First-line osemitamab (TST001) plus nivolumab and capox for advanced g/GEJ cancer (TranStar102): Results of cohort G from a phase I/IIa study.

4048 Background: TST001 is a humanized monoclonal antibody with improved affinity to claudin 18.2 (CLDN18.2) and enhanced ADCC activity. In vivoanti-tumor activity of TST001 plus an anti-PD-1 antibody and chemotherapy is significantly stronger than chemotherapy plus anti-PD-1 antibody or chemotherapy plus anti-CLDN18.2 antibody, regardless of the CPS PDL1 levels. Promising efficacy of osemitamab plus CAPOX chemotherapy as 1 st line treatment of G/GEJ cancer has been observed in cohort C of TranStar102, making the triple combination of TST001, nivolumab and CAPOX an attractive combination to explore. Methods: Cohort G from TranStar102 (NCT04495296) is designed to evaluate the safety and preliminary efficacy of TST001 (at 2 doses: 3mg/kg or 6mg/kg Q3W) plus nivolumab and CAPOX as 1 st line treatment in patients with G/GEJ cancer, with a safety lead-in and expansion phase. 40 patients were planned to be enrolled in each dose cohort. Eligible patients include HER2 negative or unknown, unresectable locally advanced or metastatic G/GEJ cancer, regardless of CLDN18.2 or PD-L1 expression. CLDN18.2 and PD-L1 status are analyzed retrospectively using IHC 14G11 LDT assay and PD-L1 IHC 28-8 pharmDx. Results: As of Jan 19, 2024, 82 patients have been dosed with a median follow-up of 9.7 months, 40 patients at 3mg/kg, 42 patients at 6mg/kg. All patients experienced treatment-related adverse events (TRAEs). The most common TRAEs were hypoalbuminemia (67.1%), nausea (63.4%), and vomiting (59.8%). The incidence of nausea (69% vs 57.5%) and hypoalbuminaemia (76.2% vs 57.5%) was higher at 6mg/kg than 3mg/kg. Most of the TRAEs are grade 1 or 2. The most common TRAE grade 3 or higher were neutrophil decreased (n=10), platelet count decreased (n=8), nausea (2 at 3mg/kg, 1 at 6mg/kg) and vomiting (2 at 3mg/kg). No new safety signal was detected when nivolumab was added to TST001 in combination with chemotherapy. 79 patients had measurable disease at baseline including 25 CLDN18.2 negative patients. 51/79 patients had partial response as of cut-off date, out of which 45 were confirmed (ORR 57%), with no significant difference between the 2 dose levels. 17 patients had stable disease. The disease control rate (DCR) was 91.9% in all patients across CLDN18.2 expression levels and CPS PD-L1 levels. The progression-free survival (PFS) and duration of response (DoR) are immature and need longer follow-up. Conclusions: Preliminary data indicate that the combination of TST001 6mg/kg Q3W plus nivolumab and CAPOX for the 1 st line treatment of patients with G/GEJ cancer is safe and well tolerated with encouraging preliminary anti-tumor activities. Updated clinical data, including PFS and DoR will be reported at the time of the conference. Clinical trial information: NCT04495296 .