A phase Ia study of a novel anti-HER2 antibody–drug conjugate GQ1001 in patients with previously treated HER2 positive advanced solid tumors
Abstract Background A novel anti-human epidermal growth factor receptor 2 (HER2) antibody–drug conjugate (ADC) GQ1001 was assessed in patients with previously treated HER2 positive advanced solid tumors in a global multi-center phase Ia dose escalation trial. Methods In this phase Ia trial, a modifi...
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2025-01-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | https://doi.org/10.1186/s12967-024-05985-z |
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| author | Chenfei Zhou Bin Wang Christina Teng Hui Yang Sarina A. Piha-Paul Gary Richardson Ashanya Malalasekera Yajun Sun Wei Wang Jieqiong Liu Yan Shi Xianbao Zhan Charlotte Lemech |
| author_facet | Chenfei Zhou Bin Wang Christina Teng Hui Yang Sarina A. Piha-Paul Gary Richardson Ashanya Malalasekera Yajun Sun Wei Wang Jieqiong Liu Yan Shi Xianbao Zhan Charlotte Lemech |
| author_sort | Chenfei Zhou |
| collection | DOAJ |
| description | Abstract Background A novel anti-human epidermal growth factor receptor 2 (HER2) antibody–drug conjugate (ADC) GQ1001 was assessed in patients with previously treated HER2 positive advanced solid tumors in a global multi-center phase Ia dose escalation trial. Methods In this phase Ia trial, a modified 3 + 3 study design was adopted during dose escalation phase. Eligible patients were enrolled, and GQ1001 monotherapy was administered intravenously every 3 weeks. The starting dose was 1.2 mg/kg, followed by 2.4, 3.6, 4.8, 6.0, 7.2 and 8.4 mg/kg. Extra patients were enrolled into 6.0, 7.2, and 8.4 mg/kg cohorts as dose expansion phase. The primary endpoints were safety and to determine the maximum tolerated dose (MTD) based on dose limiting toxicities (DLTs). Pharmacokinetics and anti-tumor efficacy of GQ1001 were assessed. The plasma concentration of free DM1, the payload of GQ1001, was quantitated. Results A total of 32 patients were enrolled, predominantly in breast (9), gastric or gastro-esophageal junction (9) and salivary gland cancer (4). Median number of prior-line of therapies was 3 (0–11) and 37.5% patients received ≥ 2 lines of anti-HER2 therapies. No DLT was observed during dose escalation. MTD was not reached and dose recommended for dose expansion (DRDE) was determined as 8.4 mg/kg. Grade ≥ 3 treatment-related adverse events rate was 28.1% (9/32) and platelet count decreased (4/32, 12.5%) was the most common one. No drug-related death was observed. Objective response rate and disease control rate of 15 evaluable patients in 7.2 mg/kg and 8.4 mg/kg cohorts were 40.0% (6/15) and 60.0% (9/15). Pharmacokinetics analysis showed low exposure and accumulation of free DM1 in circulation. Conclusion GQ1001 is well tolerated and shows promising efficacy in previously treated HER2-positive advanced solid tumors. DRDE was determined as 8.4 mg/kg for following trials. Trial registration NCT, NCT04450732, Registered 23 June 2020, https://clinicaltrials.gov/study/NCT04450732 |
| format | Article |
| id | doaj-art-e756a4c81a2d44cbbb4b97d2d5c8b4e7 |
| institution | Kabale University |
| issn | 1479-5876 |
| language | English |
| publishDate | 2025-01-01 |
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| spelling | doaj-art-e756a4c81a2d44cbbb4b97d2d5c8b4e72025-01-12T12:37:33ZengBMCJournal of Translational Medicine1479-58762025-01-0123111110.1186/s12967-024-05985-zA phase Ia study of a novel anti-HER2 antibody–drug conjugate GQ1001 in patients with previously treated HER2 positive advanced solid tumorsChenfei Zhou0Bin Wang1Christina Teng2Hui Yang3Sarina A. Piha-Paul4Gary Richardson5Ashanya Malalasekera6Yajun Sun7Wei Wang8Jieqiong Liu9Yan Shi10Xianbao Zhan11Charlotte Lemech12Department of Oncology, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Gastroenterology, Changhai Hospital, Naval Medical UniversityScientia Clinical Research and Prince of Wales Clinical School, University of New South WalesDepartment of Oncology, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer CenterDepartment of Medical Oncology, Cabrini HospitalConcord and Bankstown Cancer Centres, Sydney and South Western, Sydney Local Health DistrictGeneQuantum Healthcare (Suzhou) Co.,Ltd.Department of Gastroenterology, Changhai Hospital, Naval Medical UniversityGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen UniversityDepartment of Oncology, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Gastroenterology, Changhai Hospital, Naval Medical UniversityScientia Clinical Research and Prince of Wales Clinical School, University of New South WalesAbstract Background A novel anti-human epidermal growth factor receptor 2 (HER2) antibody–drug conjugate (ADC) GQ1001 was assessed in patients with previously treated HER2 positive advanced solid tumors in a global multi-center phase Ia dose escalation trial. Methods In this phase Ia trial, a modified 3 + 3 study design was adopted during dose escalation phase. Eligible patients were enrolled, and GQ1001 monotherapy was administered intravenously every 3 weeks. The starting dose was 1.2 mg/kg, followed by 2.4, 3.6, 4.8, 6.0, 7.2 and 8.4 mg/kg. Extra patients were enrolled into 6.0, 7.2, and 8.4 mg/kg cohorts as dose expansion phase. The primary endpoints were safety and to determine the maximum tolerated dose (MTD) based on dose limiting toxicities (DLTs). Pharmacokinetics and anti-tumor efficacy of GQ1001 were assessed. The plasma concentration of free DM1, the payload of GQ1001, was quantitated. Results A total of 32 patients were enrolled, predominantly in breast (9), gastric or gastro-esophageal junction (9) and salivary gland cancer (4). Median number of prior-line of therapies was 3 (0–11) and 37.5% patients received ≥ 2 lines of anti-HER2 therapies. No DLT was observed during dose escalation. MTD was not reached and dose recommended for dose expansion (DRDE) was determined as 8.4 mg/kg. Grade ≥ 3 treatment-related adverse events rate was 28.1% (9/32) and platelet count decreased (4/32, 12.5%) was the most common one. No drug-related death was observed. Objective response rate and disease control rate of 15 evaluable patients in 7.2 mg/kg and 8.4 mg/kg cohorts were 40.0% (6/15) and 60.0% (9/15). Pharmacokinetics analysis showed low exposure and accumulation of free DM1 in circulation. Conclusion GQ1001 is well tolerated and shows promising efficacy in previously treated HER2-positive advanced solid tumors. DRDE was determined as 8.4 mg/kg for following trials. Trial registration NCT, NCT04450732, Registered 23 June 2020, https://clinicaltrials.gov/study/NCT04450732https://doi.org/10.1186/s12967-024-05985-zAntibody–drug conjugateGQ1001HER2Solid tumorsDose escalation |
| spellingShingle | Chenfei Zhou Bin Wang Christina Teng Hui Yang Sarina A. Piha-Paul Gary Richardson Ashanya Malalasekera Yajun Sun Wei Wang Jieqiong Liu Yan Shi Xianbao Zhan Charlotte Lemech A phase Ia study of a novel anti-HER2 antibody–drug conjugate GQ1001 in patients with previously treated HER2 positive advanced solid tumors Journal of Translational Medicine Antibody–drug conjugate GQ1001 HER2 Solid tumors Dose escalation |
| title | A phase Ia study of a novel anti-HER2 antibody–drug conjugate GQ1001 in patients with previously treated HER2 positive advanced solid tumors |
| title_full | A phase Ia study of a novel anti-HER2 antibody–drug conjugate GQ1001 in patients with previously treated HER2 positive advanced solid tumors |
| title_fullStr | A phase Ia study of a novel anti-HER2 antibody–drug conjugate GQ1001 in patients with previously treated HER2 positive advanced solid tumors |
| title_full_unstemmed | A phase Ia study of a novel anti-HER2 antibody–drug conjugate GQ1001 in patients with previously treated HER2 positive advanced solid tumors |
| title_short | A phase Ia study of a novel anti-HER2 antibody–drug conjugate GQ1001 in patients with previously treated HER2 positive advanced solid tumors |
| title_sort | phase ia study of a novel anti her2 antibody drug conjugate gq1001 in patients with previously treated her2 positive advanced solid tumors |
| topic | Antibody–drug conjugate GQ1001 HER2 Solid tumors Dose escalation |
| url | https://doi.org/10.1186/s12967-024-05985-z |
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