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Background <p>Claudin18.2 is a promising therapeutic target expressed in various solid tumors, particularly gastric cancer. IBI389 is a novel anti-Claudin18.2 × CD3 bispecific antibody designed to engage T cells by binding CD3 and Claudin18.2, thereby induce immune synapse formation. Herein, we report preliminary results from a phase I study to evaluate safety and efficacy of IBI389 in patients with advanced solid tumors.</p> Methods <p>Eligible patients with advanced solid tumors refractory to standard treatments were enrolled. The dose escalation of IBI389 monotherapy used intra-patient dose escalation with accelerated titration (0.003/0.01/0.03/0.1/0.3/1&#xa0;µg/kg Q2W) and the classical 3 + 3 design (3/5/10/30/100/300/600&#xa0;µg/kg Q3W). Selected dose levels were expanded in patients with advanced gastric/gastroesophageal junction cancer (GC/GEJC) and pancreatic ductal adenocarcinoma. The primary objective was safety. Secondary objective was efficacy assessed by investigator per RECIST v1.1 including objective response rate (ORR) and disease control rate (DCR).</p> Results <p>A total of 121 patients with solid tumors were enrolled, comprising 23 gastric cancer, 14 gastroesophageal junction cancer, 73 pancreatic adenocarcinoma, and 11 other gastrointestinal solid tumors. No dose-limiting toxicity (DLT) was observed during escalation, and the maximum tolerated dose was not reached. Treatment-related adverse events (TRAEs) occurred in 120 patients (99.2%), with the most common grade ≥ 3 TRAE being gamma-glutamyltransferase increased (21.5%) and lymphocytopenia (14.0%) and other grade ≥ 3 TRAEs were ≤ 5%. Cytokine release syndrome (CRS) related adverse events occurred in 72 patients (59.5%), all grades 1–2 except one grade 3 event. No neurotoxicity or treatment-related deaths were observed. Among 37 patients with GC/GEJC, 27 of them expressing Claudin18.2 at levels of 2 + or 3 + ≥ 10%. In this subgroup, the ORR was 22.2% (6/27; 95% CI, 8.6–42.3) and DCR was 74.1% (20/27; 95% CI, 53.7–88.9). Median progression-free survival (PFS) was 4.3&#xa0;months (95% CI, 2.7–7.2), and median overall survival (OS) was 10.3&#xa0;months (95% CI, 6.6–not calculable). IBI389 exhibited dose-proportional exposure, with a terminal half-life (t<sub>1/2</sub>) ranging from 86.3 to 175.8&#xa0;h.</p> Conclusions <p>IBI389 showed manageable safety profiles in patients with advanced solid tumors and preliminary efficacy in Claudin18.2-positive patients with GC/GEJC.</p> Trial registration <p><a href="http://www.ClinicalTrials.gov">www.ClinicalTrials.gov</a>. NCT05164458 (December 20, 2021).</p>

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Safety and preliminary efficacy results of IBI389, an anti-Claudin18.2×CD3 bispecific antibody, in patients with solid tumors and gastric or gastro-esophageal tumors: a phase 1 dose escalation and expansion study

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  • 发表日期：

    2026年1月16日

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  • Xiaoyu Li,
  • Ruihong Dai,
  • Qi Xu,
  • Zengqing Guo,
  • Changlu Hu,
  • Yuping Sun,
  • Zuoxing Niu,
  • Jihui Hao,
  • Mingjun Zhang,
  • Guanghai Dai,
  • Dong Hua,
  • Yueyin Pan,
  • Xin Wang,
  • Shuqing Wei,
  • Xiaobing Chen,
  • Qian Wu,
  • Yulong Zhang,
  • Hui Zhou,
  • Jieer Ying,
  • Li Zheng,
  • Feng Bi

摘要

Background

Claudin18.2 is a promising therapeutic target expressed in various solid tumors, particularly gastric cancer. IBI389 is a novel anti-Claudin18.2 × CD3 bispecific antibody designed to engage T cells by binding CD3 and Claudin18.2, thereby induce immune synapse formation. Herein, we report preliminary results from a phase I study to evaluate safety and efficacy of IBI389 in patients with advanced solid tumors.

Methods

Eligible patients with advanced solid tumors refractory to standard treatments were enrolled. The dose escalation of IBI389 monotherapy used intra-patient dose escalation with accelerated titration (0.003/0.01/0.03/0.1/0.3/1 µg/kg Q2W) and the classical 3 + 3 design (3/5/10/30/100/300/600 µg/kg Q3W). Selected dose levels were expanded in patients with advanced gastric/gastroesophageal junction cancer (GC/GEJC) and pancreatic ductal adenocarcinoma. The primary objective was safety. Secondary objective was efficacy assessed by investigator per RECIST v1.1 including objective response rate (ORR) and disease control rate (DCR).

Results

A total of 121 patients with solid tumors were enrolled, comprising 23 gastric cancer, 14 gastroesophageal junction cancer, 73 pancreatic adenocarcinoma, and 11 other gastrointestinal solid tumors. No dose-limiting toxicity (DLT) was observed during escalation, and the maximum tolerated dose was not reached. Treatment-related adverse events (TRAEs) occurred in 120 patients (99.2%), with the most common grade ≥ 3 TRAE being gamma-glutamyltransferase increased (21.5%) and lymphocytopenia (14.0%) and other grade ≥ 3 TRAEs were ≤ 5%. Cytokine release syndrome (CRS) related adverse events occurred in 72 patients (59.5%), all grades 1–2 except one grade 3 event. No neurotoxicity or treatment-related deaths were observed. Among 37 patients with GC/GEJC, 27 of them expressing Claudin18.2 at levels of 2 + or 3 + ≥ 10%. In this subgroup, the ORR was 22.2% (6/27; 95% CI, 8.6–42.3) and DCR was 74.1% (20/27; 95% CI, 53.7–88.9). Median progression-free survival (PFS) was 4.3 months (95% CI, 2.7–7.2), and median overall survival (OS) was 10.3 months (95% CI, 6.6–not calculable). IBI389 exhibited dose-proportional exposure, with a terminal half-life (t1/2) ranging from 86.3 to 175.8 h.

Conclusions

IBI389 showed manageable safety profiles in patients with advanced solid tumors and preliminary efficacy in Claudin18.2-positive patients with GC/GEJC.

Trial registration

www.ClinicalTrials.gov. NCT05164458 (December 20, 2021).