Osemitamab in combination with capecitabine and oxaliplatin (CAPOX) as a first line treatment of advanced G/GEJ cancer: Updated data of cohort C from a phase I/IIa, multi-center study (TranStar102/TST001-1002)

4046 Background: Adding a claudin18.2 antibody to a chemotherapy is a clinically validated approach for patients with high CLDN18.2 expressing tumors. TST001 is a best in class differentiated antibody whose improved CLDN18.2 affinity and enhanced antibody-dependent cellular cytotoxicity, leads to anti-tumor activity in low to medium CLDN18.2 expressors gastric cancer cells. Pre-clinical studies also showed that TST001 has stronger tumor regression effects than the IMAB362-analog at the same dose. Methods: The efficacy and safety of osemitamab with CAPOX as 1st line treatment with G/GEJ cancer was explored in a dose escalation and expansion phase 1/2 study in China (Cohort C, NCT04495296). Positive claudin18.2 expression (membranous staining ≥1+ intensity in≥10% of tumor cells) as assessed centrally using the LDT assay was required in the expansion phase only. Results: As of Dec 31, 2022, 64 patients were dosed with osemitamab in combination with CAPOX, 15 patients received osemitamab at doses ranging from 1 to 8 mg/kg Q3W in the dose escalation and 49 patients at 6 mg/kg in the dose expansion. The median follow up was 151 days. Patient characteristics were typical of 1st line G/GEJ cancer, with relatively higher percentage of peritoneal disease (48.4%). Nausea (65.4%), vomiting (46.2%) and hypoalbuminemia (65.4%) were the most common adverse events related to TST001 at dose of 6mg/kg in 52 patients (3 patients in dose escalation and 49 patients in dose expansion), most of them were grade 1 or 2 (only one patient experienced grade 3 nausea and vomiting, and one experienced grade 3 hypoalbuminemia). In the expansion cohort, 40 of the 45 patients with measurable lesions had at least one post-treatment tumor assessment. 27 achieved partial response (PR) of which 21 were confirmed. There was no obvious trend in improved efficacy with higher level of CLDN18.2 expression based on overall response rate (ORR). Progression free survival (PFS) and duration of response (DOR) were still immature. Conclusions: TST001 in combination with CAPOX as first-line treatment for the patients with G/GEJ cancer is safe and encouraging anti-tumor activities have been observed regardless of the CLDN18.2 expression levels above 1+ intensity in >=10% tumor cells per central LDT assay. Updated ORR, mPFS and mDOR will be presented at the time of the congress. Clinical trial information: NCT04495296 .