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

4032 Background: Claudin 18.2 (CLDN18.2) is a clinically validated therapeutic target and has been broadly explored with different modalities in gastric/gastroesophageal (G/GEJ) cancer treatment. Osemitamab is a humanized monoclonal antibody with improved affinity to CLDN18.2, reduced fucosylation and enhanced ADCC activity and has been observed to upregulate PD-L1 expression on CLDN18.2-positive tumor cells. In vivo anti-tumor activity of combination of osemitamab plus an anti-PD-1/PD-L1 antibody and chemotherapies was significantly stronger than any of the doublet combinations, regardless of the PD-L1 CPS levels, making the triple combination of osemitamab, nivolumab and CAPOX an attractive combination to explore. Methods: Cohort G from TranStar102 (NCT04495296, a phase I/II study) was designed to evaluate the safety and preliminary efficacy of osemitamab at two dose levels (3mg/kg or 6mg/kg Q3W) plus nivolumab and CAPOX as the first-line treatment in patients with G/GEJ cancer. 40 patients were planned to be enrolled in each dose level. Key eligible criteria included HER2 negative or unknown, unresectable locally advanced or metastatic G/GEJ cancer, regardless of CLDN18.2 or PD-L1 expression and treatment naïve for advanced disease. The endpoints include safety, efficacy, PK and predictive value of the different levels of CLDN18.2 expression, etc. Results: As of Jan 13, 2025, 82 patients were dosed with osemitamab plus nivolumab and CAPOX (40 at 3mg/kg, 42 at 6mg/kg) with median follow-up of 21.3 months. All patients experienced treatment-related adverse events (TRAEs). The safety profile was similar with the previously presented data (2024 ESMO poster), and the most commonly observed TRAEs were on-target and off-tumor toxicities, such as nausea, vomiting and hypoalbuminemia, and were manageable. 44 out of 82 patients had confirmed partial response and the objective response rate (ORR) was 55.7%. There was a clear trend between anti-tumor efficacy and CLDN18.2 expression, with a confirmed ORR of 68% and median progression-free survival of 16.6 months (95% CI: 5.8, 21.7) for the patients with CPS known and CLDN18.2 high/medium expression (defined as CLDN18.2 membranous staining ≥2+ in ≥40% of tumor cells by immunohistochemistry in the central laboratory) (n=26). By the cut-off date, there were 33 patients in survival follow-up including 12 patients still with ongoing treatment. The median overall survival was 20.4 months (95% CI:15.0, NE) for all the 82 patients. Updated clinical data and details by biomarkers levels will be reported at the time of conference. Conclusions: The updated data indicate that the combination of TST001 plus nivolumab and CAPOX for the first-line treatment of patients with G/GEJ cancer is safe and well tolerated with encouraging durable PFS and survivals, especially for the patients with high/medium CLDN18.2 expression. Clinical trial information: NCT04495296 .