I-Mab publishes givastomig monotherapy data in Clinical Cancer Research

I-Mab (IMAB) announced publication of the first-in-human monotherapy data for givastomig, a bispecific Claudin 18.2 x 4-1BB antibody, in Clinical Cancer Research, a journal of the American Association for Cancer Research, and a clinical oncology publication. The CCR paper details promising clinical data showing that givastomig monotherapy achieved an objective response rate of 16% in heavily pretreated Claudin 18.2-positive gastric cancer patients. The CCR paper represents the first peer-reviewed manuscript publication of the Phase 1 monotherapy study of givastomig in heavily pre-treated solid tumor patients, after initial presentation of these data in poster form at the European Society of Medical Oncology Congresses in 2023 and 2024. The study evaluated a total of 75 patients with gastric cancers or other solid tumors, including 43 efficacy-evaluable patients with CLDN18.2-positive advanced or metastatic gastroesophageal carcinoma. Claudin 18.2 expression in responders ranged from 11% to 100%, demonstrating the activity of givastomig in tumors with low levels of Claudin 18.2 expression. After the data cutoff, two additional patients were enrolled in the monotherapy study, resulting in an additional confirmed partial response, leading to an increased ORR of 18%. The company anticipates sharing an updated monotherapy data set on the 45 patients in the fourth quarter of 2025 at a major medical meeting. Monotherapy data indicate that givastomig is well tolerated and demonstrates single-agent activity in heavily pretreated patients. These findings support its development in combination with standard immunochemotherapy as a first line treatment for gastric cancers. Data from the ongoing dose escalation combination study will be presented at a Mini Oral presentation at the ESMO Gastrointestinal Cancers Congress 2025 on July 2 in Barcelona, Spain. A total of 75 patients received givastomig across nine sequential dose levels between 0.1 and 18 mg/kg. The 75 patients were comprised of 56 subjects from the United States and 19 subjects from China. Patients were heavily pretreated, with a median of three prior lines of therapy. 75% of patients were CLDN18.2-positive, by the trial definition. Of the 43 efficacy-evaluable patients with CLDN18.2-positive advanced or metastatic GEC who received givastomig monotherapy at doses ranging from 5 to 18 mg/kg, PRs were observed in seven patients with an ORR of 16% for single agent givastomig. Five of the seven patients who had achieved a PR had previously received a checkpoint inhibitor. Stable disease was reported in 14 patients, which resulted in a disease control rate of 49%. No dose-limiting toxicity was reported up to 15 mg/kg dosed every two weeks, and 18 mg/kg dosed every three weeks, and a maximum tolerated dose was not identified The most common treatment-related adverse events were mainly Grade 1 or 2. Givastomig exhibited linear pharmacokinetics at doses of 5 mg/kg, and showed a dose-dependent increase in soluble 4-1BB levels, reaching a plateau at doses ranging from 8 to 18 mg/kg. CLDN18.2 expression in responders ranged from 11% to 100%.