20 mg/kg. These patients underwent ...