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.
Jifang Gong, Dan Liu, Zengqing Guo, Jingdong Zhang, Weijian Guo, Meili Sun, Nong Xu, Chuan Qi, Lijuan Zhang, Zhenzhong Xia, Jianming Wang, Li Xu, Caroline Germa, Lin Shen
Abstract
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 .