Phase Ib/IIa study of GC1118 in combination with irinotecan or FOLFIRI in patients with metastatic solid tumors.

Abstract

3592 Background: GC1118 is a novel anti-EGFR monoclonal antibody which has a unique binding epitope and superior ligand inhibition potential. It showed promising antitumor activity as a single agent in the phase I study. This study aimed to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of GC1118 in combination with irinotecan or FOLFIRI in metastatic solid tumors and evaluate the efficacy of GC1118 plus FOLFIRI as a second line therapy for RAS and BRAF wild-type metastatic colorectal cancer. Methods: Phase 1b part was designed to evaluate weekly GC1118 (starting from 3 mg/kg) in combination with biweekly irinotecan (180mg/m2) or FOLFIRI (irinotecan 180mg/m2, leucovorin 400mg/m2, 5-FU 400 mg/m2 bolus, and 5-FU 2400mg/m2 over 46hrs) in a 3+3 design. In the phase 2a part, the RP2D of GC1118 is administered in combination with FOLFIRI in a Simon’s two stage design with objective response rate (ORR) as the primary endpoint. Results: 13 pts were enrolled in phase 1b and received 3mg/kg of GC1118 with irinotecan (N = 6) or FOLFIRI (N = 7). DLT occurred in 2 pts (G4 neutropenia, G2 rash) in irinotecan arm and 1pt (G3 neutropenia) in FOLFIRI arm with 3mg/kg of GC1118 and it was determined as MTD and RP2D. Adverse events (AE) of grade ≥ 3 included neutropenia (61.5 %), skin rash (15.4 %) and diarrhea (15.4%). Dose reductions due to GC1118-related AE were required in 6 (46.2%) patients. Among 10 response-evaluable pts in phase 1b, best overall response was PR in 3 and SD in 6, and median PFS was 12 months. In stage 1 of phase 2a (N = 9), 4 PR and 5 SD were observed (ORR 44.4%, 95% CI 13.7 – 78.8). We moved to stage 2, and are currently enrolling additional 20 pts. AE of grade ≥ 3 included neutropenia (66.7%), skin rash (22.2%) and diarrhea (11.1%). Updated data of the phase 2a part will be presented at the meeting. Conclusions: The MTD and RP2D of weekly GC1118 in combination with irinotecan or FOLFIRI was 3mg/kg. Preliminary results of GC1118 and FOLFIRI as a 2nd line treatment in mCRC suggests promising antitumor activity and acceptable safety profile. Clinical trial information: NCT03454620 .