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- Title
A Phase 1b/2a Study of GC1118 with 5-Fluorouracil, Leucovorin and Irinotecan (FOLFIRI) in Patients with Recurrent or Metastatic Colorectal Cancer.
- Authors
Lee, Keun-Wook; Han, Sae-Won; Kim, Tae Won; Ahn, Joong Bae; Baek, Ji Yeon; Cho, Sang Hee; Lee, Howard; Kim, Jin Won; Kim, Ji-Won; Kim, Tae-You; Hong, Yong Sang; Beom, Seung-Hoon; Cha, Yongjun; Choi, Yoonjung; Kim, Seonhui; Bang, Yung-Jue
- Abstract
Purpose GC1118 is a novel antibody targeting epidermal growth factor receptor (EGFR) with enhanced blocking activity against both low- and high-affinity EGFR ligands. A phase 1b/2a study was conducted to determine a recommended phase 2 dose (RP2D) of GC1118 in combination with 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) (phase 1b) and to assess the safety and efficacy of GC1118 plus FOLFIRI as a second-line therapy for recurrent/metastatic colorectal cancer (CRC) (phase 2a). Materials and Methods Phase 1b was designed as a standard 3+3 dose-escalation study with a starting dose of GC1118 (3 mg/kg/wk) in combination with biweekly FOLFIRI (irinotecan 180 mg/m2; leucovorin 400 mg/m2; 5-fluorouracil 400 mg/m2 bolus and 2,400 mg/m2 infusion over 46 hours) in patients with solid tumors refractory to standard treatments. The subsequent phase 2a part was conducted with objective response rate (ORR) as a primary endpoint. Patients with KRAS/NRAS/BRAF wild-type, EGFR-positive, recurrent/metastatic CRC resistant to the first-line treatment were enrolled in the phase 2a study. Results RP2D of GC1118 was determined to be 3 mg/kg/wk in the phase 1b study (n=7). Common adverse drug reactions (ADRs) observed in the phase 2a study (n=24) were acneiform rash (95.8%), dry skin (66.7%), paronychia (58.3%), and stomatitis (50.0%). The most common ADR of = grade 3 was neutropenia (33.3%). ORR was 42.5% (95% confidence interval [CI], 23.5 to 62.0), and median progression-free survival was 6.7 months (95% CI, 4.0 to 8.0). Conclusion GC1118 administered weekly at 3 mg/kg in combination with FOLFIRI appears as an effective and safe treatment option in recurrent/metastatic CRC.
- Subjects
ACNEIFORM eruptions; CANCER chemotherapy; IRINOTECAN; EPIDERMAL growth factor receptors; COLORECTAL cancer; METASTASIS
- Publication
Cancer Research & Treatment, 2024, Vol 56, Issue 2, p590
- ISSN
1598-2998
- Publication type
Article
- DOI
10.4143/crt.2023.1117