Phase Ib study of andecaliximab (GS-5745, ADX) in combination with S-1+platinum chemotherapy in Japanese subjects with advanced gastric or GEJ adenocarcinoma

• Published in: Journal of clinical oncology Vol. 37; no. 4_suppl; p. 53
• Main Authors: Muro, Kei, Satoh, Taroh, Yamaguchi, Kensei, Takashima, Atsuo, Kadowaki, Shigenori, Sakai, Daisuke, Ichimura, Takashi, Mitani, Seiichiro, Kudo, Toshihiro, Chin, Keisho, Kitano, Shigehisa, Bhargava, Pankaj, Zavodovskaya, Marianna, Liu, JieJane, Fukui, Masato, Boku, Narikazu
• Format: Journal Article
• Language: English
• Published: 01.02.2019
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2019.37.4_suppl.53

Abstract only 53 Background: 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, anti-MMP9 inhibited tumor growth, reduced metastases, and increased survival. In this study, safety, tolerability, PK, exploratory biomarkers, and preliminary efficacy of ADX in combination with anti-cancer agents were assessed. Methods: The safety and efficacy of ADX in combination with S-1+cisplatin (SP) or S-1+oxaliplatin (SOX) were evaluated in subjects with systemic chemotherapy naïve advanced gastric or GEJ adenocarcinoma. For SP cohort, six Japanese subjects received ADX 800 mg via IV infusion Q2W. For SOX cohort, 10 subjects received ADX 1200 mg IV Q3W. All subjects continued until PD or unacceptable toxicity. Results: As of August 2018, a total of 16 subjects received S-1+platinum with six subjects enrolled into the SP combination cohort and 10 subjects enrolled into the SOX combination cohort. ≥ Grade 3 AEs were mainly neutropenia (31%), amylase increased, CPK increased, hepatic function abnormal, anorexia, hyperglycaemia, hyponatraemia, anaemia, stomatitis, and peripheral sensory neuropathy (each 6%). The ORR in subjects with measurable target lesions was 73% (8/11) based on investigator evaluation. Median PFS and OS have not been reached. Exploratory biomarker analyses are ongoing. Conclusions: Preliminary safety data demonstrate a manageable safety profile for ADX in combination with S-1+platinum, and the combination appears to show promising response rates. Clinical trial information: NCT02862535.