I-Mab (IMAB) announced that an expanded Phase 1 monotherapy study of givastomig, a Claudin 18.2 x 4-1BB bispecific antibody, showed promising results in patients with gastric cancers expressing varying levels of Claudin 18.2. The recommended Phase 2 dosage for givastomig is set at 8-12 mg/kg, and it showed good tolerability even at the highest study doses. An ongoing Phase 1b study is evaluating givastomig in combination with standard-of-care treatment (nivolumab and chemotherapy (FOLFOX)) for front-line gastric cancer patients.
Key outcomes from the Phase 1 monotherapy study indicated that out of 43 patients with CLDN18.2+ gastric cancers treated with givastomig doses ranging from 5 to 18 mg/kg, seven patients experienced partial responses (one at 5 mg/kg, one at 8 mg/kg, four at 12 mg/kg, and one at 18 mg/kg), translating to an objective response rate (ORR) of 16.3% (7/43 patients). Notably, five out of these seven patients (71%) had previously been treated with a checkpoint inhibitor. Stable disease (SD) was observed in 14 patients, resulting in a disease control rate (DCR) of 48.8% (21/43 patients).
No dose-limiting toxicity was identified up to doses of 15 mg/kg administered bi-weekly (Q2W) and 18 mg/kg administered tri-weekly (Q3W), and a maximum tolerated dose (MTD) was not established. The most common treatment-related adverse events (TRAEs) were primarily of grade 1 or 2 severity.
Givastomig also demonstrated linear pharmacokinetics at doses equal to or greater than 5 mg/kg and exhibited a dose-dependent increase in soluble 4-1BB levels, stabilizing at doses between 8 mg/kg and 18 mg/kg.
