A multicenter, phase 1 study of AB011, a recombinant humanized anti-CLDN18.2 monoclonal antibody, as monotherapy and combined with capecitabine and oxaliplatin (CAPOX) in patients with advanced solid tumors.

391 Background: Claudin18.2 (CLDN18.2) is normally confined in tight junction of the gastric mucosa, but is also often expressed in several cancer types. AB011 is a humanized, anti-CLDN18.2 monoclonal antibody (IgG1), which has shown impressive therapeutic synergy between AB011 and cytotoxic agents in preclinical research. Here we report the preliminary data on AB011 both as monotherapy and combined with CAPOX in patients with advanced solid tumors (AB011-ST-01, NCT04400383). Methods: The primary objectives were to evaluate the safety and preliminary efficacy of AB011 as monotherapy (Part 1) and AB011 plus chemotherapy (Part 2) in advanced solid tumors. In part 1, patients with CLDN18.2 positive, treatment-refractory advanced gastric cancer/gastroesophageal junction adenocarcinoma (GC/GEJA) and pancreatic cancer (PC) were enrolled. AB011 dose levels from 1mg/kg to 30mg/kg were explored using i3 + 3 design in dose-escalation stage, and in dose-expansion stage, 20mg/kg and 30mg/kg were further evaluated. In part 2, patients with advanced GC/GEJA were eligible if they had measurable lesions and positive CLDN18.2 expression (IHC 2+/3+ ≥ 40%). AB011 dose levels of 20mg/kg and 30mg/kg were explored using 3 + 3 design. Data are reported as of Sep06, 2022. Results: [Part 1] From Aug 2020 to Aug 2021, 14 pts were treated with AB011 at 1, 3, 10, 20 and 30mg/kg in dose-escalation stage, and 21 pts in dose-expansion stage (10 at 20mg/kg and 11 at 30mg/kg). 77.1% had received ≥ 2 prior lines of treatment. 12/26 (46.2%) GC/GEJ had ≥ 3 metastatic organs with 15 (57.7%) had peritoneal dissemination; 6/9 (66.7%) PC had ≥ 2 metastatic organs. Most treatment-related adverse events (TRAEs) were grade 1-2. 8 pts experienced grade 3 TRAEs (3 in 20mg/kg and 5 in 30mg/kg). One DLT (grade 3 dyspnea) occurred in 30mg/kg group. Among 20 pts with measurable disease and at least one tumor assessment, disease control was observed in 12pts, and 1 GC (30mg/kg) without target lesions assessed to be CR. [Part 2] From September 2021 to July 2022, 24 pts with GC/GEJA were treated with AB011 plus CAPOX (13 pts in 20mg/kg, 11 pts in 30mg/kg). 45.8% had ≥3 metastatic organs, with 29.2% had peritoneal dissemination. 14 pts experienced grade ≥3 TRAEs, incl. neutrophil count decreased, anemia, hypoalbuminemia, nausea and vomiting. No pts experienced DLT, or TRAEs leading to treatment discontinuation or death. Among 23 pts who had at least one tumor assessment by the data cut-off, 8/13 (61.5%) in 20mg/kg group and 7/10 (70%) in 30mg/kg group achieved PR. The ORR and DCR were 65.2% and 100% respectively. Conclusions: These results indicate that AB011, either in monotherapy or combined with chemotherapy, had a manageable safety profile and encouraging efficacy in CLDND18.2 positive advanced GC/GEJA and PC. Clinical trial information: NCT04400383 .