1419P - Osemitamab (TST001) plus nivolumab and CAPOX as the first-line therapy for the patients with advanced G/GEJ cancer (TranStar102)

Background

Osemitamab, a humanized monoclonal antibody with improved affinity to Claudin 18.2 (CLDN18.2) and enhanced antibody-dependent cell-mediated cytotoxicity, has exhibited synergistic effect with anti-PD-1 antibody and chemotherapy in pre-clinical studies. As checkpoint inhibitor plus chemotherapy is the current standard of care (SOC), we explored the combination of osemitamab with this SOC for the treatment of the CLDN18.2 positive 1L G/GEJ cancer patients.

Methods

Cohort G from TranStar102, a phase I/IIa study (NCT04495296), is designed to evaluate the safety and efficacy of osemitamab at doses of 3mg/kg or 6mg/kg Q3W plus nivolumab and CAPOX as the 1L treatment for patients with G/GEJ cancer. Advanced G/GEJ cancer patients with HER2 negative or unknown, regardless of CLDN18.2 or PD-L1 expression, were enrolled. CLDN18.2 and PD-L1 status were analyzed retrospectively using IHC 14G11 LDT assay and PD-L1 IHC 28-8 pharmDx at a central laboratory.

Results

As of April 18, 2024, 82 patients were dosed with osemitamab plus nivolumab and CAPOX (40 at 3mg/kg, 42 at 6mg/kg) with median follow-up 12.6 months. All patients experienced treatment-related adverse events (TRAE). The most common TRAE were hypoalbuminaemia, nausea and vomiting, most of them were of CTC AE grade 1 or 2 and manageable. Here we report the efficacy of patients with high/medium CLDN18.2 expression group in overall (n=32) and in subgroup with PD-L1 CPS less than 5 (n=22). The progression-free survival was 12.3 and 12.6 months, the objective response rate was 58.1% and 71.4%, respectively. The median duration of response (DoR) was not reached. Updated clinical data and details by biomarkers levels will be reported at the time of the conference.

Conclusions

Updated data indicate that the combination of TST001 plus nivolumab and CAPOX as the 1L treatment for patients with G/GEJ cancer is safe and well tolerated with very encouraging anti-tumor activities, especially for patients with high/medium CLDN18.2 expression when cross comparing to historical data.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Suzhou Transcenta Therapeutics Co., Ltd.

Funding

Suzhou Transcenta Therapeutics Co., Ltd.

Disclosure

L. Shen: Financial Interests, Personal, Advisory Board: MSD, BI, Servier, AZ, Transcenta Holding Limited; Financial Interests, Institutional, Funding: BeiGene, Ltd.; Financial Interests, Institutional, Trial Chair: Rongchang Pharmaceutical, Roche, Innovent, BeiGene, Ltd., NovaRock Biotherapeutics Limited. Z. Guo, J. Zhang, W. Guo, M. Sun, N. Xu: Financial Interests, Personal, Principal Investigator: Transcenta. C. Qi, X. Zhu, L. Zhang, L. Xu, C. Germa: Financial Interests, Personal, Full or part-time Employment: Transcenta; Financial Interests, Personal, Stocks/Shares: Transcenta.