366 Background: Pmab is a fully human anti-epidermal growth factor receptor monoclonal antibody (mAb) approved as monotherapy for pts with mCRC. AMG 102 and AMG 479 are investigational, fully human mAbs against hepatocyte growth factor (HGF) and insulin-like growth factor receptor 1 (IGF1R), respectively. This 3-part study evaluated the safety and efficacy of AMG 102 or AMG 479 in combination with pmab. Methods: Part 1 was a phase 1b, open-label, dose-finding study to determine a tolerable dose of AMG 102 in combination with pmab. Part 2 was a phase II, randomized, blinded, placebo-controlled trial that explored pmab + the dose of AMG 102 selected in Part 1 vs pmab + AMG 479 vs pmab + placebo. Part 3 is a 2-arm randomized extension study for pts who developed disease progression (PD) or intolerability to pmab + placebo in part 2. Eligible pts were ≥ 18 years old with WT KRAS mCRC and ECOG PS 0/1. In part 1, all pts received 6 mg/kg pmab + 10 mg/kg AMG 102 Q2W IV until PD or intolerability. The primary endpoint of part 1 was the incidence of dose-limiting toxicities (DLTs). The primary endpoint for part 2 is objective response rate (ORR). Results: In part 1, no DLTs were reported for the first 6 DLT-evaluable pts. A total of 11 pts were enrolled in part 1 prior to the decision to use the 10 mg/kg Q2W AMG 102 dose in part 2; 5 pts were men; mean (range) age was 56 (37-75) yrs; ECOG 0/1 was 55%/45%. Grade 3 treatment-related adverse events (AEs) were acneiform dermatitis or rash (55%), paronychia (18%), infection (9%), capillary leak syndrome (9%), erythema (9%), nail disorder (9%), and pruritus (9%). There were no grade 4 or 5 treatment-related AEs. Serious AEs included acneiform dermatitis (n = 1), intestinal obstruction (n = 1), cerebrovascular accident (n = 1), capillary leak syndrome (n = 1), and anemia/general health deterioration (n = 1). One pt died on study from PD. In part 2, 142 pts received at least one dose of study drug; enrollment is complete, and data analyses are ongoing. Conclusions: In part 1, 6 mg/kg pmab + 10 mg/kg AMG 102 Q2W was well tolerated. Primary efficacy results from part 2, including ORR and progression-free survival, will be presented. [Table: see text]