In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. 4062-4062
Abstract:
4062 Background: TST001 is a recombinant humanized IgG1 antibody specifically against human Claudin 18.2 (CLDN18.2) with high affinity and enhanced FcR engaging of NK cells, which can induce strong antibody-dependent cellular cytotoxicity (ADCC) activities. TST001 monotherapy dose-escalation study has been completed (IGCC2022-ABS-1152) and promising anti-tumor activities were observed in advanced gastric cancer patients with CLDN18.2 overexpression who had failed multiple lines of prior therapies. The current study is an open-label, multi-center, multiple cohorts, phase I clinical trial of 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 a 1 st line treatment of advanced G/GEJ cancer. A 3+3 design was utilized in the dose escalation phase with treatment naïve advanced G/GEJ cancer patients regardless of Claudin18.2 expression. Claudin 18.2 positive G/GEJ cancer patients were planned to be enrolled in the dose expansion phase in selected dose cohorts. Results: The TST001/CAPOX combination cohort was initiated in August 2021 and is ongoing in multiple sites in China with a data cutoff date of January 27, 2022. 12 subjects were dosed with TST001 with a dose range from 1 to 8mg/kg Q3W in combination with the standard dose of CAPOX in the dose escalation phase and one subject with central lab tested Claudin 18.2 overexpression was dosed in the expansion phase of TST001 at 6mg/kg Q3W with CAPOX. There was no subject experienced dose-limiting toxicity. Treatment-emergent adverse events (TEAEs) were mostly grade 1-2, including nausea (76.9%), anemia (69.2%), vomiting, AST increased (63.8% respectively), hypoalbuminemia, ALT increased (46.2%, respectively). Treatment related grade 3 AEs were hypertension (15.4%), anemia, hypoproteinemia, WBC count decreased, hypocalcemia aggravated (7.7%, respectively). Among the eight patients from the dose escalation part (with no CLDN18.2 expression selection yet with measurable disease ) with at least one post-treatment tumor assessment, four had achieved partial response, three had achieved stable disease and one had progressive disease as the best tumor response per RECIST1.1. Conclusions: Conclusion: TST001 in combination with CAPOX in first line gastric cancer patients is safe and encouraging anti-tumor activities have been observed. Additional data from the 6 mg/kg dose expansion cohort will be updated at the meeting. Clinical trial information: NCT04495296.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2022.40.16_suppl.4062
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2022
detail.hit.zdb_id:
2005181-5
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