Background: GC1118 is a novel anti-EGFR monoclonal antibody and has unique binding epitopes and affinity. We conduct a first-in-human phase 1 study to investigate the maximum tolerated dose (MTD), recommended phase 2 dose (RP2D), safety, pharmacokinetics, and preliminary efficacy of GC118 in patients with refractory solid tumors (NCT02352571). Methods: GC1118 was intravenously administrated over 2 hours on days 1, 8, 15 and 22 followed by additional 2 week rest in the first cycle, during which dose limiting toxicities (DLTs) were evaluated. If there was no tumor progression, GC1118 was administrated weekly thereafter. Dose escalation was guided by a Bayesian logistic regression model with overdose control. Results: Twenty-four patients, 17 with colorectal cancer (CRC), were treated with GC1118 at five dose levels: 0.3 mg/kg (n = 4), 1.0 mg/kg (n = 4), 3.0 mg/kg (n = 4), 4.0 mg/kg (n = 6) and 5.0 mg/kg (n = 6). In the 5.0 mg/kg cohort, two patients experienced DLTs, which were grade 3 skin toxicities. No DLTs were observed in the other cohorts. The MTD was determined as 5.0 mg/kg. GC1118-related adverse events (AEs; ≥ 10%) included skin toxicities [pruritus (58%), dermatitis acneiform (50%), dry skin (42%), paronychia (29%) and maculo-papular rash (25%)] and stomatitis (29%). Diarrhea developed in 2 patients ( ≤ grade 2). AEs of grade ≥ 3 included skin (n = 2) and hepatic toxicities (n = 1). Pharmacokinetic study showed typical target-mediated drug disposition profiles via ligand-receptor coupling. Considering toxicity and pharmacokinetic data, 4.0 mg/kg was determined as the RP2D. Partial response (PR) was shown in 3 patients (all with CRC) and stable disease in 12. Median progression-free survival was 13.3 weeks (95% confidence interval: 5.1-21.1). Expansion cohorts were opened, and updated results will be presented. Conclusions: We determined the MTD as 5 mg/kg and the RP2D as 4 mg/kg. DLTs were grade 3 skin toxicities. GC1118 was generally well tolerated. Skin toxicities were the most common AEs and diarrhea was uncommon. GC1118 showed promising preliminary anti-tumor activity, especially in wild-type KRAS CRC with 3 PRs (18%) among 17 patients. Clinical trial information: NCT02352571