The first-in-class bispecific antibody IBI318 (LY3434172) targeting PD-1 and PD-L1 in patients with advanced tumors: a phase Ia/Ib study
Abstract Background There is an unmet clinical need to enhance the response rate and safety of anti-PD-1/PD-L1-based cancer immunotherapy (IO). Herein, we presented the clinical study of IBI318 (LY3434172), a first-in-class bispecific antibody (bsAb) targeting PD-1 and PD-L1, in patients with advanc...
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| Format: | Article |
| Language: | English |
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BMC
2024-11-01
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| Series: | Journal of Hematology & Oncology |
| Online Access: | https://doi.org/10.1186/s13045-024-01644-4 |
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| author | Dan-Yun Ruan Xiao-Li Wei Fu-Rong Liu Xi-Chun Hu Jian Zhang Dong-Mei Ji Ding-Zhi Huang Yan-Qiu Zhao Hong-Min Pan Wang-Jun Liao Kun-Yu Yang Nong Xu Xiao-Xiao Lu Yu-Ling Chen Wen Zhang Hui Zhou Hong-Yun Zhao Rui-Hua Xu |
| author_facet | Dan-Yun Ruan Xiao-Li Wei Fu-Rong Liu Xi-Chun Hu Jian Zhang Dong-Mei Ji Ding-Zhi Huang Yan-Qiu Zhao Hong-Min Pan Wang-Jun Liao Kun-Yu Yang Nong Xu Xiao-Xiao Lu Yu-Ling Chen Wen Zhang Hui Zhou Hong-Yun Zhao Rui-Hua Xu |
| author_sort | Dan-Yun Ruan |
| collection | DOAJ |
| description | Abstract Background There is an unmet clinical need to enhance the response rate and safety of anti-PD-1/PD-L1-based cancer immunotherapy (IO). Herein, we presented the clinical study of IBI318 (LY3434172), a first-in-class bispecific antibody (bsAb) targeting PD-1 and PD-L1, in patients with advanced tumors. Methods In this open-label, multicenter Phase Ia/Ib study of IBI318, the Phase Ia involved dose escalation and a safety dose expansion, while the Phase Ib focused on preliminary safety and efficacy evaluation in non-small cell lung cancer (NSCLC) and nasopharyngeal carcinoma (NPC). In Phase Ia, patients with advanced tumors received IBI318 doses ranging from 0.3 to 1200 mg every two weeks (Q2W) to determine the recommended Phase 2 dose (RP2D). In Phase Ib, NSCLC or NPC patients from five cohorts with varying treatment histories received IBI318 at the RP2D. The primary endpoint was safety and the secondary endpoints included efficacy assessed by investigators according to RECIST v1.1, pharmacokinetics, immunogenicity, and pharmacodynamics. Results From February 11, 2019, to January 25, 2022, a total of 103 eligible patients were enrolled (Phase Ia, n = 55; Phase Ib, n = 48). The median follow-up was 10.1 months (range 0.7–28.6). The RP2D was determined to be 300 mg Q2W. Treatment-related adverse events (TRAEs) of any grades occurred in 88 patients (85.4%), while 10 patients (9.7%) experienced grade ≥ 3 TRAEs. The objective response rate (ORR) was 15.5% and the disease control rate (DCR) was 49.5% in all patients. In Phase Ib, the confirmed ORR was 45.5% in treatment-naïve NSCLC patients and 30.0% in IO-naïve NPC patients who had failed or were intolerant to platinum-based treatments. Conclusions IBI318 demonstrated a favorable safety profile and preliminary efficacy in treatment-naïve NSCLC and IO-naïve NPC patients. Further clinical studies are needed to assess the full therapeutic potential of PD-1/PD-L1 dual inhibition with bsAbs. |
| format | Article |
| id | doaj-art-a9a7ec4c1b9647f89eb73df41a05bd37 |
| institution | Kabale University |
| issn | 1756-8722 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Hematology & Oncology |
| spelling | doaj-art-a9a7ec4c1b9647f89eb73df41a05bd372024-12-01T12:41:12ZengBMCJournal of Hematology & Oncology1756-87222024-11-0117111210.1186/s13045-024-01644-4The first-in-class bispecific antibody IBI318 (LY3434172) targeting PD-1 and PD-L1 in patients with advanced tumors: a phase Ia/Ib studyDan-Yun Ruan0Xiao-Li Wei1Fu-Rong Liu2Xi-Chun Hu3Jian Zhang4Dong-Mei Ji5Ding-Zhi Huang6Yan-Qiu Zhao7Hong-Min Pan8Wang-Jun Liao9Kun-Yu Yang10Nong Xu11Xiao-Xiao Lu12Yu-Ling Chen13Wen Zhang14Hui Zhou15Hong-Yun Zhao16Rui-Hua Xu17Department of Clinical Research, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen UniversityDepartment of Medical Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Sun Yat-Sen UniversityDepartment of Clinical Research, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen UniversityDepartment of Oncology, Shanghai Medical College, Fudan UniversityDepartment of Oncology, Shanghai Medical College, Fudan UniversityDepartment of Oncology, Shanghai Medical College, Fudan UniversityDepartment of Thoracic Oncology, Tianjin Medical University Cancer Institute and HospitalDepartment of Oncology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, The Academy of Medical Science, Zhengzhou UniversityMedical Oncology, Sir Run Run Shaw Hospital (SRRSH), affiliated with the Zhejiang University School of MedicineDepartment of Oncology, Nanfang Hospital, Southern Medical UniversityCancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Medical Oncology, The First Affiliated Hospital, College of Medicine, Zhejiang UniversityInnovent Biologics (Suzhou) Co. LtdInnovent Biologics (Suzhou) Co. LtdInnovent Biologics (Suzhou) Co. LtdInnovent Biologics (Suzhou) Co. LtdDepartment of Clinical Research, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen UniversityDepartment of Medical Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Sun Yat-Sen UniversityAbstract Background There is an unmet clinical need to enhance the response rate and safety of anti-PD-1/PD-L1-based cancer immunotherapy (IO). Herein, we presented the clinical study of IBI318 (LY3434172), a first-in-class bispecific antibody (bsAb) targeting PD-1 and PD-L1, in patients with advanced tumors. Methods In this open-label, multicenter Phase Ia/Ib study of IBI318, the Phase Ia involved dose escalation and a safety dose expansion, while the Phase Ib focused on preliminary safety and efficacy evaluation in non-small cell lung cancer (NSCLC) and nasopharyngeal carcinoma (NPC). In Phase Ia, patients with advanced tumors received IBI318 doses ranging from 0.3 to 1200 mg every two weeks (Q2W) to determine the recommended Phase 2 dose (RP2D). In Phase Ib, NSCLC or NPC patients from five cohorts with varying treatment histories received IBI318 at the RP2D. The primary endpoint was safety and the secondary endpoints included efficacy assessed by investigators according to RECIST v1.1, pharmacokinetics, immunogenicity, and pharmacodynamics. Results From February 11, 2019, to January 25, 2022, a total of 103 eligible patients were enrolled (Phase Ia, n = 55; Phase Ib, n = 48). The median follow-up was 10.1 months (range 0.7–28.6). The RP2D was determined to be 300 mg Q2W. Treatment-related adverse events (TRAEs) of any grades occurred in 88 patients (85.4%), while 10 patients (9.7%) experienced grade ≥ 3 TRAEs. The objective response rate (ORR) was 15.5% and the disease control rate (DCR) was 49.5% in all patients. In Phase Ib, the confirmed ORR was 45.5% in treatment-naïve NSCLC patients and 30.0% in IO-naïve NPC patients who had failed or were intolerant to platinum-based treatments. Conclusions IBI318 demonstrated a favorable safety profile and preliminary efficacy in treatment-naïve NSCLC and IO-naïve NPC patients. Further clinical studies are needed to assess the full therapeutic potential of PD-1/PD-L1 dual inhibition with bsAbs.https://doi.org/10.1186/s13045-024-01644-4 |
| spellingShingle | Dan-Yun Ruan Xiao-Li Wei Fu-Rong Liu Xi-Chun Hu Jian Zhang Dong-Mei Ji Ding-Zhi Huang Yan-Qiu Zhao Hong-Min Pan Wang-Jun Liao Kun-Yu Yang Nong Xu Xiao-Xiao Lu Yu-Ling Chen Wen Zhang Hui Zhou Hong-Yun Zhao Rui-Hua Xu The first-in-class bispecific antibody IBI318 (LY3434172) targeting PD-1 and PD-L1 in patients with advanced tumors: a phase Ia/Ib study Journal of Hematology & Oncology |
| title | The first-in-class bispecific antibody IBI318 (LY3434172) targeting PD-1 and PD-L1 in patients with advanced tumors: a phase Ia/Ib study |
| title_full | The first-in-class bispecific antibody IBI318 (LY3434172) targeting PD-1 and PD-L1 in patients with advanced tumors: a phase Ia/Ib study |
| title_fullStr | The first-in-class bispecific antibody IBI318 (LY3434172) targeting PD-1 and PD-L1 in patients with advanced tumors: a phase Ia/Ib study |
| title_full_unstemmed | The first-in-class bispecific antibody IBI318 (LY3434172) targeting PD-1 and PD-L1 in patients with advanced tumors: a phase Ia/Ib study |
| title_short | The first-in-class bispecific antibody IBI318 (LY3434172) targeting PD-1 and PD-L1 in patients with advanced tumors: a phase Ia/Ib study |
| title_sort | first in class bispecific antibody ibi318 ly3434172 targeting pd 1 and pd l1 in patients with advanced tumors a phase ia ib study |
| url | https://doi.org/10.1186/s13045-024-01644-4 |
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