Abstract 1524P
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 1st- 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.
Resources from the same session
1521P - Addition of durvalumab to CROSS in oesophageal adenocarcinoma is feasible and safe
Presenter: Hans Schloesser
Session: Poster session 21
1523P - Phase II dose optimization results from MOUNTAINEER-02: A study of tucatinib, trastuzumab, ramucirumab, and paclitaxel for HER2+ gastroesophageal cancer (GEC)
Presenter: Mustapha Tehfe
Session: Poster session 21
1526P - Phase Ib results of bemarituzumab (BEMA)+mfolfox6+nivolumab (NIVO) for advanced gastric/gastroesophageal junction cancer (G/GEJC): Fortitude-102 part 1
Presenter: Zev Wainberg
Session: Poster session 21
1527P - Efficacy and safety of infigratinib in locally advanced or metastatic gastric cancer or gastroesophageal junction adenocarcinoma patients with FGFR2 gene amplification
Presenter: Jiajia Yuan
Session: Poster session 21
1528P - A phase I/II trial investigating safety and efficacy of autologous TAC01-HER2 in relapsed or refractory solid tumors
Presenter: Daniel Olson
Session: Poster session 21
1529P - Tislelizumab plus chemotherapy sequential neo-chemoradiotherapy therapy as total neoadjuvant therapy in locally advanced esophageal squamous cell carcinoma (ETNT)
Presenter: Wenwu He
Session: Poster session 21
1530P - Health-related quality of life (hrqol) in patients with claudin-18 isoform 2-positive (CLDN18.2+) locally advanced (LA) unresectable or metastatic gastric or gastroesophageal junction (mg/GEJ) adenocarcinoma: Results from SPOTLIGHT and GLOW
Presenter: Florian Lordick
Session: Poster session 21
1532P - Phase Ib study of futibatinib plus pembrolizumab in patients with esophageal carcinoma: Updated results of antitumor activity and tolerability results in combination with chemotherapy
Presenter: Shun Yamamoto
Session: Poster session 21