دورية أكاديمية
A Phase 1b/2a Study of GC1118 with 5-Fluorouracil, Leucovorin and Irinotecan (FOLFIRI) in Patients with Recurrent or Metastatic Colorectal Cancer.
| العنوان: | A Phase 1b/2a Study of GC1118 with 5-Fluorouracil, Leucovorin and Irinotecan (FOLFIRI) in Patients with Recurrent or Metastatic Colorectal Cancer. |
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| المؤلفون: | Lee KW; Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea., Han SW; Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.; Seoul National University Cancer Research Institute, Seoul, Korea., Kim TW; Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea., Ahn JB; Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea., Baek JY; Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea., Cho SH; Division of Hemato-Oncology, Department of Internal Medicine, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Hwasun, Korea., Lee H; Department of Clinical Pharmacology and Therapeutics, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.; Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Korea., Kim JW; Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea., Kim JW; Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea., Kim TY; Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.; Seoul National University Cancer Research Institute, Seoul, Korea., Hong YS; Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea., Beom SH; Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea., Cha Y; Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea., Choi Y; GC Biopharma Corp., Yongin, Korea., Kim S; GC Biopharma Corp., Yongin, Korea., Bang YJ; Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea. |
| المصدر: | Cancer research and treatment [Cancer Res Treat] 2024 Apr; Vol. 56 (2), pp. 590-601. Date of Electronic Publication: 2023 Dec 07. |
| نوع المنشور: | Clinical Trial, Phase I; Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: The Association Country of Publication: Korea (South) NLM ID: 101155137 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2005-9256 (Electronic) Linking ISSN: 15982998 NLM ISO Abbreviation: Cancer Res Treat Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Seoul, Korea : The Association, |
| مواضيع طبية MeSH: | Antibodies, Monoclonal, Humanized* , Colonic Neoplasms*/drug therapy , Colorectal Neoplasms*/drug therapy , Colorectal Neoplasms*/genetics , Rectal Neoplasms*/drug therapy, Humans ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Camptothecin/adverse effects ; Camptothecin/therapeutic use ; ErbB Receptors ; Fluorouracil/adverse effects ; Fluorouracil/therapeutic use ; Irinotecan/adverse effects ; Irinotecan/therapeutic use ; Leucovorin/adverse effects ; Leucovorin/therapeutic use ; Neoplasm Recurrence, Local/drug therapy ; Neoplasm Recurrence, Local/etiology |
| مستخلص: | 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/week) 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, 4.0-8.0). Conclusion: GC1118 administered weekly at 3 mg/kg in combination with FOLFIRI appears as an effective and safe treatment option in recurrent/metastatic CRC. |
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| فهرسة مساهمة: | Keywords: Colorectal neoplasms; ErbB receptors; FOLFIRI; GC1118; Irinotecan; Monoclonal antibody |
| المشرفين على المادة: | 0 (Antibodies, Monoclonal, Humanized) XT3Z54Z28A (Camptothecin) EC 2.7.10.1 (ErbB Receptors) U3P01618RT (Fluorouracil) 0 (GC1118) 7673326042 (Irinotecan) Q573I9DVLP (Leucovorin) |
| تواريخ الأحداث: | Date Created: 20231208 Date Completed: 20240415 Latest Revision: 20240607 |
| رمز التحديث: | 20240608 |
| مُعرف محوري في PubMed: | PMC11016642 |
| DOI: | 10.4143/crt.2023.1117 |
| PMID: | 38062706 |
| قاعدة البيانات: | MEDLINE |
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