1524P - First-line TST001 plus capecitabine and oxaliplatin (CAPOX) for advanced G/GEJ cancer with CLDN18.2 positive overall survival data from study transtar102-Cohort C

Background

Phase III studies (SPOTLIGHT and GLOW) showed that combining anti-Claudin18.2 (CLDN18.2) antibody with chemotherapy significantly improved outcomes for first-line treatment for G/GEJ cancer with high CLDN18.2 expression. TST001 is a potential best-in-class antibody with improved CLDN18.2 affinity and enhanced ADCC effect, leading to anti-tumor activity in low to medium CLDN18.2 expression gastric cancer animal models.

Methods

Cohort C from Transtar102 study was designed to explore the safety and efficacy of TST001 plus CAPOX as 1^st- line treatment in advanced G/GEJ cancer (NCT04495296–study Transtar102). Positive CLDN18.2 (membranous staining intensity ≥1+ in ≥10% of tumor cells) assessed centrally using the IHC 14G11 LDT assay was required in the expansion phase only.

Results

As of 21 April 2023, 64 patients have been dosed with TST001 plus CAPOX, including 15 patients who received TST001 at doses ranging from 1 to 8 mg/kg Q3W in the dose escalation phase and 49 patients at 6 mg/kg in the dose expansion phase. The median follow-up is 197.5 days. The most common treatment related adverse events are nausea (70.3%), vomiting (53.1%) and hypoalbuminemia (75%) with grade 3 being 1.6% each. 42 out of the 49 patients in the 6 mg/kg expansion cohort have measurable lesions and had at least one post-treatment tumor assessment, with 28 (66.7%) achieving partial response (confirmed and unconfirmed). Across all doses, the objective response rate (confirmed and unconfirmed) is 65.4%, the estimated median progression-free survival is 9.5 months, and the estimated median duration of response is 9.9 months. 38 of 49 patients are CLDN18.2 positive with no notable difference in efficacy per CLDN18.2 level. Overall survival is immature and will be updated at the time of the conference.

Conclusions

TST001 plus CAPOX as first-line treatment for patients with G/GEJ cancer demonstrated good safety and tolerability. Encouraging anti-tumor activities have been observed regardless of the CLDN18.2 expression levels, including expression as low as ≥10% tumor cells staining ≥1+, <40% tumor cells staining <2+ or 3+. Overall survival data will be presented.

Clinical trial identification

NCT04495296.

Editorial acknowledgement

Legal entity responsible for the study

Suzhou Transcenta Therapeutics Co, Ltd.

Funding

Suzhou Transcenta Therapeutics Co, Ltd.

Disclosure

All authors have declared no conflicts of interest.