Safety, tolerability, pharmacokinetics and preliminary efficacy of MIL93, an anti-Claudin18.2 monoclonal antibody, in patients with advanced solid tumors: A phase 1 clinical study.

Abstract

3086 Background: Claudin18.2 (CLDN18.2) is specifically expressed in the tight junction of gastric epithelial cells, and has been identified as a promising target in gastric and pancreatic cancer as well as several other malignancies. MIL93 is a humanized IgG1 monoclonal antibody targeting CLDN18.2. From January 2021, we started a multicenter, dose escalation and expansion phase 1 study of MIL93, for the treatment of patients with advanced solid tumors (Protocol number MIL93-CT101, Beijing Mabworks Biotech Co. Ltd.) at 6 clinical study sites in China. Currently the study is still ongoing. Methods: We already enrolled 13 pts aged 18 years or older with advanced solid tumors whose disease had progressed after standard systemic treatments. Pts were required to have measurable lesion as per RECIST v1.1; ECOG PS score of 0-1 and adequate organ functions. In the dose escalation phase, 6 dose levels (0.3mg/kg, 1mg/kg, 3mg/kg, 10mg/kg, 20mg/kg and 30mg/kg, Q3W) of MIL93 were planned for assessment. Accelerated titration was adopted for the first 2 dose levels, and the 3+3 design was used afterwards. In the dose expansion phase, pts with CLDN18.2-positive cancers received the selected RP2D. The primary objectives were the safety and tolerability, dose limiting toxicities (DLTs) and maximum tolerated dose (MTD) of MIL93. Secondary objectives included pharmacokinetics, immunogenicity and preliminary efficacy. Results: At the data cut-off date (February 14, 2022), 13 pts were enrolled between April 23, 2021 and February 9, 2022. MIL93 was well-tolerated for the dosages tested (0.3mg/kg through 20mg/kg Q3W) as no DLTs were observed, and dose escalation was ongoing at 30mg/kg. In particular, Grade 3 nausea and vomiting occurred in 2 cases in the third dose group, so preventive antiemetic treatment was given from the fourth dose group. 9 pts (69.2%) experienced at least one treatment-emergent adverse event (TEAE) with no Grade 4 or Grade 5 AEs. The most common treatment-related adverse events (TRAEs) occurring in ≥10% of pts were nausea (46.2%), vomiting (46.2%), fatigue (15.4%), anemia (15.4%). Serious adverse events (SAEs) were observed in 3 (23.1%) pts, and MIL93-related SAEs occurred in 1 pt (7.7%, Grade 3 nausea). Among the 10 pts who had at least one post-treatment radiological evaluation, 1 pt with CLDN18.2-positive gastric cancer achieved PR and 3 pts had SD, including 1 case of gastric cancer, 1 case of gastroesophageal junction cancer and 1 case of gallbladder cancer. Conclusions: MIL93 had a favorable safety profile with no DLTs observed through 20mg/kg Q3W. Pts with CLDN18.2-positive gastric cancer responded to the treatment. Dose escalation and expansion in selected tumor types is currently underway. Clinical trial information: NCT04671875.