An open-label, multicenter, phase I study of ATG-022 in patients with advanced/metastatic solid tumors (CLINCH).

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3032 Background: Claudin 18.2 (CLDN 18.2) is a tumor associated antigen broadly expressed in gastric, pancreatic, and other solid tumors. ATG-022 is an antibody drug conjugate (ADC), consisting of a humanized monoclonal antibody that binds to CLDN 18.2 with high affinity of sub-nM grade and a conjugated linker-payload vc-MMAE. ATG-022 has displayed promising tumor growth inhibition activity both in vitro and in vivo. Methods: CLINCH is a phase I, multi-center, open-label, dose-finding study (NCT05718895) of ATG-022 in patients with advanced solid tumours. The study design includes a dose escalation phase, enrolling subjects with advanced/metastatic solid tumors, regardless of CLDN 18.2 expression, and a dose expansion phase which will enroll select advanced/metastatic solid tumors with CLDN 18.2-positive expression at the defined maximum tolerated dose and/or recommended Phase 2 dose to further evaluate the safety, tolerability, and efficacy of ATG-022. Other endpoints include pharmacokinetics (PK) and exploratory biomarkers of drug activity. In the dose escalation phase, ATG-022 is administered intravenously every 3 weeks (Q3W) at the starting dose of 0.3 mg/kg, followed by 0.9, 1.8, 2.4, 3.0, and 3.6 mg/kg Q3W using a modified 3+3 dose-escalation design. Efficacy assessments are evaluated per RECIST1.1 criteria. Results: As of 9 Oct 2023, 10 patients (pts) with advanced solid tumors have been enrolled to receive ATG-022 at a dose from 0.3 to 2.4 mg/kg. Median age was 59 years. Baseline ECOG scores were 0 (0 pts) and 1 (10 pts); 8 pts had stage IV disease. Three pts had received more than 3 prior lines of systemic therapy. Eight pts (80%) had ≥ 1 TRAEs; 1 pt (10%) had ≥ 1 Serious TRAEs; 3 (30%) pts had grade ≥ 3 TRAEs. The most common grade ≥ 3 TRAEs included nausea (30%), vomiting (30%) and decreased appetite (30%). No DLT was reported among the current dose levels. Among 7 pts with gastric cancer, 3 pts are confirmed to be CLDN 18.2 positive. One of these pts has maintained stable disease with tumor shrinkage for more than 6 months (treatment ongoing) at a dose of 0.9 mg/kg, demonstrating tolerability of ATG-022. One PR was observed in a gastric cancer pt (CLDN 18.2 expression to be determined) at the dosage of 1.8 mg/kg. It was noteworthy that a CR was seen in a gastric cancer pt dosed at 2.4 mg/kg, with negative CLDN 18.2 expression. PK analysis of ATG-022 from 0.3 to 2.4 mg/kg revealed that the exposure of total antibody, MMAE and ADC drug is increased as dose increased. No accumulation of ATG-022 was observed. Conclusions: ATG-022 demonstrated preliminary anti-tumor activity, tolerability, safety, as well as comparable PK properties at current dose levels. The high affinity of sub-nM grade of ATG-022 in pts with low CLDN 18.2 expression needs further investigation. The dose escalation is ongoing and updated data will be presented. Clinical trial information: NCT05718895 .