The Lancet. Oncology · 2026
SHR-A2102, a nectin-4 directed antibody-drug conjugate, in patients with pretreated advanced solid tumours: a multicentre, single-arm, phase 1 trial.
СтатьяКлиническое исследование I фазыМногоцентровое исследованиеНазвание и аннотация: Перевод в очереди
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Zhong Runbo, Hong Huangming, Yan Min, Wang Qiming, Zhang Yan, Lan Qiongyu, Luo Yongzhong, Zhang Ling, Xu Haipeng, Guo Sanxing, Guo Wei, Ma Jie, Zhang Longzhen, Wu Lin, Liu Zhigang, He Wei, Sun Yubei, Chen Kai, Huang Jiangqiong, Han Guang, Nian Weiqi, Zhang Ming, Ren Shengxiang, Qiao Rong, Li Xiang, Yu Meijing, Hu Jin, Huang Yanhua, Song Li, Shi Wei, Zhong Hua
Аннотация
BACKGROUND: SHR-A2102 is a new antibody-drug conjugate consisting of a fully human nectin-4-directed monoclonal antibody bound to a topoisomerase I inhibitor payload via a cleavable linker. We did a phase 1 trial to evaluate the safety, preliminary activity, and pharmacokinetics of SHR-A2102 in advanced solid tumours.
METHODS: This multicentre, single-arm, phase 1 trial was done at 39 hospitals in China and included dose-escalation (Bayesian Optimal Interval design), pharmacokinetic-expansion, and efficacy-expansion stages. Eligible patients were aged at least 18 years, had unresectable, locally advanced or metastatic solid tumours that had progressed after, were intolerant to, or had no available standard therapy, and had an Eastern Cooperative Oncology Group performance status score of 0 or 1. Patients received SHR-A2102 intravenously at doses of 2-10 mg/kg once every 3 weeks. The primary endpoints were safety, dose-limiting toxicity, maximum tolerated dose, and recommended phase 2 dose. All patients who received at least one dose of SHR-A2102 were included in the safety and activity analyses. This trial is registered at ClinicalTrials.gov (NCT05701709) and is ongoing.
FINDINGS: Between April 17, 2023 and Feb 20, 2025, 395 patients (median age 59 years [IQR 53-66]; 239 [61%] male and 156 [39%] female; 395 [100%] Chinese) were enrolled and treated across study stages, including 197 with non-small cell lung cancer, 32 with hormone receptor-positive, HER2-negative breast cancer, 36 with triple-negative breast cancer, 77 with oesophageal squamous cell carcinoma, 26 with head-and-neck squamous-cell carcinoma, and 27 with other solid tumours. As of data cutoff (June 20, 2025), the median follow-up was 7·2 months (IQR 4·7-9·7). Based on data from the dose-escalation stage, 6 mg/kg (n=10) and 8 mg/kg (n=11) were selected for pharmacokinetic expansion. During dose escalation, one dose-limiting toxicity was reported at 10 mg/kg (grade 4 decreased platelet count); maximum tolerated dose was not reached. Grade 3-4 treatment-related adverse events were reported in 212 (54%) of 395 patients, with the most common being decreased neutrophil count (118 [30%]), decreased white-blood-cell count (75 [19%]), and anaemia (69 [17%]). Treatment-related serious adverse events were reported in 98 (25%) patients with the most common being pneumonia (21 [5%]). Treatment-related deaths occurred in two (<1%) patients (pulmonary embolism and pneumonia).
INTERPRETATION: SHR-A2102 demonstrated a safety profile consistent with its topoisomerase I inhibitor payload and showed promising activity in patients with various advanced solid tumours who had previously received anti-cancer treatment. A range of active dose was identified in various tumour types. Several trials are ongoing to evaluate SHR-A2102, either as monotherapy or in combination, in advanced solid tumours.
FUNDING: Jiangsu Hengrui Pharmaceuticals.
METHODS: This multicentre, single-arm, phase 1 trial was done at 39 hospitals in China and included dose-escalation (Bayesian Optimal Interval design), pharmacokinetic-expansion, and efficacy-expansion stages. Eligible patients were aged at least 18 years, had unresectable, locally advanced or metastatic solid tumours that had progressed after, were intolerant to, or had no available standard therapy, and had an Eastern Cooperative Oncology Group performance status score of 0 or 1. Patients received SHR-A2102 intravenously at doses of 2-10 mg/kg once every 3 weeks. The primary endpoints were safety, dose-limiting toxicity, maximum tolerated dose, and recommended phase 2 dose. All patients who received at least one dose of SHR-A2102 were included in the safety and activity analyses. This trial is registered at ClinicalTrials.gov (NCT05701709) and is ongoing.
FINDINGS: Between April 17, 2023 and Feb 20, 2025, 395 patients (median age 59 years [IQR 53-66]; 239 [61%] male and 156 [39%] female; 395 [100%] Chinese) were enrolled and treated across study stages, including 197 with non-small cell lung cancer, 32 with hormone receptor-positive, HER2-negative breast cancer, 36 with triple-negative breast cancer, 77 with oesophageal squamous cell carcinoma, 26 with head-and-neck squamous-cell carcinoma, and 27 with other solid tumours. As of data cutoff (June 20, 2025), the median follow-up was 7·2 months (IQR 4·7-9·7). Based on data from the dose-escalation stage, 6 mg/kg (n=10) and 8 mg/kg (n=11) were selected for pharmacokinetic expansion. During dose escalation, one dose-limiting toxicity was reported at 10 mg/kg (grade 4 decreased platelet count); maximum tolerated dose was not reached. Grade 3-4 treatment-related adverse events were reported in 212 (54%) of 395 patients, with the most common being decreased neutrophil count (118 [30%]), decreased white-blood-cell count (75 [19%]), and anaemia (69 [17%]). Treatment-related serious adverse events were reported in 98 (25%) patients with the most common being pneumonia (21 [5%]). Treatment-related deaths occurred in two (<1%) patients (pulmonary embolism and pneumonia).
INTERPRETATION: SHR-A2102 demonstrated a safety profile consistent with its topoisomerase I inhibitor payload and showed promising activity in patients with various advanced solid tumours who had previously received anti-cancer treatment. A range of active dose was identified in various tumour types. Several trials are ongoing to evaluate SHR-A2102, either as monotherapy or in combination, in advanced solid tumours.
FUNDING: Jiangsu Hengrui Pharmaceuticals.