Efficacy and safety of IBI351 (fulzerasib) monotherapy in KRASG12C inhibitor-naïve Chinese patients with KRAS G12C-mutated metastatic colorectal cancer: a pooled analysis from phase I part of two studies
Abstract IBI351 (also known as fulzerasib or GFH925), an irreversible covalent inhibitor of KRASG12C, has demonstrated promising anti-tumour activity in patients with solid tumours. In this study, data were pooled from the phase I part of two clinical studies (NCT05005234 and NCT05497336), aiming to...
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Nature Publishing Group
2025-07-01
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| Series: | Signal Transduction and Targeted Therapy |
| Online Access: | https://doi.org/10.1038/s41392-025-02315-7 |
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| author | Ying Yuan Yanhong Deng Yongdong Jin Zengqing Guo Yueyin Pan Cunji Wang Zhiwu Wang Yi Hu Dong Hua Xiangjiao Meng Zhiye Zhang Mingfang Zhao Xiaorong Dong Dingzhi Huang Xiaoyan Li Lian Liu Meili Sun Huijuan Wang Xiuwen Wang Nong Yang Mingjun Zhang Sheng Hu Dongde Wu Jingjing Huang Sujie Zhang Mengna Huang Kefeng Ding |
| author_facet | Ying Yuan Yanhong Deng Yongdong Jin Zengqing Guo Yueyin Pan Cunji Wang Zhiwu Wang Yi Hu Dong Hua Xiangjiao Meng Zhiye Zhang Mingfang Zhao Xiaorong Dong Dingzhi Huang Xiaoyan Li Lian Liu Meili Sun Huijuan Wang Xiuwen Wang Nong Yang Mingjun Zhang Sheng Hu Dongde Wu Jingjing Huang Sujie Zhang Mengna Huang Kefeng Ding |
| author_sort | Ying Yuan |
| collection | DOAJ |
| description | Abstract IBI351 (also known as fulzerasib or GFH925), an irreversible covalent inhibitor of KRASG12C, has demonstrated promising anti-tumour activity in patients with solid tumours. In this study, data were pooled from the phase I part of two clinical studies (NCT05005234 and NCT05497336), aiming to evaluate the efficacy and safety of IBI351 monotherapy in KRASG12C inhibitor-naïve Chinese patients with KRAS G12C-mutated metastatic colorectal cancer (CRC). The objective response rate (ORR) was the primary endpoint. Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). As of December 13, 2023, 56 patients treated with IBI351 monotherapy were included. The median duration of treatment was 7.7 months (range: 0.3–16.7). The confirmed ORR was 44.6% (95% CI: 31.3–58.5), with a DCR of 87.5% (95% CI: 75.9–94.8). With a median follow-up of 13.8 months, the median PFS was 8.1 months (95% CI: 5.5–13.8). The median OS was 17.0 months (95% CI: 12.6–not reached). Treatment-related adverse events (TRAEs) occurred in 53 patients (94.6%), with grade 3 TRAEs in 14 patients (25.0%). No grade 4 or 5 TRAEs were observed. The most common grade 3 TRAEs were anaemia (n = 4, 7.1%) and gamma-glutamyltransferase increased (n = 3, 5.4%). TRAEs led to dose interruption in 12 patients (21.4%) and dose reduction in six patients (10.7%). No TRAEs resulted in treatment discontinuation. IBI351 demonstrated encouraging clinical efficacy and a manageable safety profile in KRASG12C inhibitor-naïve Chinese patients with KRAS G12C-mutated metastatic CRC. |
| format | Article |
| id | doaj-art-ac354e2ced754f8395f2bf98ef944672 |
| institution | Kabale University |
| issn | 2059-3635 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Publishing Group |
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| series | Signal Transduction and Targeted Therapy |
| spelling | doaj-art-ac354e2ced754f8395f2bf98ef9446722025-08-20T03:43:37ZengNature Publishing GroupSignal Transduction and Targeted Therapy2059-36352025-07-011011910.1038/s41392-025-02315-7Efficacy and safety of IBI351 (fulzerasib) monotherapy in KRASG12C inhibitor-naïve Chinese patients with KRAS G12C-mutated metastatic colorectal cancer: a pooled analysis from phase I part of two studiesYing Yuan0Yanhong Deng1Yongdong Jin2Zengqing Guo3Yueyin Pan4Cunji Wang5Zhiwu Wang6Yi Hu7Dong Hua8Xiangjiao Meng9Zhiye Zhang10Mingfang Zhao11Xiaorong Dong12Dingzhi Huang13Xiaoyan Li14Lian Liu15Meili Sun16Huijuan Wang17Xiuwen Wang18Nong Yang19Mingjun Zhang20Sheng Hu21Dongde Wu22Jingjing Huang23Sujie Zhang24Mengna Huang25Kefeng Ding26Department of Medical Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, Second Affiliated Hospital of Zhejiang University School of MedicineDepartment of Medical Oncology, The Sixth Affiliated Hospital of Sun Yat-sen UniversityDepartment of Medical Oncology, Sichuan Cancer HospitalDepartment of Special Demand Ward/Department of Clinical Nutrition, Fujian Cancer HospitalDepartment of Tumor Chemotherapy, Anhui Provincial HospitalDepartment of Oncology, Hunan Traditional Chinese Medical College No.1 Affiliated HospitalThe Second Department of Radiochemotherapy, Tangshan People’s HospitalDepartment of Medical Oncology, Chinese PLA General HospitalDepartment of Oncology, Wuxi People’s HospitalThoracic Radiation Oncology Ward IV, Shandong Provincial Cancer HospitalDepartment of Medical Oncology, The First Affiliated Hospital of Henan University of Science and TechnologyDepartment of Medical Oncology, The First Hospital of China Medical UniversityDepartment of Thoracic Oncology, Union Hospital Affiliated to Tongji Medical College of Huazhong University of Science and TechnologyDepartment of Pulmonary Oncology, Tianjin Medical University Cancer Institute and HospitalDepartment of Medical Oncology, Beijing Tiantan Hospital of Capital Medical UniversityDepartment of Medical Oncology, Qilu Hospital of Shandong UniversityDepartment of Medical Oncology, Central Hospital Affiliated to Shandong First Medical UniversityDepartment of Medical Oncology, The Affiliated Cancer Hospital of Zhengzhou University/Henan Cancer HospitalDepartment of Medical Oncology, Qilu Hospital of Shandong University (Qingdao)Department of Pulmonary Gastroenterology, The Second People’s Hospital of Hunan ProvinceDepartment of Oncology, The Second Affiliated Hospital of Anhui Medical UniversityHepatopancreatobiliary Surgery Department, Hubei Cancer HospitalHepatopancreatobiliary Surgery Department, Hubei Cancer HospitalInnovent Biologics Co., Ltd.Innovent Biologics Co., Ltd.Innovent Biologics Co., Ltd.Department of Colorectal Surgery and Oncology, Center for Medical Research and Innovation in Digestive System Tumors, Ministry of Education, Second Affiliated Hospital of Zhejiang University School of MedicineAbstract IBI351 (also known as fulzerasib or GFH925), an irreversible covalent inhibitor of KRASG12C, has demonstrated promising anti-tumour activity in patients with solid tumours. In this study, data were pooled from the phase I part of two clinical studies (NCT05005234 and NCT05497336), aiming to evaluate the efficacy and safety of IBI351 monotherapy in KRASG12C inhibitor-naïve Chinese patients with KRAS G12C-mutated metastatic colorectal cancer (CRC). The objective response rate (ORR) was the primary endpoint. Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). As of December 13, 2023, 56 patients treated with IBI351 monotherapy were included. The median duration of treatment was 7.7 months (range: 0.3–16.7). The confirmed ORR was 44.6% (95% CI: 31.3–58.5), with a DCR of 87.5% (95% CI: 75.9–94.8). With a median follow-up of 13.8 months, the median PFS was 8.1 months (95% CI: 5.5–13.8). The median OS was 17.0 months (95% CI: 12.6–not reached). Treatment-related adverse events (TRAEs) occurred in 53 patients (94.6%), with grade 3 TRAEs in 14 patients (25.0%). No grade 4 or 5 TRAEs were observed. The most common grade 3 TRAEs were anaemia (n = 4, 7.1%) and gamma-glutamyltransferase increased (n = 3, 5.4%). TRAEs led to dose interruption in 12 patients (21.4%) and dose reduction in six patients (10.7%). No TRAEs resulted in treatment discontinuation. IBI351 demonstrated encouraging clinical efficacy and a manageable safety profile in KRASG12C inhibitor-naïve Chinese patients with KRAS G12C-mutated metastatic CRC.https://doi.org/10.1038/s41392-025-02315-7 |
| spellingShingle | Ying Yuan Yanhong Deng Yongdong Jin Zengqing Guo Yueyin Pan Cunji Wang Zhiwu Wang Yi Hu Dong Hua Xiangjiao Meng Zhiye Zhang Mingfang Zhao Xiaorong Dong Dingzhi Huang Xiaoyan Li Lian Liu Meili Sun Huijuan Wang Xiuwen Wang Nong Yang Mingjun Zhang Sheng Hu Dongde Wu Jingjing Huang Sujie Zhang Mengna Huang Kefeng Ding Efficacy and safety of IBI351 (fulzerasib) monotherapy in KRASG12C inhibitor-naïve Chinese patients with KRAS G12C-mutated metastatic colorectal cancer: a pooled analysis from phase I part of two studies Signal Transduction and Targeted Therapy |
| title | Efficacy and safety of IBI351 (fulzerasib) monotherapy in KRASG12C inhibitor-naïve Chinese patients with KRAS G12C-mutated metastatic colorectal cancer: a pooled analysis from phase I part of two studies |
| title_full | Efficacy and safety of IBI351 (fulzerasib) monotherapy in KRASG12C inhibitor-naïve Chinese patients with KRAS G12C-mutated metastatic colorectal cancer: a pooled analysis from phase I part of two studies |
| title_fullStr | Efficacy and safety of IBI351 (fulzerasib) monotherapy in KRASG12C inhibitor-naïve Chinese patients with KRAS G12C-mutated metastatic colorectal cancer: a pooled analysis from phase I part of two studies |
| title_full_unstemmed | Efficacy and safety of IBI351 (fulzerasib) monotherapy in KRASG12C inhibitor-naïve Chinese patients with KRAS G12C-mutated metastatic colorectal cancer: a pooled analysis from phase I part of two studies |
| title_short | Efficacy and safety of IBI351 (fulzerasib) monotherapy in KRASG12C inhibitor-naïve Chinese patients with KRAS G12C-mutated metastatic colorectal cancer: a pooled analysis from phase I part of two studies |
| title_sort | efficacy and safety of ibi351 fulzerasib monotherapy in krasg12c inhibitor naive chinese patients with kras g12c mutated metastatic colorectal cancer a pooled analysis from phase i part of two studies |
| url | https://doi.org/10.1038/s41392-025-02315-7 |
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