GC1118 is a novel anti-EGFR monoclonal antibody and has unique binding epitopes and different ligand binding inhibitory activity compared to cetuximab and panitumumab. In dose escalation part of a first-in-human phase 1 study, RP2D were determined as 4 mg/kg, in weekly dosing schedule (NCT02352571). DLT was skin toxicity. Here we report efficacy and safety data of GC1118 in patients (pts) with colorectal cancer (CRC) and gastric cancer (GC) tested in dose expansion part.
Cohort 1 (C1) recruited pts with metastatic CRC with no prior EGFR antibody treatment who have failed to 5-FU, oxaliplatin and irinotecan. Cohort 2 (C2) enrolled pts with metastatic CRC with resistance to prior EGFR antibody. Cohort 3 (C3) enrolled pts with EGFR over-expressing (2+,3+) metastatic GC cancer who have failed to standard treatment. GC1118 was administrated on days 1, 8, 15 and 22 every 4 weeks.
A total of 39 pts were enrolled (C1: 14, C2:12, C3:13). Evaluable pts were 12 in each cohort. In C1, SD was observed in 58.33% (7/12) and there was no CR/PR case. In C2, 2 patients (16.67%) obtained PR, 1 SD (8.33%), and 9 PD (75.0%). In C3, PR was 8.33% (1/12), SD 16.67% (2/12), and PD 75.0%. The progression-free survival (PFS) were 14 weeks (95% CI: 7.1-30.1), 6.93 weeks (95% CI: 4.2-14.8), and 6.7 weeks (95% CI: 5.0-11.0), respectively Adverse event (AE) was observed in 97.4% of patients and treatment-related AE (TRAE) occurred in 92.3% of patients. Skin toxicity (all grade) was observed in 89.7% of patients (35/39), stomatitis 20.51%( all grade 1/2), and diarrhea 17.95% (all grade 1/2). Dose reduction due to AE was required in 23.08% of patients (9/39), and dose interruption due to AE was needed in 58.9% of patients (23/39). TRAE higher than grade 3 was observed in 20.5% of patients (8/39). Among them, skin toxicity was most common (12.8%, 5/39 patients) There was no treatment-related death.
GC1118 showed promising anti-tumor activity, especially in CRC with resistance to prior EGFR antibody with 16.7% PR, even in heavily treated population. GC1118 was generally well tolerated, and skin toxicities were by far the most common AEs.
Clinical trial identification
Legal entity responsible for the study
Green Cross Corp., Seoul National University Hospital.
Green Cross Corp.
N.H. Kim, A. Woo, J. Won: Employee: Pharmaceutical company. All other authors have declared no conflicts of interest.