GC-1118A / GC Biopharma - LARVOL DELTA

Anti-EGFR in combination with paclitaxel as second-line therapy for gastric cancer with EGFR overexpression (AACR 2024) - P2 | "(This study was supported by a grant from the National R&D Program for Cancer Control, Ministry of Health & Welfare, Republic of Korea (HA22C0056.)) Background: We and other investigators reported that EGFR gene is amplified in 2-4% of gastric cancer with protein overexpression (Gastroenterology 2017 Aug; 153(2):536-549; Cancer Cell 2019 Jan 14; 35:1:111:E10), but EGFR-targeted therapy has not entered into clinic.Patients and As a subprotocol of the investigator-initated of umbrella trial, patients with metastatic gastric cancer received weekly anti-EGFR monoclonal antibody (GC-1118 (GC Biopharma), 2.5mg/kg) in combination with paclitaxel 80mg/m2 (D1, D8, D15) every 4 weeks as a second-line therapy, if the gastric cancer tissue sample revealed EGFR protein overexpression (NCT04077255)... EGFR inhibition, in combination with paclitaxel, demonstrated modest activity for gastric cancer refractory to first-line 5-FU/platinum-based chemotherapy."

Clinical • Combination therapy • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

A Phase 1b/2a Study of GC1118 with 5-Fluorouracil, Leucovorin and Irinotecan (FOLFIRI) in Patients with Recurrent or Metastatic Colorectal Cancer. (PubMed, Cancer Res Treat) - "ORR was 42.5% (95% confidence interval [CI], 23.5-62.0), and median progression-free survival was 6.7 months (95% CI, 4.0-8.0). GC1118 administered weekly at 3 mg/kg in combination with FOLFIRI appears as an effective and safe treatment option in recurrent/metastatic CRC."

Journal • Metastases • P1/2 data • Colorectal Cancer • Dental Disorders • Gastrointestinal Cancer • Hematological Disorders • Neutropenia • Oncology • Solid Tumor • Stomatitis • BRAF • EGFR • KRAS

A multicenter, phase II trial of GC1118, a novel anti-EGFR antibody, for recurrent glioblastoma patients with EGFR amplification. (PubMed, Cancer Med) - "This study did not meet the primary endpoint (PFS6); however, we found that immune signatures were significantly upregulated in the tumors with regression upon GC1118 therapy, which signifies the potential of immune-mediated antitumor efficacy of GC1118."

Journal • P2 data • Brain Cancer • CNS Tumor • Dermatology • Glioblastoma • Oncology • Solid Tumor

GC1118 in Recurrent Glioblastoma Patients With High EGFR Amplification (clinicaltrials.gov) - P2 | N=13 | Completed | Sponsor: Samsung Medical Center | Unknown status ➔ Completed | N=23 ➔ 13

Enrollment change • Trial completion • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • EGFR

EGFR-targeted Therapy for Gastric Cancer (clinicaltrials.gov) - P2 | N=19 | Recruiting | Sponsor: National Cancer Center, Korea | N=38 ➔ 19 | Trial primary completion date: Dec 2022 ➔ Dec 2023

Combination therapy • Enrollment change • Trial primary completion date • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • EGFR

A Study to Assess Safety, Efficacy, Immunogenicity, PK of GC1118 With Combination Chemotherapy (clinicaltrials.gov) - P1b/2a | N=53 | Completed | Sponsor: Green Cross Corporation | Active, not recruiting ➔ Completed | Trial completion date: Jun 2021 ➔ Jan 2022

Combination therapy • Trial completion • Trial completion date • Colorectal Cancer • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • BRAF • EGFR • HER-2 • KRAS • NRAS

Therapeutic efficacy of GC1118, a novel anti-EGFR antibody, against glioblastoma with high EGFR amplification in patient-derived xenografts (SNO 2021) - "Compared to cetuximab, GC1118 exerted comparable growth inhibitory effects on the GBM tumors in the PDX models. Our study supports the importance of patient stratification based on EGFR copy number variation in clinical trials for GBM. The superiority of GC1118 over other EGFR mAbs in GBM tumors should be assessed in future studies."

Clinical • Brain Cancer • Glioblastoma • Immunology • Oncology • Solid Tumor

A first-in-human phase 1 study of GC1118, a novel monoclonal antibody inhibiting epidermal growth factor receptor (EGFR), in patients with colorectal cancer and gastric/GEJ cancer (ESMO 2018) - P1; "Background: GC1118 is a novel anti-EGFR monoclonal antibody and has unique binding epitopes and different ligand binding inhibitory activity compared to cetuximab and panitumumab... Cohort 1 (C1) recruited pts with metastatic CRC with no prior EGFR antibody treatment who have failed to 5-FU, oxaliplatin and irinotecan... 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 • P1 data • Colorectal Cancer • Gastric Cancer

[VIRTUAL] Phase Ib/IIa study of GC1118 in combination with irinotecan or FOLFIRI in patients with metastatic solid tumors. (ASCO 2020) - P1b/2a | " 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. 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. Research Funding: Green Cross Corporation"

Clinical • Combination therapy • P1/2 data • Colorectal Cancer • Dermatology • Gastrointestinal Cancer • Hematological Disorders • Neutropenia • Oncology • Solid Tumor • BRAF

EGFR-targeted Therapy for Gastric Cancer (clinicaltrials.gov) - P2; N=38; Recruiting; Sponsor: National Cancer Center, Korea; Not yet recruiting ➔ Recruiting; N=85 ➔ 38

Clinical • Combination therapy • Enrollment change • Enrollment open • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • EGFR • MRI

A Study to Assess Safety, Efficacy, Immunogenicity, PK of GC1118 With Combination Chemotherapy (clinicaltrials.gov) - P1b/2a; N=53; Active, not recruiting; Sponsor: Green Cross Corporation; Recruiting ➔ Active, not recruiting; Trial completion date: Mar 2020 ➔ Jun 2021; Trial primary completion date: Mar 2020 ➔ Jun 2021

Clinical • Combination therapy • Enrollment closed • Trial completion date • Trial primary completion date • Colorectal Cancer • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • BRAF • EGFR • HER-2 • KRAS • NRAS

A Target-Mediated Drug Disposition Population Pharmacokinetic Model of GC1118, a Novel Anti-EGFR Antibody, in Patients with Solid Tumors. (PubMed, Clin Transl Sci) - "Monte-Carlo simulation experiments of the PK profiles and EGFR receptor occupancies (RO) by GC1118 based on the final model showed that Q1W at 4 or 5 mg/kg will produce a better anti-tumor effect than Q2W at 8 mg/kg. Because GC1118 was safer at 4 mg/kg than 5 mg/kg in the phase I study, we suggest to test the 4 mg/kg Q1W regimen in further clinical trials with GC1118."

Clinical • Journal • PK/PD data • Oncology • Solid Tumor

GC1118, a novel anti-EGFR andtibody, shows more potent antitumor activity regardless of KRAS mutation or high-affinity lignad stimulation compared with cetuximab in gastric cancer (AACR 2018) - "...GC1118 is a novel anti-EGFR antibody with distinct binding epitope compared to cetuximab or panitumumab, and has superior inhibitory activity against high-affinity EGFR ligands (Mol Cancer Ther 2016)...The synergistic efficacy was observed when cells were treated with GC1118 in combination with cytotoxic chemotherapeutic agents (cisplatin or 5FU) in colony formation assay and migration assay compared to each treatment alone, even under the EGFR-ligand stimulation condition... GC1118 showed more potent antitumor effects in GC compared with cetuximab. In combination with cytotoxic chemotherapy, GC1118 also has more potent activity compared with cetuximab regardless of KRAS mutation status or high-affinity ligand stimulation condition. This study supports further clinical development of GC1118 in gastric cancer."

Gastric Cancer

Therapeutic Efficacy of GC1118, a Novel Anti-EGFR Antibody, against Glioblastoma with High EGFR Amplification in Patient-Derived Xenografts. (PubMed, Cancers (Basel)) - "Compared to cetuximab, GC1118 exerted comparable growth inhibitory effects on the GBM tumors in the PDX models. Our study supports the importance of patient stratification based on EGFR copy number variation in clinical trials for GBM. The superiority of GC1118 over other EGFR mAbs in GBM tumors should be assessed in future studies."

Clinical • Journal • Glioblastoma • Oncology • Solid Tumor

A First-in-Human Phase I Study of GC1118, a Novel Anti-Epidermal Growth Factor Receptor Antibody, in Patients with Advanced Solid Tumors. (PubMed, Oncologist) - "GC1118 showed promising antitumor activity and was well tolerated. Infrequent diarrhea compared with other anti-EGFR antibodies might be advantageous for further development."

Clinical • Journal • P1 data • Colorectal Cancer • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

GC1118 in Recurrent Glioblastoma Patients With High EGFR Amplification (clinicaltrials.gov) - P2; N=23; Recruiting; Sponsor: Samsung Medical Center; Trial completion date: Jul 2020 ➔ Jul 2021; Trial primary completion date: Jan 2020 ➔ Dec 2020

Clinical • Trial completion date • Trial primary completion date • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • EGFR

A Study to Assess Safety, Efficacy, Immunogenicity, PK of GC1118 With Combination Chemotherapy (clinicaltrials.gov) - P1b/2a; N=53; Recruiting; Sponsor: Green Cross Corporation; Not yet recruiting ➔ Recruiting

Enrollment open • Biosimilar • Colorectal Cancer • Gastric Cancer

[ASCO 2020] GC confirms safety, efficacy of anti-EGFR monoclonal antibody (Korea Biomedical Review) - P1/2, N=53; NCT03454620; Sponsor: Green Cross Corporation; "GC has come up with optimal interim results for its phase 1b/2a clinical trials for GC1118, an anti-epidermal growth factor receptor (EGFR) monoclonal antibody for treating colorectal cancer...Among 10 response-evaluable patients in the Phase 1b clinical trial, there were three partial response (PR) and six stable-disease (SD) patients, while the median progression-free survival was 12 months. Based on the results, the company is conducting phase 2a clinical trials in 29 patients."

P1 data • Trial status • Colorectal Cancer • Oncology

Promising Therapeutic Efficacy of GC1118, an Anti-EGFR Antibody, against KRAS Mutation-Driven Colorectal Cancer Patient-Derived Xenografts. (PubMed, Int J Mol Sci) - "Epidermal growth factor receptor (EGFR)-targeted monoclonal antibodies, including cetuximab and panitumumab, are used to treat metastatic colorectal cancer (mCRC)...In support of these findings, a preliminary improved anti-cancer response was observed in a CRC PDX harboring mutated KRAS with intrinsically high AKT activity using GC1118 combined with the dual PI3K/mammalian target of rapamycin (mTOR)/AKT inhibitor BEZ-235, without observed toxicity. Taken together, the superior antitumor efficacy of GC1118 alone or in combination with PI3K/mTOR/AKT inhibitors shows great therapeutic potential for the treatment of KRAS-mutant mCRC with elevated ratios of high- to low-affinity EGFR ligands and PI3K-AKT pathway activation."

Clinical • Journal • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

GC1118, a novel anti-EGFR antibody, has potent KRAS mutation-independent antitumor activity compared with cetuximab in gastric cancer. (PubMed, Gastric Cancer) - "Taken together, GC1118 alone or in combination with cytotoxic chemotherapeutic agents exerted more potent anti-tumor effects than cetuximab in GC cells, regardless of KRAS status. These findings support the further clinical development of GC1118 for the treatment of GC."

Journal

Preclinical in vivo screening to predict responder patients depend on EGFR status (ESMO 2019) - " To figure out clinical criteria for cancer patients, we tested a novel EGFR targeted antibody (GC1118) in glioblastoma patient-derived xenograft (PDX) models and patient-derived cell (PDC) with its genomic data... Overall, this study results suggest that EGFR amplification status is still one of the important criteria to find responder group in glioblastoma patients. Legal entity responsible for the study: The authors. Funding: The Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea."

EGFR/FGFR-targeted Therapy for Gastric Cancer (clinicaltrials.gov) - P2; N=85; Not yet recruiting; Sponsor: National Cancer Center, Korea

Clinical • Combination therapy • New P2 trial