Authors:

Lin Shen1, Dan Liu¹ , Ning Li², Weijian Guo², Tianshu Liu², Hongli Li², Jiayi Li², Fuyou Zhao², Meili Sun², Yuxian Bai², Yanhong Deng², Zhixiang Zhuang², Qingxia Fan², Liang Han², Simon Xia³, Xuelian Zhu³, Chuan Qi³, Li Xu³ , Xueming Qian³, Caroline Germa³;

1. Peking University Cancer Hospital. 

2. Investigators. 

3. Transcenta Therapeutics Inc.

Background:

• Adding CLDN18.2 antibody to chemotherapy is a clinically validated approach to improve longterm outcomes for patients with high CLDN18.2 expressing tumors (proved by GLOW and SPOTLIGHT).

• Osemitamab (TST001) is a potential best-in-class humanized antibody with high affinity for CLDN18.2 and enhanced ADCC (antibody-dependent cellular cytotoxicity), delivering potent antitumor activities in both low and high CLDN18.2 expressing tumors.

• Osemitamab monotherapy has stronger tumor growth inhibition effect than the zolbetuximab (IMAB362)-analog at the same dose, regardless of CLDN18.2 expression levels.

• Preclinical studies showed that TST001 plus chemotherapy had better inhibitory effects on tumor growth than chemotherapy.

Result:

• As of Apr. 21, 2023, a total of 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 195 days.

• 41 out of 49 patients in the dose expansion at 6mg/kg had CLDN18.2 positive tumor (see below for definitions, High: n=9, Medium: n=13, Low: n=19), 8 patients didn’t get their tumor tested (unknown CLDN18.2 expression). The baseline demographics of this dose expansion are similar to the overall population published on 2023 ASCO (abstract 4046*) and there are no clinically significant differences in baseline characteristics across different CLDN18.2 expression levels.

• The safety profile of osemitamab is mainly characterized by manageable on-target off-tumor effects and has been presented during 2023 ASCO (abstract 4046*). Most of these AEs are of grade 1 or 2 and occurring during the first 2 cycles.

• As of April 21, 2023, among the 49 patients at 6mg/kg from dose expansion, 42 patients had measurable lesions and at least one post treatment tumor assessment, 28 (66.7%) achieved partial response. Best overall response assessment by CLDN18.2 expressions levels at 6mg/kg in the dose expansion are presented in Table 1. The response rate appears similar regardless of the CLDN18.2 expression levels.

• As of the cut-off date, there is no clear trend between progression-free survival and the total (1+/2+/3+combined) CLDN18.2 expression levels (Figure 4). The same trend was observed whether CLDN18.2 expression was assessed by 2+/3+ combined or 3+ only (data not shown).

• As of cut-off date, 26 out of 64 patients had progression disease or death, with an estimated median progression-free survival (PFS) 9.5 months, median PFS stratified according to CLDN18.2 was immature and need long term follow-up (Figure 5).