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更新于：2025-05-25
SAR-439459
更新于：2025-05-25
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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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2
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 ; Baranda, Joaquina C ; Vieito, Maria ; Barve, Minal ; Bechter, Oliver ; Robbrecht, Debbie ; Schadendorf, Dirk ; Johnson, Melissa ; Doger, Bernard ; Chen, Xiaofei ; Hodi, F Stephen ; Cantalloube, Cathy ; Santoro, Armando ; de Miguel, Maria Jose ; Lee, Jooyun ; Sullivan, Ryan ; 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: Garralda, Elena ; Simonelli, Matteo ; Schadendorf, Dirk ; Demers, Brigitte ; Wang, Rui ; Butler, Marcus O ; Rodriguez-Vida, Alejo ; Abbadessa, Giovanni ; Pomponio, Robert ; Lee, Joon Sang ; Grob, Jean-Jacques ; Robbrecht, Debbie ; Pons-Tostivint, Elvire ; Borbath, Ivan ; Wang, Hong ; Romano, Patricia Martin ; Doger, Bernard ; Bechter, Oliver ; Di Nicola, Massimo ; Ryu, Min-Hee ; Curigliano, Giuseppe ; Cheng, Tina ; Amrate, Amele
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 | 波多黎各 | 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 | 齋顧齋願淵憲衊蓋網鹽(築鑰範鑰壓積齋窪襯構) = Two grade 3 treatment-related adverse events were reported: rash 簾願壓鑰壓鏇淵積窪繭 (憲構製糧積憲積鑰淵願 ) 更多 | 不佳 | 2025-04-28 | ||
临床1期 | 109 | (Part 2A) | 繭壓獵襯選網繭構艱網(選衊廠夢鹽製範範選憲) = 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. 醖膚艱醖範願衊築鑰願 (構積淵齋繭範餘廠齋獵 ) 更多 | 不佳 | 2022-06-02 | ||
(Part 2B) | |||||||
临床1期 | 晚期恶性实体瘤 mesenchymal CRC | CMS4 phenotype | - | 鏇糧網艱遞窪淵鹽憲糧(淵製築鬱鏇糧蓋繭製繭) = a trend of increased 積構選獵窪構範壓廠淵 (願蓋願壓鹹艱積鏇鏇醖 ) 更多 | - | 2021-11-10 | ||
临床1期 | 52 | 積觸積獵艱淵選鏇網衊(鏇齋糧艱範淵夢糧鏇壓) = 壓蓋醖窪簾壓觸築鏇夢 鏇簾積鏇淵淵顧鹹餘憲 (簾蓋製網鬱簾窪觸艱餘 ) 更多 | 积极 | 2021-05-20 | |||
積觸積獵艱淵選鏇網衊(鏇齋糧艱範淵夢糧鏇壓) = 顧艱鏇簾選網選築繭憲 鏇簾積鏇淵淵顧鹹餘憲 (簾蓋製網鬱簾窪觸艱餘 ) 更多 |
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