预约演示
更新于：2025-12-20
Modakafusp Alfa
更新于：2025-12-20
概要
基本信息
药物类型 抗体融合蛋白 |
别名 Anti-CD38-targeted IGG4-attenuated IFNA TAK-573、TAK-573、TEV-48573 |
作用方式 抑制剂、激动剂 |
作用机制 CD38抑制剂(淋巴细胞分化抗原CD38抑制剂)、IFNAR激动剂(干扰素α/β受体复合体激动剂) |
在研适应症 |
非在研适应症 |
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)终止 |
特殊审评- |
登录后查看时间轴
结构/序列
Sequence Code 9995254L
来源: *****
Sequence Code 10134263H
来源: *****
关联
6
项与 Modakafusp Alfa 相关的临床试验CTR20223441
一项在复发难治多发性骨髓瘤患者中研究Modakafusp Alfa（TAK-573）单药治疗的安全性和耐受性、疗效、药代动力学和免疫原性的I/II期开放标签研究
NCT05590377
A Phase 1/2a Open-label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of Modakafusp Alfa in Combination With Daratumumab Subcutaneous in Patients With Relapsed or Refractory Multiple Myeloma
NCT05556616
A Phase 1b Open-label Study to Evaluate the Safety and Tolerability of Intravenous Modakafusp Alfa as Part of Combination Therapy in Adult Patients With Multiple Myeloma
100 项与 Modakafusp Alfa 相关的临床结果
登录后查看更多信息
100 项与 Modakafusp Alfa 相关的转化医学
登录后查看更多信息
100 项与 Modakafusp Alfa 相关的专利（医药）
登录后查看更多信息
4
项与 Modakafusp Alfa 相关的文献（医药）2025-08-28BLOOD
A phase 2 randomized study of modakafusp alfa as a single agent for patients with relapsed/refractory multiple myeloma
Article
作者: Nelson, Allison ; Beksac, Meral ; Vogl, Dan T. ; Holstein, Sarah A. ; Dimopoulos, Meletios A. ; Popat, Rakesh ; Suryanarayan, Kaveri ; Nadeem, Omar ; Travis, Patrick ; Touzeau, Cyrille ; Schjesvold, Fredrik ; Manier, Salomon ; Atrash, Shebli ; Mian, Hira ; Cherepanov, Dasha ; Frenzel, Laurent ; Gocke, Christian B. ; Gatt, Moshe E. ; Li, Shuli ; Magen, Hila ; Shah, Nishi ; Li, Cheryl ; Parot, Xavier
Abstract:
Modakafusp alfa is a first-in-class immunocytokine-directing interferon alfa to CD38+ cells. Our previous phase 1/2 trial identified 2 potential phase 2 doses of modakafusp alfa for patients with relapsed/refractory multiple myeloma (RRMM): 1.5 or 3 mg/kg every 4 weeks. The overall response rate (ORR) among 30 patients treated at 1.5 mg/kg was 43%. This phase 2 dose optimization study randomized 147 patients with triple-class refractory disease and ≥3 previous lines of therapy 1:1 to modakafusp alfa 120 mg (n = 71) or 240 mg (n = 75) every 4 weeks (fixed-dose equivalents of 1.5 and 3 mg/kg every 4 weeks). Patients had received a median of 6 previous lines of therapy; 66% were penta-exposed and 45% had previously been exposed to anti–B-cell maturation antigen (BCMA) therapy. Modakafusp alfa development was discontinued for strategic reasons by the sponsor and the study was terminated early. At median follow-up of 7.3 and 7.6 months in the 120- and 240-mg arms, ORRs were 32% and 41%, and median progression-free survival was 4.1 and 5.3 months, respectively. ORRs were higher in patients who had not received previous BCMA therapy (46% vs 29%). The most common treatment-related adverse events (TEAEs) in the 120- and 240-mg arms were thrombocytopenia (75% and 84%; grade ≥3, 55% and 61%; respectively) and neutropenia (68% and 73%; grade ≥3, 56% and 68%; respectively); 90% and 96% of patients, respectively, experienced grade ≥3 TEAEs; 39% and 44%, respectively, experienced serious TEAEs. Our results confirm the efficacy of single-agent modakafusp alfa for patients with RRMM. This trial was registered at www.clinicaltrials.gov as #NCT03215030.
2025-07-01CTS-Clinical and Translational Science
Population Pharmacokinetic and Pharmacokinetic‐Pharmacodynamic Modeling of Serum M‐Protein Response for Modakafusp Alfa in a Phase 1/2 Study of Patients With Relapsed or Refractory Multiple Myeloma
Article
作者: Parot, Xavier ; Li, Cheryl ; Yang, Lili ; Van Wart, Scott ; Cook, Sarah F. ; Gupta, Neeraj ; Mager, Donald E. ; Suryanarayan, Kaveri ; Santulli, Andrew
ABSTRACT:
Modakafusp alfa (TAK‐573) is a novel, first‐in‐class fusion protein of a humanized anti‐CD38 IgG4 kappa antibody fused to attenuated human interferon alfa‐2b. It acts as an agonistic innate immunity enhancer through targeted interferon (IFN) signaling and has been investigated as an immune‐oncology therapeutic agent in patients with relapsed/refractory multiple myeloma (RRMM). Population PK analysis and sequential PK‐PD analysis of serum M‐protein (MP) as a primary marker of tumor burden in RRMM were conducted using dose escalation (Part 1) and dose expansion (Part 2) data from 96 RRMM patients enrolled in the Phase 1/2 iinnovate‐1 trial. After exploring various structural PK models with different levels of mechanistic complexity, a Michaelis–Menten approximation model that included an anti‐drug antibody (ADA) binding model adequately captured the nonlinear PK of modakafusp alfa and the apparent time‐varying impact of ADA on the PK. Body weight was a significant predictor of central volume of distribution (exponent of 0.51) but was not predictive of elimination‐related parameters given both catabolic and likely target‐mediated elimination processes. Serum MP data from patients evaluable at baseline were adequately characterized using the Claret tumor growth inhibition and drug resistance model, with antitumor drug effect using an Emax model. The population PK and PK‐PD modeling results supported model‐informed drug development for modakafusp alfa, including the switch from weight‐based to fixed dosing and the selection of two fixed doses for the randomized dose extension (Part 3) phase of the trial to inform future optimal dose selection, which is consistent with the Project Optimus paradigm.
2025-02-27BLOOD
Targeted interferon therapy with modakafusp alfa for relapsed or refractory multiple myeloma
Article
作者: Kaufman, Jonathan L. ; Li, Cheryl ; Biran, Noa ; Vogl, Dan T. ; Holstein, Sarah A. ; Chaudry, Maria ; Suryanarayan, Kaveri ; Atrash, Shebli ; Collins, Sabrina ; Benson, Don ; Nadeem, Omar ; Liu, Yuyin ; Parot, Xavier
Abstract:
Interferon alfa has activity against multiple myeloma (MM). Modakafusp alfa is an immunocytokine comprising 2 attenuated interferon alfa-2b molecules and an anti-CD38 immunoglobulin G4 antibody, targeting delivery of interferon alfa to CD38-expressing (CD38+) immune and myeloma cells. This phase 1/2 trial enrolled patients with relapsed/refractory multiple myeloma with ≥3 prior lines of treatment and refractory to, or intolerant of, ≥1 proteasome inhibitor and ≥1 immunomodulatory drug. During dose escalation, modakafusp alfa was administered at 10 doses in 4 schedules across 13 cohorts. The primary end point was safety for dose escalation, and overall response rate (ORR) for dose expansion. We enrolled 106 patients who had received a median of 6.5 lines of prior therapy; 84% of patients had myeloma previously refractory to an anti-CD38 antibody. The most feasible dosing schedule was every 4 weeks (Q4W), at which the maximum tolerated dose was 3 mg/kg. Among 30 patients treated at 1.5 mg/kg Q4W, the ORR was 43.3%, with a median duration of response of 15.1 months (95% confidence interval [CI], 7.1-26.1); median progression-free survival was 5.7 months (95% CI, 1.2-14). Grade ≥3 adverse events (AEs) occurred in 28 (93.3%) patients, the most common were neutropenia (66.7%) and thrombocytopenia (46.7%); infections were reported in 8 (26.7%) patients (including grade 3 in 4 [16.7%]). Modakafusp alfa therapy induced upregulation of the type 1 interferon gene signature score, increased CD38 receptor density in CD38+ cells, and innate and adaptive immune cell activation. Modakafusp alfa resulted in antitumor activity and immune activation in patients with MM. AEs were primarily hematologic. This trial was registered at www.clinicaltrials.gov as #NCT03215030.
100 项与 Modakafusp Alfa 相关的药物交易
登录后查看更多信息
外链
| KEGG | Wiki | ATC | Drug Bank |
|---|---|---|---|
| - | - | - |
研发状态
10 条进展最快的记录, 后查看更多信息
登录
| 适应症 | 最高研发状态 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|---|
| 晚期恶性实体瘤 | 临床2期 | 美国 | 2019-12-12 | |
| 晚期恶性实体瘤 | 临床2期 | 澳大利亚 | 2019-12-12 | |
| BRAF V600E阳性黑色素瘤 | 临床2期 | 美国 | 2019-12-12 | |
| BRAF V600E阳性黑色素瘤 | 临床2期 | 澳大利亚 | 2019-12-12 | |
| 黑色素瘤 | 临床2期 | 美国 | 2019-12-12 | |
| 黑色素瘤 | 临床2期 | 澳大利亚 | 2019-12-12 | |
| 皮肤黑色素瘤 | 临床2期 | 美国 | 2019-12-12 | |
| 皮肤黑色素瘤 | 临床2期 | 澳大利亚 | 2019-12-12 | |
| 不可切除的黑色素瘤 | 临床2期 | 美国 | 2019-12-12 | |
| 不可切除的黑色素瘤 | 临床2期 | 澳大利亚 | 2019-12-12 |
登录后查看更多信息
临床结果
临床结果
适应症
分期
评价
查看全部结果
临床1/2期 | 15 | (Phase 1 (Dose Escalation) Modakafusp Alfa 80 mg + Daratumumab) | 鏇鬱範獵範夢獵願鏇簾 = 襯獵顧鏇鑰襯願淵觸築 觸醖窪窪糧簾窪憲選憲 (築衊鹹獵簾顧窪壓選膚, 鹽鑰夢顧餘鏇窪鹹襯簾 ~ 範製醖繭壓壓範鑰鹹製) 更多 | - | 2025-08-06 | ||
(Phase 1 (Dose Escalation) Modakafusp Alfa 120 mg + Daratumumab) | 鏇鬱範獵範夢獵願鏇簾 = 繭齋艱襯艱壓觸膚衊遞 觸醖窪窪糧簾窪憲選憲 (築衊鹹獵簾顧窪壓選膚, 積鑰壓艱簾齋鬱鑰艱積 ~ 壓廠鹽製觸襯艱簾鹹餘) 更多 | ||||||
临床1期 | 15 | (Group 1 (NDMM): Modakafusp Alfa 80 mg + Lenalidomide 10 mg) | 憲鑰襯蓋鏇鏇廠範憲鬱 = 願鹹衊艱淵鏇憲遞獵構 選鏇夢繭衊遞遞壓鏇夢 (觸鹽壓襯艱繭簾衊窪選, 艱網遞願鏇餘鹹壓觸簾 ~ 淵醖壓鬱網窪窪獵襯糧) 更多 | - | 2025-08-06 | ||
(Group 2 (RRMM Doublets): Modakafusp Alfa 80 mg + Pomalidomide 2 mg) | 憲鑰襯蓋鏇鏇廠範憲鬱 = 積顧艱蓋製鬱簾壓簾窪 選鏇夢繭衊遞遞壓鏇夢 (觸鹽壓襯艱繭簾衊窪選, 壓遞選鏇壓構簾淵構築 ~ 廠衊齋築壓獵構製顧憲) 更多 | ||||||
临床1期 | 100 | 艱醖鏇憲壓膚醖範淵蓋(願淵壓範艱窪鬱範遞憲) = 醖網鹽憲積憲淵衊膚蓋 鑰鹹遞淵積鑰鬱選構窪 (獵膚夢憲壓壓鹽網製糧, 1.2 ~ 15.9) 更多 | 积极 | 2022-11-15 | |||
選艱醖遞鏇鹽構鏇網獵(糧鬱網齋壓構選簾願齋) = 衊積膚窪窪餘醖壓鑰築 糧遞壓衊鬱繭壓糧夢鹹 (齋齋網鏇獵糧醖醖鏇壓 ) 更多 | |||||||
临床1/2期 | 30 | 簾鬱壓鏇憲觸願簾願襯(蓋廠願觸製餘鏇齋鏇齋) = 廠憲艱廠窪製簾鏇衊窪 構憲淵鹽積範蓋窪範壓 (蓋齋蓋衊積獵選鬱鏇淵 ) 更多 | 积极 | 2022-05-12 |
登录后查看更多信息
转化医学
使用我们的转化医学数据加速您的研究。
登录
或
药物交易
使用我们的药物交易数据加速您的研究。
登录
或
核心专利
使用我们的核心专利数据促进您的研究。
登录
或
临床分析
紧跟全球注册中心的最新临床试验。
登录
或
批准
利用最新的监管批准信息加速您的研究。
登录
或
生物类似药
生物类似药在不同国家/地区的竞争态势。请注意临床1/2期并入临床2期，临床2/3期并入临床3期
登录
或
特殊审评
只需点击几下即可了解关键药物信息。
登录
或
生物医药百科问答
全新生物医药AI Agent 覆盖科研全链路，让突破性发现快人一步
立即开始免费试用!
智慧芽新药情报库是智慧芽专为生命科学人士构建的基于AI的创新药情报平台，助您全方位提升您的研发与决策效率。
立即开始数据试用!
智慧芽新药库数据也通过智慧芽数据服务平台，以API或者数据包形式对外开放，助您更加充分利用智慧芽新药情报信息。
生物序列数据库
生物药研发创新
免费使用
化学结构数据库
小分子化药研发创新
免费使用