更新于：2024-11-01

PD-1 x Fuc-GM1

更新于：2024-11-01

基本信息

关联

项与 PD-1 x Fuc-GM1 相关的药物

Atigotatug/Nivolumab

靶点

Fuc-GM1 x PD-1

作用机制

Fuc-GM1抑制剂 [+1]

在研机构

Bristol Myers Squibb Co.

原研机构

Bristol Myers Squibb Co.

在研适应症-

非在研适应症-

最高研发阶段临床3期

首次获批国家/地区-

首次获批日期1800-01-20

项与 PD-1 x Fuc-GM1 相关的临床试验

NCT06646276 / Not yet recruiting临床3期

A Randomized, Double Blind, Multicenter Phase 3 Trial of BMS-986489 (BMS-986012+Nivolumab Fixed Dose Combination) in Combination With Carboplatin Plus Etoposide vs Atezolizumab in Combination With Carboplatin Plus Etoposide as First-Line Therapy in Participants With Extensive-Stage Small Cell Lung Cancer (TIGOS).

The Purpose of the Study is to Compare the Efficacy and Safety of BMS-986489 (Anti-fucosyl-GM1+ Nivolumab Fixed Dose Combination) in Combination with Carboplatin plus Etoposide to that of Atezolizumab with Carboplatin plus Etoposide as First-Line Therapy in Participants with Extensive-Stage Small Cell Lung Cancer.

开始日期2025-01-21

申办/合作机构

Bristol Myers Squibb Co.

100 项与 PD-1 x Fuc-GM1 相关的临床结果

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100 项与 PD-1 x Fuc-GM1 相关的转化医学

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0 项与 PD-1 x Fuc-GM1 相关的专利（医药）

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项与 PD-1 x Fuc-GM1 相关的文献（医药）

2018-10-15·Clinical Cancer Research1区 · 医学

A Novel, Fully Human Anti–fucosyl-GM1 Antibody Demonstrates Potent In Vitro and In Vivo Antitumor Activity in Preclinical Models of Small Cell Lung Cancer

1区 · 医学

Article

作者: Wang, Xi-Tao ; Park, Kwon-Sik ; Chen, Bing ; Menezes, Daniel ; Rangan, Vangipuram S. ; Pan, Chin ; Sun, Huadong ; Oyasu, Miho ; Cardarelli, Pina M. ; Sage, Julien ; Cristea, Sandra ; LeBlanc, Heidi ; Ponath, Paul ; Deshpande, Shrikant ; Strachan, Debbie

AbstractPurpose: The ganglioside fucosyl-GM1 (FucGM1) is a tumor-associated antigen expressed in a large percentage of human small cell lung cancer (SCLC) tumors, but absent in most normal adult tissues, making it a promising target in immuno-oncology. This study was undertaken to evaluate the preclinical efficacy of BMS-986012, a novel, nonfucosylated, fully human IgG1 antibody that binds specifically to FucGM1.Experimental Design: The antitumor activity of BMS-986012 was evaluated in in vitro assays using SCLC cells and in mouse xenograft and syngeneic tumor models, with and without chemotherapeutic agents and checkpoint inhibitors.Results: BMS-986012 showed a high binding affinity for FcγRIIIa (CD16), which resulted in enhanced antibody-dependent cellular cytotoxicity (ADCC) against FucGM1-expressing tumor cell lines. BMS-986012–mediated tumor cell killing was also observed in complement-dependent cytotoxicity (CDC) and antibody-dependent cellular phagocytosis (ADCP) assays. In several mouse SCLC models, BMS-986012 demonstrated efficacy and was well tolerated. In the DMS79 xenograft model, tumor regression was achieved with BMS-986012 doses of 0.3 mg/kg and greater; antitumor activity was enhanced when BMS-986012 was combined with standard-of-care cisplatin or etoposide. In a syngeneic model, tumors derived from a genetically engineered model of SCLC were treated with BMS-986012 or anti-FucGM1 with a mouse IgG2a Fc and their responses evaluated; when BMS-986012 was combined with anti–PD-1 or anti-CD137 antibody, therapeutic responses significantly improved.Conclusions: Single-agent BMS-986012 demonstrated robust antitumor activity, with the addition of chemotherapeutic or immunomodulatory agents further inhibiting SCLC growth in the same models. These preclinical data supported evaluation of BMS-986012 in a phase I clinical trial of patients with relapsed, refractory SCLC. Clin Cancer Res; 24(20); 5178–89. ©2018 AACR.