原研机构 |
非在研机构- |
权益机构- |
最高研发阶段临床2期 |
首次获批日期- |
最高研发阶段(中国)- |
特殊审评- |
开始日期2025-03-17 |
申办/合作机构 [+1] |
开始日期2024-03-28 |
开始日期2023-09-06 |
申办/合作机构 [+1] |
While CD40 agonism is an attractive approach for activating antigen-presenting cells and initiating antitumor responses, previous attempts have encountered limited clinical efficacy coupled with toxicity. We previously demonstrated that interactions between the antibody Fc domain and the inhibitory receptor FcγRIIB are critical for enhanced antitumor activity. Here, we present the results of a phase 1 study on intratumoral administration of an anti-CD40 agonistic antibody (2141-V11) Fc-engineered to enhance FcγRIIB binding. Primary endpoints included safety, maximum tolerated dose (MTD), and recommended phase 2 dose. Secondary objectives included preliminary clinical activity and correlative studies from biospecimens. 2141-V11 was well-tolerated without dose-limiting toxicities and MTD was not reached. In ten evaluable patients with metastatic cancer, the overall response rate was 20%, with complete responses in two patients (melanoma and breast carcinoma) and stable disease in six patients. 2141-V11 induced tumor regression in injected and non-injected lesions, with increased leukocyte infiltration and tertiary lymphoid structures (TLS) formation in post-treatment biopsies. In a humanized mouse model for CD40 and FcγRs, 2141-V11 induced TLS formation in mice bearing orthotopic breast carcinoma, correlating with local and abscopal antitumor effects, systemic immune activation, and immune memory. These findings support the safety and efficacy of 2141-V11, warranting phase 2 studies and suggesting a unique mechanism of action for this Fc-enhanced immunotherapy (NCT04059588).
适应症 | 最高研发状态 | 国家/地区 | 公司 | 日期 |
---|---|---|---|---|
前列腺癌 | 临床2期 | 美国 | 2024-03-28 | |
多形性胶质母细胞瘤 | 临床2期 | 美国 | 2023-09-06 | |
胶质母细胞瘤,IDH野生型 | 临床1期 | 美国 | 2025-03-17 | |
复发性胶质母细胞瘤 | 临床1期 | 美国 | 2025-03-17 | |
非肌层浸润性膀胱肿瘤 | 临床1期 | 美国 | 2021-11-08 | |
复发性恶性胶质瘤 | 临床1期 | 美国 | 2021-07-09 |
研究 | 分期 | 人群特征 | 评价人数 | 分组 | 结果 | 评价 | 发布日期 |
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临床1期 | 25 | 觸遞窪蓋餘憲獵襯衊襯(鬱顧窪鏇遞鑰糧窪淵鹽) = not reached 膚壓網鹹餘夢膚糧糧網 (繭鑰醖窪製願網選製獵 ) 更多 | 积极 | 2025-04-29 | |||
临床2期 | 复发性胶质母细胞瘤 IDH wild-type | 18 | D2C7-IT+2141-V11 via CED | 鹽願醖窪築夢鹹窪網憲(選鬱遞遞鹽顧製襯範淵) = grade 1 injection site reaction (n=16) 鹽窪鑰糧憲窪顧襯觸鏇 (範憲遞鏇醖膚窪選鹹襯 ) 更多 | 积极 | 2024-11-11 | |
临床1期 | 12 | 選簾鹹鬱憲積選鏇鏇選(顧鏇艱衊壓艱鏇願鹹衊) = 廠醖選繭鹽構壓醖積簾 選壓鬱憲構膚積醖夢蓋 (憲餘齋鹽鑰顧積繭衊願 ) 更多 | 积极 | 2024-11-05 | |||
临床1期 | - | 顧獵觸蓋積蓋膚鑰範膚(鏇鏇齋糧遞憲鏇鬱淵醖) = 膚糧淵齋鹹蓋獵獵鏇願 積膚蓋夢鏇淵齋遞壓範 (衊糧顧繭蓋網窪壓糧齋 ) 更多 | 积极 | 2024-06-03 | |||
临床1期 | 18 | 糧簾淵夢襯鏇鹽淵鬱襯(齋獵築繭簾膚積遞鑰鹽) = 襯製觸鏇餘積製範網製 衊醖衊鑰網獵壓艱範艱 (觸選築夢築鏇窪觸範築 ) | 积极 | 2024-05-01 | |||
临床1期 | 8 | 衊積遞觸膚鏇淵繭願窪(膚遞遞製蓋鏇鏇壓襯鹹) = 衊窪繭簾構簾衊餘齋襯 襯窪願簾壓淵憲憲製顧 (範餘鬱膚簾積築獵衊醖 ) | 积极 | 2022-06-02 |