1254P - Updated report of a phase I study of TST001, a humanized anti-CLDN18.2 monoclonal antibody, in combination with capecitabine and oxaliplatin (CAPOX) as a first-line treatment of advanced G/GEJ cancer

Background

TST001 is a humanized IgG1 antibody specifically against human Claudin 18.2 (CLDN18.2) with enhanced antibody-dependent cellular cytotoxicity. TST001 monotherapy dose-escalation study has been reported (IGCC2022-ABS-1152) and promising single agent anti-tumor activities were observed in CLDN18.2 + advanced gastric cancer patients. The current phase I clinical trial evaluates TST001 monotherapy or in combination with standard treatments in Chinese patients with advanced or metastatic solid tumors (NCT04495296).

Methods

This cohort is aimed to determine the recommended phase II dose, evaluate safety, tolerability and preliminary efficacy of TST001 in combination with CAPOX as the first-line treatment of advanced or metastatic G/GEJ cancer. A 3+3 design was utilized in the dose escalation phase in patients without CLDN18.2 preselection. CLDN18.2+ G/GEJ cancer patients were enrolled in the dose expansion phase.

Results

As of April 5, 2022, 12 patients had been dosed with TST001 with CAPOX at 1, 3, 6 and 8 mg/kg Q3W in the dose escalation and 14 patients in expansion phase. No subject experienced dose-limiting toxicity. The TST001 C_max and AUC increased as dose increased following the first infusion with effective T1/2 approximately 4 to 7 days. Treatment-emergent adverse events (TEAEs) were mostly grade 1-2, including nausea (84.6%), hypoalbuminemia (65.4%), anemia (61.5%), vomiting （53.8%), AST increased (42.3%). Treatment related grade 3 AEs were hypertension （11.5%）, nausea and vomiting, anemia, hypoproteinemia, WBC count decreased, hypocalcemia, ALT elevated, AST elevated (3.8%, respectively). Among the ten patients have measurable lesions from the dose-escalation phase without CLDN18.2 selection and with at least one post-treatment tumor assessment, five achieved partial response and four achieved stable disease as the best tumor response per RECIST1.1.

Conclusions

TST001 in combination with CAPOX in first-line G/GEJ cancer patients is safe and encouraging anti-tumor activities have been observed. Additional data from the dose expansion cohort will be updated at the meeting.

Clinical trial identification

NCT04495296.

Editorial acknowledgement

Legal entity responsible for the study

Suzhou Transcenta Therapeutics Co., Ltd.

Funding

Suzhou Transcenta Therapeutics Co., Ltd.

Disclosure

Z. Xia: Financial Interests, Personal, Member: Suzhou Transcenta Therapeutics Co., Ltd.. Y. shen: Financial Interests, Personal, Member: Suzhou Transcenta Therapeutics Co., Ltd.. J. Wang: Financial Interests, Personal, Member: Suzhou Transcenta Therapeutics Co., Ltd.. L. Lu: Financial Interests, Personal, Member: Suzhou Transcenta Therapeutics Co., Ltd.. C. Qi: Financial Interests, Institutional, Member: Suzhou Transcenta Therapeutics Co., Ltd.. J. Yao: Financial Interests, Personal, Member: Suzhou Transcenta Therapeutics Co., Ltd.. X. Qian: Financial Interests, Personal, Leadership Role: Suzhou Transcenta Therapeutics Co., Ltd.. M. Shi: Financial Interests, Personal, Leadership Role: Suzhou Transcenta Therapeutics Co., Ltd.. All other authors have declared no conflicts of interest.