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A phase 1b study of andecaliximab in combination with S-1 plus platinum in Japanese patients with gastric adenocarcinoma

Andecaliximab (ADX) is a monoclonal antibody that inhibits matrix metalloproteinase 9 (MMP9), an extracellular enzyme involved in matrix remodeling, tumor growth, and metastasis. In preclinical models, MMP9 inhibitors have been shown to enhance the cytotoxic effects of chemotherapeutic agents and to...

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Detalles Bibliográficos
Autores principales: Ooki, Akira, Satoh, Taroh, Muro, Kei, Takashima, Atsuo, Kadowaki, Shigenori, Sakai, Daisuke, Ichimura, Takashi, Mitani, Seiichiro, Kudo, Toshihiro, Chin, Keisho, Kitano, Shigehisa, Thai, Dung, Zavodovskaya, Marianna, Liu, JieJane, Boku, Narikazu, Yamaguchi, Kensei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9246925/
https://www.ncbi.nlm.nih.gov/pubmed/35773363
http://dx.doi.org/10.1038/s41598-022-13801-1
Descripción
Sumario:Andecaliximab (ADX) is a monoclonal antibody that inhibits matrix metalloproteinase 9 (MMP9), an extracellular enzyme involved in matrix remodeling, tumor growth, and metastasis. In preclinical models, MMP9 inhibitors have been shown to enhance the cytotoxic effects of chemotherapeutic agents and to suppress distant metastasis. In this phase Ib, multicenter study, the safety and efficacy of ADX combined with S-1 plus cisplatin (SP) or S-1 plus oxaliplatin (SOX) as a first-line treatment were evaluated in Japanese patients with advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma. ADX was administrated at a dose of 800 mg every 2 weeks for the SP cohort and 1200 mg every three weeks for the SOX cohort. As of December 2019, 16 patients were enrolled (six patients in the SP cohort and 10 patients in the SOX cohort). Peripheral sensory neuropathy (69%), anorexia (63%), nausea (56%), and decreased neutrophil counts (44%) were the most common adverse events (AEs). The grade 3 or higher AEs attributed to ADX were stomatitis and abnormal hepatic function (each one patient) in the SP cohort and decreased neutrophil counts (two patients) in the SOX cohort. The objective response rate in 11 patients with measurable target lesions was 73% (8/11), based on the investigator’s evaluation. Median progression-free survival was11.9 months (90% confidence interval, 5.6–16.6), and median overall survival was not reached. In conclusion, ADX combined with S-1 plus platinum demonstrated a manageable safety profile and promising clinical activity in the first-line treatment of patients with advanced gastric or GEJ adenocarcinoma. Clinical Trial Registration information: ClinicalTrials.gov Identifier: NCT02862535 (11/08/2016) and protocol ID: GS-US-296-1884.