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First-in-human phase I/Ib study of QL1706 (PSB205), a bifunctional PD1/CTLA4 dual blocker, in patients with advanced solid tumors.
Zhao, Yuanyuan; Ma, Yuxiang; Zang, Aimin; Cheng, Ying; Zhang, Yiping; Wang, Xiangcai; Chen, Zhendong; Qu, Song; He, Jianbo; Chen, Chuanben; Jin, Chuan; Zhu, Dongyuan; Li, Qingshan; Liu, Xianling; Su, Wuyun; Ba, Yi; Hao, Yanrong; Chen, Junmin; Zhang, Guoping; Qu, Shenhong; Li, Yong; Feng, Weineng; Yang, Mengxiang; Liu, Baorui; Ouyang, Weiwei; Liang, Jin; Yu, Zhuang; Kang, Xiaoyan; Xue, Shilin; Yang, Guihong; Yan, Wei; Yang, Yingying; Liu, Zhi; Peng, Yufeng; Fanslow, Bill; Huang, Xian; Zhang, Li; Zhao, Hongyun.
Affiliation
  • Zhao Y; Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, No. 651 Dongfeng East Road, Guangzhou, 510060, China
  • Ma Y; Department of Clinical Research, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, No. 651 Dongfeng East Road, Guangzhou, 510060, Chin
  • Zang A; Department of Medical Oncology, Affiliated Hospital of Hebei University, Baoding, 071000, China.
  • Cheng Y; Department of Thoracic Oncology, Jilin Cancer Hospital, Changchun, 130012, China.
  • Zhang Y; The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, 310022, Zhejiang, China.
  • Wang X; Department of Oncology, First Affiliated Hospital of Gannan Medical University, Ganzhou, 341001, China.
  • Chen Z; Department of Medical Oncology, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230093, China.
  • Qu S; Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Cancer Institute of Guangxi, Nanning, 530021, Guangxi, China.
  • He J; Department of Medical Oncology of Respiratory, Guangxi Medical University Cancer Hospital, Cancer Institute of Guangxi, Nanning, 530021, Guangxi, China.
  • Chen C; Department of Head and Neck Radiation Oncology, Fujian Cancer Hospital, Fuzhou, 350000, China.
  • Jin C; Department of Medical Oncology, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, 510095, China.
  • Zhu D; Rare Tumors Department, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, China.
  • Li Q; Department of Oncology, Affiliated Hospital of Chengde Medical University, Chengde, 067000, China.
  • Liu X; Department of Oncology, Second Xiangya Hospital, Central South University, Changsha, 410011, China.
  • Su W; Department of Medical Oncology, Affiliated Hospital of Inner Mongolia Medical University, Huhhot, 010050, Inner Mongolia, China.
  • Ba Y; Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China.
  • Hao Y; Department of Oncology, Clinical Oncology Center, The People's Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, Nanning, 530021, China.
  • Chen J; Department of Medical Oncology, Hainan General Hospital, Haikou, 570100, China.
  • Zhang G; Department of Medical Oncology, Yuebei People's Hospital, Shaoguan, 512025, China.
  • Qu S; Department of Otolaryngology & Head and Neck, The People's Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, Nanning, 530021, China.
  • Li Y; Department of Medical Oncology, The First Affiliated Hospital of Nanchang University, Nanchang, 330000, China.
  • Feng W; Department of Head and Neck/Thoracic Medical Oncology, The First People's Hospital of Foshan, Foshan City, 528010, China.
  • Yang M; Oncology Department, Liaocheng People's Hospital, Liaocheng, 252004, China.
  • Liu B; The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, Nanjing, 210008, China.
  • Ouyang W; Department of Oncology, The Affiliated Cancer Hospital of Guizhou Medical University, Guiyang, 550001, China.
  • Liang J; Department of Oncology, The First Affiliated Hospital of Kunming Medical University, Kunming, 650032, China.
  • Yu Z; Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, 266003, China.
  • Kang X; Clinical Research Center, Qilu Pharmaceutical Co., Ltd., Jinan, 250000, China.
  • Xue S; Clinical Research Center, Qilu Pharmaceutical Co., Ltd., Jinan, 250000, China.
  • Yang G; Department of Clinical Pharmacology, Qilu Pharmaceutical Co., Ltd., Jinan, 250000, China.
  • Yan W; Sound Biologics, 21720 23rd Drive SE, Suite200, Bothell, WA, 98021, USA.
  • Yang Y; Department of Non-Clinical, Qilu Pharmaceutical Co., Ltd., Jinan, 250001, China.
  • Liu Z; Sound Biologics, 21720 23rd Drive SE, Suite200, Bothell, WA, 98021, USA.
  • Peng Y; Sound Biologics, 21720 23rd Drive SE, Suite200, Bothell, WA, 98021, USA.
  • Fanslow B; Sound Biologics, 21720 23rd Drive SE, Suite200, Bothell, WA, 98021, USA.
  • Huang X; Sound Biologics, 21720 23rd Drive SE, Suite200, Bothell, WA, 98021, USA.
  • Zhang L; Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, No. 651 Dongfeng East Road, Guangzhou, 510060, China
  • Zhao H; Department of Clinical Research, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, No. 651 Dongfeng East Road, Guangzhou, 510060, Chin
J Hematol Oncol ; 16(1): 50, 2023 05 08.
Article in En | MEDLINE | ID: mdl-37158938
BACKGROUND: QL1706 (PSB205) is a single bifunctional MabPair (a novel technical platform) product consisting of two engineered monoclonal antibodies (anti-PD-1 IgG4 and anti-CTLA-4 IgG1), with a shorter elimination half-life (t1/2) for CTLA-4. We report results from a phase I/Ib study of QL1706 in patients with advanced solid tumors who failed standard therapies. METHODS: In the phase I study, QL1706 was administered intravenously once every 3 weeks at one of five doses ranging from 0.3 to 10 mg/kg, and the maximum tolerated dose, recommended phase 2 dose (RP2D), safety, pharmacokinetics (PK), and pharmacodynamics (PD) of QL1706 were investigated. In the phase Ib study, QL1706 was administered at the RP2D intravenously every 3 weeks, and the preliminary efficacies in non-small cell lung cancer (NSCLC), nasopharyngeal carcinoma (NPC), cervical cancer (CC), and other solid tumors were evaluated. RESULTS: Between March 2020 and July 2021, 518 patients with advanced solid tumors were enrolled (phase I, n = 99; phase Ib, n = 419). For all patients, the three most common treatment-related adverse events (TRAEs) were rash (19.7%), hypothyroidism (13.5%), and pruritus (13.3%). The TRAEs and immune-related adverse events (irAEs) of grade ≥ 3 occurred in 16.0% and 8.1% of patients, respectively. In phase I, 2 of 6 patients in the 10mg/kg group experienced dose-limiting toxicities (DLTs) (grade 3 thrombocytopenia and grade 4 immune-mediated nephritis), so the maximum tolerated dose (MTD) was reached at 10 mg/kg. The RP2D was determined to be 5 mg/kg based on comprehensive analysis of tolerability, PK/PD, and efficacy. For all patients who received QL1706 at the RP2D, the objective response rate (ORR) and median duration of response were 16.9% (79/468) and 11.7 months (8.3-not reached [NR]), respectively; and the ORRs were 14.0% (17/121) in NSCLC, 24.5% (27/110) in NPC, 27.3% (15/55) in CC, 7.4% (2/27) in colorectal cancer, 23.1% (6/26) in small cell lung cancer. For immunotherapy-naive patients, QL1706 exhibited promising antitumor activities, especially in NSCLC, NPC, and CC, with ORRs of 24.2%, 38.7%, and 28.3%, respectively. CONCLUSIONS: QL1706 was well tolerated and demonstrated promising antitumor activity in solid tumors, especially in NSCLC, NPC, and CC patients. It is currently being evaluated in randomized phase II (NCT05576272, NCT05179317) and phase III (NCT05446883, NCT05487391) trials. Trial Registration ClinicalTrials.gov Identifier: NCT04296994 and NCT05171790.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Uterine Cervical Neoplasms / Antibodies, Bispecific / Carcinoma, Non-Small-Cell Lung / CTLA-4 Antigen / Nasopharyngeal Carcinoma / Lung Neoplasms / Antineoplastic Agents Type of study: Clinical_trials Limits: Female / Humans Language: En Journal: J Hematol Oncol Journal subject: HEMATOLOGIA / NEOPLASIAS Year: 2023 Document type: Article Affiliation country: China Country of publication: United kingdom

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Uterine Cervical Neoplasms / Antibodies, Bispecific / Carcinoma, Non-Small-Cell Lung / CTLA-4 Antigen / Nasopharyngeal Carcinoma / Lung Neoplasms / Antineoplastic Agents Type of study: Clinical_trials Limits: Female / Humans Language: En Journal: J Hematol Oncol Journal subject: HEMATOLOGIA / NEOPLASIAS Year: 2023 Document type: Article Affiliation country: China Country of publication: United kingdom