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更新于：2026-02-07
SAR-439459
更新于：2026-02-07
概要
基本信息
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项与 SAR-439459 相关的临床试验NCT05231668
A Phase 1b, Single Ascending Dose, Randomized, Double-blind Study to Evaluate the Safety, Tolerability, and Activity of SAR439459 in Adults With Osteogenesis Imperfecta
NCT04729725
Strategic Alliance: Phase 1b Trial Assessing Combination of TGF-β Inhibitor and PD-1 Inhibitor Cemiplimab
NCT04643002
Phase 1-2 UMBRELLA Trial Evaluating Isatuximab With or Without Dexamethasone in Combination With Novel Agents Compared to Isatuximab With Pomalidomide and Dexamethasone in Relapsed or Refractory Multiple Myeloma (RRMM) - Master Protocol
100 项与 SAR-439459 相关的临床结果
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100 项与 SAR-439459 相关的转化医学
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100 项与 SAR-439459 相关的专利（医药）
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项与 SAR-439459 相关的文献（医药）2024-06-01CTS-Clinical and Translational Science
Safety, pharmacokinetics, pharmacodynamics, and antitumor activity of SAR439459, a TGFβ inhibitor, as monotherapy and in combination with cemiplimab in patients with advanced solid tumors: Findings from a phase 1/1b study
Article
作者: Abbadessa, Giovanni ; Demers, Brigitte ; Grob, Jean‐Jacques ; Wang, Rui ; Grob, Jean-Jacques ; Baranda, Joaquina C ; Barve, Minal ; Vieito, Maria ; Bechter, Oliver ; Robbrecht, Debbie ; Schadendorf, Dirk ; Johnson, Melissa ; Doger, Bernard ; Baranda, Joaquina C. ; Chen, Xiaofei ; Cantalloube, Cathy ; Santoro, Armando ; Hodi, F Stephen ; de Miguel, Maria Jose ; Lee, Jooyun ; Sullivan, Ryan ; Hodi, F. Stephen ; Pouzin, Clemence ; Amrate, Amele
Abstract:
SAR439459 (SAR'459), a “second‐generation” human anti‐transforming growth factor beta (TGFβ) monoclonal antibody, enhances the activity of immune checkpoint inhibitors. In this phase I/Ib study, we evaluated the safety, pharmacokinetics (PK), pharmacodynamics, and antitumor activity of SAR'459 ± cemiplimab (intravenous) in patients with advanced solid tumors. Increasing doses of SAR'459 were administered every 2 or 3 weeks (Q2W, Q3W) alone (Part 1A) or with 3 mg/kg cemiplimab Q2W or 350 mg Q3W (Part 1B). In Part 2A (dose expansion), melanoma patients were randomly (1:1) administered 22.5 or 7.5 mg/kg SAR'459. In Part 2B (dose expansion), 22.5 mg/kg SAR'459 and 350 mg cemiplimab Q3W were administered. The primary end points were maximum tolerated dose (MTD) or maximum administered dose (MAD; Part 1), preliminary antitumor activity (Part 2B), and optimal monotherapy dose (Part 2A). Twenty‐eight and 24 patients were treated in Parts 1A and 1B, respectively; MTD was not reached, MAD was 15 (Q2W) and 22.5 mg/kg (Q3W) alone and in combination, respectively. Fourteen and 95 patients, including 14 hepatocellular carcinoma (HCC) patients, were treated in Parts 2A and 2B, respectively. The population PK model yielded satisfactory goodness‐of‐fit plots and adequately described the observed data by a two‐compartment PK model with linear elimination. Objective responses were not observed in Parts 1 and 2A. In Part 2B, objective response rate was 8.4% and 7.1% across tumor types and the HCC cohort, respectively. The most frequent treatment‐emergent adverse effects were hemorrhagic events (43.5%), keratoacanthoma (6.8%), and skin neoplasms (6.2%). Fatal bleeding occurred in 21.4% HCC patients despite the implementation of mitigation measures. SAR'459 monotherapy and combination with cemiplimab appeared relatively safe and tolerable in limited number of patients in dose escalation. However, the study was discontinued due to the unclear efficacy of SAR'459 and bleeding risk, particularly in HCC patients.
2024-02-01Clinical and translational science
Biomarker and pharmacodynamic activity of the transforming growth factor‐beta (TGFβ) inhibitor SAR439459 as monotherapy and in combination with cemiplimab in a phase I clinical study in patients with advanced solid tumors
Article
作者: Elena Garralda ; Joon Sang Lee ; Oliver Bechter ; Elvire Pons‐Tostivint ; Dirk Schadendorf ; Giuseppe Curigliano ; Rui Wang ; Jean‐Jacques Grob ; Min‐Hee Ryu ; Hong Wang ; Patricia Martin Romano ; Massimo Di Nicola ; Marcus O. Butler ; Giovanni Abbadessa ; Bernard Doger ; Alejo Rodriguez‐Vida ; Ivan Borbath ; Brigitte Demers ; Robert Pomponio ; Amele Amrate ; Matteo Simonelli ; Tina Cheng ; Debbie Robbrecht
Abstract:
SAR439459, a ‘second‐generation’ human anti‐transforming growth factor‐beta (TGFβ) monoclonal antibody, inhibits all TGFβ isoforms and improves the antitumor activity of anti‐programmed cell death protein‐1 therapeutics. This study reports the pharmacodynamics (PD) and biomarker results from phase I/Ib first‐in‐human study of SAR439459 ± cemiplimab in patients with advanced solid tumors (NCT03192345). In dose‐escalation phase (Part 1), SAR439459 was administered intravenously at increasing doses either every 2 weeks (Q2W) or every 3 weeks (Q3W) with cemiplimab IV at 3 mg/kg Q2W or 350 mg Q3W, respectively, in patients with advanced solid tumors. In dose‐expansion phase (Part 2), patients with melanoma received SAR439459 IV Q3W at preliminary recommended phase II dose (pRP2D) of 22.5/7.5 mg/kg or at 22.5 mg/kg with cemiplimab 350 mg IV Q3W. Tumor biopsy and peripheral blood samples were collected for exploratory biomarker analyses to assess target engagement and PD, and results were correlated with patients' clinical parameters. SAR439459 ± cemiplimab showed decreased plasma and tissue TGFβ, downregulation of TGFβ‐pathway activation signature, modulation of peripheral natural killer (NK) and T cell expansion, proliferation, and increased secretion of CXCL10. Conversion of tumor tissue samples from ‘immune‐excluded’ to ‘immune‐infiltrated’ phenotype in a representative patient with melanoma SAR439459 22.5 mg/kg with cemiplimab was observed. In paired tumor and plasma, active and total TGFβ1 was more consistently elevated followed by TGFβ2, whereas TGFβ3 was only measurable (lower limit of quantitation ≥2.68 pg/mg) in tumors. SAR439459 ± cemiplimab showed expected peripheral PD effects and TGFβ alteration. However, further studies are needed to identify biomarkers of response.
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项与 SAR-439459 相关的新闻（医药）2024-07-29
2024-07-25
疫苗临床2期临床1期临床3期信使RNA
2023-11-01
100 项与 SAR-439459 相关的药物交易
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研发状态
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| 适应症 | 最高研发状态 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|---|
| 难治性多发性骨髓瘤 | 临床2期 | 美国 | 2021-01-25 | |
| 难治性多发性骨髓瘤 | 临床2期 | 澳大利亚 | 2021-01-25 | |
| 难治性多发性骨髓瘤 | 临床2期 | 法国 | 2021-01-25 | |
| 难治性多发性骨髓瘤 | 临床2期 | 德国 | 2021-01-25 | |
| 难治性多发性骨髓瘤 | 临床2期 | 希腊 | 2021-01-25 | |
| 难治性多发性骨髓瘤 | 临床2期 | 以色列 | 2021-01-25 | |
| 难治性多发性骨髓瘤 | 临床2期 | 意大利 | 2021-01-25 | |
| 难治性多发性骨髓瘤 | 临床2期 | 挪威 | 2021-01-25 | |
| 难治性多发性骨髓瘤 | 临床2期 | 葡萄牙 | 2021-01-25 | |
| 难治性多发性骨髓瘤 | 临床2期 | 韩国 | 2021-01-25 |
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临床结果
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临床1期 | 晚期恶性实体瘤 PD-1 | 3 | 齋淵願觸淵獵製繭積範(淵鹽壓糧蓋醖廠鹽廠艱) = Two grade 3 treatment-related adverse events were reported: rash 鹽淵獵選齋鏇築膚顧艱 (簾淵鬱淵窪鹹襯鏇顧鑰 ) 更多 | 不佳 | 2025-04-28 | ||
临床1期 | 109 | (Part 2A) | 壓觸醖鑰鏇築願糧鏇糧(鹹壓顧願蓋艱遞壓觸製) = 100% of pts had at least one treatment emergent adverse event (AE), 67% were G≥3, 34% related G≥3, 17% G5, and 4% related G5. 積廠鬱遞構艱遞憲衊鹽 (壓願憲糧鬱繭製壓鑰範 ) 更多 | 不佳 | 2022-06-02 | ||
(Part 2B) | |||||||
临床1期 | 晚期恶性实体瘤 mesenchymal CRC | CMS4 phenotype | - | 衊壓簾衊製鹽獵鏇簾餘(鬱鹹製壓淵廠鹽遞糧簾) = a trend of increased 糧壓淵醖窪糧遞壓夢築 (襯鏇齋窪壓選膚鏇衊鬱 ) 更多 | - | 2021-11-10 | ||
临床1期 | 52 | 鑰鏇夢願遞夢鹽蓋簾願(鑰鹽窪憲憲願鏇鏇齋鹽) = 鹹醖簾製獵衊構襯願網 選窪蓋鹽獵構窪膚醖顧 (選艱願蓋願範壓憲夢壓 ) 更多 | 积极 | 2021-05-20 | |||
鑰鏇夢願遞夢鹽蓋簾願(鑰鹽窪憲憲願鏇鏇齋鹽) = 壓鹽遞網衊遞繭築壓鹽 選窪蓋鹽獵構窪膚醖顧 (選艱願蓋願範壓憲夢壓 ) 更多 |
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