A Phase I/II Open-Label, Multi-centre Study to Assess the Safety and Tolerability of Roginolisib in Combination With Ruxolitinib in Patients With Myelofibrosis (MF) Who Are Unresponsive to JAK Inhibitors (HEMA-MED)

The goal of this clinical trial is to learn how roginolisib works in comparison to standard treatment in adult patients with Myelofibrosis. The main questions it aims to answer is to evaluate the safety and tolerability of roginolisib when administered in combination with ruxolitinib.

开始日期2025-11-17

申办/合作机构

iOnctura SA

CTIS2024-514954-63-00

/ Recruiting临床1/2期IIT

PLATFORM - A PLATFORM TRIAL, EVALUATING NEW DRUGS OR COMBINATION IN RELAPSED OR REFRACTORY PERIPHERAL T-CELL LYMPHOMAS

开始日期2025-08-20

申办/合作机构

Le LYSARC

100 项与 Roginolisib 相关的临床结果

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100 项与 Roginolisib 相关的转化医学

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100 项与 Roginolisib 相关的专利（医药）

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项与 Roginolisib 相关的文献（医药）

2024-07-22·Journal of Chemical Information and Modeling

Challenging Complexity with Simplicity: Rethinking the Role of Single-Step Models in Computer-Aided Synthesis Planning

Article

作者: Lai, Luhua ; Lin, Kangjie ; Pei, Jianfeng ; Li, Junren

Computer-assisted synthesis planning has become increasingly important in drug discovery. While deep-learning models have shown remarkable progress in achieving high accuracies for single-step retrosynthetic predictions, their performances in retrosynthetic route planning need to be checked. This study compares the intricate single-step models with a straightforward template enumeration approach for retrosynthetic route planning on a real-world drug molecule data set. Despite the superior single-step accuracy of advanced models, the template enumeration method with a heuristic-based retrosynthesis knowledge score was found to surpass them in efficiency in searching the reaction space, achieving a higher or comparable solve rate within the same time frame. This counterintuitive result underscores the importance of efficiency and retrosynthesis knowledge in retrosynthesis route planning and suggests that future research should incorporate a simple template enumeration as a benchmark. It also suggests that this simple yet effective strategy should be considered alongside more complex models to better cater to the practical needs of computer-assisted synthesis planning in drug discovery.

2024-05-01·Translational oncology

The highly selective and oral phosphoinositide 3-kinase delta (PI3K-δ) inhibitor roginolisib induces apoptosis in mesothelioma cells and increases immune effector cell composition

Article

作者: Falkenstern-Ge, Roger ; Conza, Giusy Di ; Lahn, Michael ; Kalla, Claudia ; Riganti, Chiara ; Niewola-Staszkowska, Karolina ; Finotello, Francesca ; Ott, German ; van der Veen, Lars ; Schüler, Julia ; Kopecka, Joanna

Targeting aberrantly expressed kinases in malignant pleural mesothelioma (MPM) is a promising therapeutic strategy. We here investigated the effect of the novel and highly selective Phosphoinositide 3-kinase delta (PI3K-δ) inhibitor roginolisib (IOA-244) on MPM cells and on the immune cells in MPM microenvironment. To this aim, we analyzed the expression of PI3K-δ by immunohistochemistry in specimens from primary MPM, cell viability and death in three different MPM cell lines treated with roginolisib alone and in combination with ipatasertib (AKT inhibitor) and sapanisertib (mTOR inhibitor). In a co-culture model of patient-derived MPM cells, autologous peripheral blood mononuclear cells and fibroblasts, the tumor cell viability and changes in immune cell composition were investigated after treatment of roginolisib with nivolumab and cisplatin. PI3K-δ was detected in 66/89 (74%) MPM tumors and was associated with reduced overall survival (12 vs. 25 months, P=0.0452). Roginolisib induced apoptosis in MPM cells and enhanced the anti-tumor efficacy of AKT and mTOR kinase inhibitors by suppressing PI3K-δ/AKT/mTOR and ERK1/2 signaling. Furthermore, the combination of roginolisib with chemotherapy and immunotherapy re-balanced the immune cell composition, increasing effector T-cells and reducing immune suppressive cells. Overall, roginolisib induces apoptosis in MPM cells and increases the antitumor immune cell effector function when combined with nivolumab and cisplatin. These results provide first insights on the potential of roginolisib as a therapeutic agent in patients with MPM and its potential in combination with established immunotherapy regimen.

2023-12-01·International journal of toxicology

Non-Clinical Toxicology Evaluation of the Novel Non-ATP Competitive Oral PI3 Kinase Delta Inhibitor Roginolisib

Article

作者: Deken, Marcel A. ; Lahn, Michael ; van der Veen, Lars ; Schmitt, Michael

Roginolisib (IOA-244) is a novel, non-ATP competitive phosphoinositide-3-kinase (PI3K) delta inhibitor that regulates Akt/mTOR signaling. Roginolisib was administered once daily to rats and dogs in dose-range finding (DRF) and 4-week GLP toxicology studies. Free plasma levels of roginolisib exceeded the cellular target engagement IC90 for PI3Kδ for ≥12 hours at doses of 5 mg/kg, the IC90 for PI3Kβ for ≥2 hours at doses ≥15 mg/kg, and the IC50 for PI3Kα for ≥2 hours at dose levels ≥45 mg/kg. Toxicity in rats occurred at doses ≥100 mg/kg. In dogs, we observed dose-dependent skin and gastrointestinal toxicity and doses ≥30 mg/kg had a greater incidence of mortality. Lymphoid tissue toxicity occurred in both species. Toxicities in dogs observed at the ≥15 mg/kg dose, affecting the digestive mucosa, liver, and skin, cleared after treatment cessation. Doses ≤75 mg/kg were tolerated in rats and the no-observed-adverse-effect-level (NOAEL) in rats was 15 mg/kg. Due to mainly epithelial lesions of the skin at 5 mg/kg and necrotizing damage of the intestinal epithelia at ≥15 mg/kg, no NOAEL was determined in dogs. However, the adverse effects observed in dogs at 5 mg/kg were considered monitorable and reversible in patients with advanced malignancies. Furthermore, the PK profile subsequently proved to be a decisive factor for achieving selective PI3Kδ inhibition without the toxicities observed in dogs. As the result of the unique PK profile of roginolisib, patients were able to take daily roginolisib without dose modification and showed pharmacodynamic PI3Kδ inhibition over several months without gastrointestinal or dermatologic toxicities.

项与 Roginolisib 相关的新闻（医药）

2025-12-04

·PRNewswire

iOnctura initiates Phase I/II trial in patients with myelofibrosis ahead of new non-clinical data at ASH

First patient dosed in Phase I/II HEMA-MED clinical trial (NCT06887803) evaluating the tolerability and efficacy profile of roginolisib (PI3Kδ inhibitor) plus ruxolitinib in myelofibrosis (MF) patients unresponsive to Janus kinase (JAK) inhibitors Dual-target approach: combining PI3Kδ and JAK inhibition addresses complementary disease mechanisms and may overcome unresponsiveness to JAK inhibitors in MF New supporting non-clinical data to be presented at the 67th American Society of Hematology (ASH) Annual Meeting in Orlando, Florida: Data from ex-vivo models of MF demonstrate roginolisib monotherapy activity and synergy with JAK inhibition GENEVA, AMSTERDAM and CAMBRIDGE, Mass., Dec. 4, 2025 /PRNewswire/ -- iOnctura, a clinical-stage biopharmaceutical company combating neglected and hard-to-treat cancers, today announces it has dosed the first patient in its Phase I/II clinical trial evaluating roginolisib in patients with MF who are no longer responding to JAK inhibition. Further details of the trial will be presented in a poster presentation at the 67th American Society of Hematology (ASH) Annual Meeting in Orlando, Florida on Sunday, December 7 at 6pm EST. This milestone marks an important step toward addressing the significant unmet medical needs of MF patients who face diminishing therapeutic options, as their disease progresses or becomes resistant to standard-of-care JAK inhibitor treatment. The Phase I/II trial is part of a comprehensive development program evaluating next-generation PI3Kδ inhibitor roginolisib's tolerability and anti-tumor response across a number of solid and hematologic malignancies. "Based on non-clinical data being presented at ASH, we anticipate that targeting both the PI3Kδ and JAK pathways could have a synergistic effect in MF — an approach that has previously eluded older generation PI3Kδ inhibitors because of their unfavorable tolerability profiles." said Dr Michael Lahn, Chief Medical Officer of iOnctura. Overactivation of the PI3K-Akt signaling pathway contributes to the occurrence and progression of cancer[1]. In MF, pathway activation is a well described mechanism of resistance in response to JAK inhibition[2]. Inhibition of this pathway using roginolisib may overcome the lack of response and lead to a beneficial therapeutic effect. Non-clinical evidence in support of this mechanism is being presented at ASH on Monday, December 8, 2025 at 6pm EST. These data demonstrate monotherapy activity of roginolisib against MF cell lines and in vitro models of primary MF cells. Further, roginolisib and JAK inhibition (ruxolitinib or momelotinib) exerts a synergistic anti-cancer effect. These data support the rationale behind the ongoing HEMA-MED clinical trial. Professor Alessandro Vannucchi, Professor of Hematology and Department Head of the Center for Research and Innovation in Myeloproliferative Neoplasms (CRIMM) at the University of Florence, Florence, Italy and Principal Investigator of the HEMA-MED study said: "Myelofibrosis patients often have suboptimal responses to ruxolitinib and/or acquire resistance over time. Roginolisib's intriguing mechanism of action and favorable toxicity profile position it as a compelling partner for ruxolitinib. By combining these agents, we could unlock more durable responses and redefine therapeutic expectations for this challenging rare disease." In addition to the two posters related to MF, trials in progress posters for the ongoing investigations of roginolisib in peripheral T-cell lymphoma and chronic lymphocytic leukemia (CLL) will also be presented at ASH. iOnctura poster presentations at the 67th ASH Annual Meeting in Orlando, Florida, USA: 1. A Vannucchi et al. Trial in progress: Sunday, December 7, 06:00 PM - 08:00 PM EST Abstract 25-4153: A study of roginolisib in combination with ruxolitinib in patients with myelofibrosis who are unresponsive to JAK inhibitors (HEMA-MED) 2. M Balliu et al.: Monday, December 8, 06:00 PM - 08:00 PM EST Abstract 25-7102: The selective PI3Kd inhibitor roginolisib synergizes with ruxolitinib against progenitor cells from naïve and JAK-inhibitor-refractory/resistant patients with myelofibrosis 3. D Sibon et al. Trial in progress: Sunday, December 7, 06:00 PM - 08:00 PM EST Abstract 25-11050: PlatΤform: A multicenter, multi-arm, academic platform trial evaluating novel agents and combinations in relapsed or refractory peripheral T-cell lymphomas 4. J Brown et al. Trial in progress: Sunday, December 7, 06:00 PM - 08:00 PM EST Abstract 25-7765: Roginolisib (IOA-244), an orally bioavailable, selective PI3Kδ inhibitor, in combination with venetoclax and rituximab in patients with relapsed chronic lymphocytic leukemia (CLL) About myelofibrosis (MF) MF is a rare myeloproliferative neoplasm marked by activation and growth of mutated cells in the bone marrow, with approximately 0.5 cases per 100,000 individuals diagnosed globally a year[3]. JAK inhibitors are a key treatment option for MF patients and improve symptoms and quality of life, but approximately half of patients discontinue therapy within three years[4]. Reasons for discontinuation include disease progression, tolerability and adverse events and death resulting from resistance to the JAK therapy[5],[6]. About the HEMA-MED clinical trial The HEMA-MED trial (NCT06887803) is a prospective, multi-center, open-label Phase I/II single arm trial consisting of two parts. Part 1 (Phase 1) will enroll 13 patients to assess the safety of the combination of the PI3Kδ inhibitor roginolisib in combination with the JAK inhibitor ruxolitinib, and Part 2 (Phase 2) will expand to enroll 13 additional patients to further allow the assessment of benefit/risk for all 26 patients. In addition to safety, the secondary endpoints of the HEMA-MED trial include blood biomarker and spleen reduction responses, and improvements of MF related symptoms. Exploratory measures will assess endpoints associated with the mechanism of action (MOA) of roginolisib. About iOnctura iOnctura is a clinical-stage precision oncology company combating neglected and hard-to-treat cancers with a pipeline of first-in-class small molecules. The bold new treatments extend lives and improve healthspans, changing the outlook for patients and their families. Lead asset, roginolisib, is a non-ATP competitive, allosteric modulator of PI3Kδ with a unique chemical structure and binding mode. Allosteric modulation is a new archetype for precise inhibition of PI3Kδ, promising clinical activity without the detrimental tolerability seen with previous generations of inhibitors. Roginolisib is being investigated in multiple randomized Phase II studies in solid and hematological malignancies. iOnctura is headquartered in Amsterdam, The Netherlands with subsidiaries located in Geneva, Switzerland and Cambridge, MA, USA. iOnctura is backed by specialist institutional investors including Syncona, M Ventures, Inkef Capital, EIC Fund, VI Partners, Schroders Capital and XGEN Venture. About roginolisib Roginolisib is a first-in-class, non-ATP competitive, allosteric modulator of PI3Kδ with a unique chemical structure and binding mode. Allosteric modulation is a new archetype for precise inhibition of PI3Kδ, promising clinical activity without the detrimental tolerability seen with previous generations of inhibitors. The PI3K signaling pathway is one of the most commonly dysregulated pathways across multiple cancer types. The potential of roginolisib has been validated by positive clinical signals in Phase I in solid tumor and hematological malignancies, including a doubling of overall survival compared to historical controls in rare eye cancer, uveal melanoma. The company has carefully designed its clinical program to allow full development in uveal melanoma, while in parallel validating the program in larger market indications. The Phase II OCULE-01 study in uveal melanoma started in March 2025, the PULMO-01 study in non-small cell lung cancer (NSCLC) started in May 2025 and the HEMA-MED Phase I/II study in myelofibrosis began in November 2025. For more information contact: Corporate Press Office: [email protected] [1] He et al., 2021 [2] Moyo et al., 2023 [3] Titmarsh et al., 2014 [4] Verstovsek et al., 2015 [5] Kuykendall et al., 2018 [6] Newberry et al., 2017 Logo - SOURCE iOnctura 21% more press release views with Request a Demo

临床2期ASH会议临床1期

2025-11-07

·N C S

通过变构调节克服耐药性策略

1. 变构调节的理论基础与机制1.1 变构调节的基本概念与作用原理变构调节指通过结合蛋白质非活性位点（变构位点），引发 “变构波” 或改变蛋白质振动模式，间接调节蛋白功能，实现对酶催化、基因表达等生物过程的精准调控，被称为 “生命的第二秘密”。1.2 与传统竞争性抑制的机制差异传统抑制剂直接竞争活性位点，易因靶点相似性产生副作用；变构调节剂通过构象变化间接作用，选择性更高（如氘可来昔替尼靶向 TYK2 调节结构域），剂量需求低、脱靶效应少，且通过改变蛋白质自由能景观发挥作用，机制更独特。1.3 克服耐药性的分子机制核心优势在于规避活性位点突变影响：变构位点进化压力低，突变概率小；调节剂可通过稳定非活性构象、改变构象动力学等多途径起效。例：BCR-ABL 变构抑制剂 ABL001 与正构药尼罗替尼联用，可重塑 BCR-ABL1 构象，增强药物亲和力，克服 T315M 突变耐药。1.4 近年理论研究进展技术方法：机器学习（如 DeepAllo、ALLOSE 模型）、AI 提升变构位点预测精度；分子动力学模拟结合 PocketMiner 工具助力变构口袋识别。机制突破：KRAS 研究中，量化 26,000 + 突变影响，发现中央 β 片层是变构传播关键区域，C 末端叶远端口袋具变构活性。2. 变构调节在不同药物类型中的应用2.1 抗癌药物中的变构调节策略2.1.1 靶向 EGFR 传统 ATP 竞争性抑制剂易耐药，变构抑制剂（如 EAI045）结合突变体特有的变构口袋（因 L858 等残基构象改变暴露），对 L858R、T790M 等突变体 IC50 达 3-49nM，可拓展至 EGFR^L861Q 突变。2.1.2 靶向 KRAS 索托拉西布（首个获批 KRAS G12C 变构抑制剂）结合开关 - II 口袋，锁定 KRAS 于失活态。KRAS 共 4 个活性口袋（开关 - I/II、C 末端叶远端口袋等），中央 β 片层介导变构传播，可调节效应子结合特异性。2.1.3 靶向 BCR-ABL 早期变构药 GNF-2/5 结合肉豆蔻酰口袋，与尼罗替尼联用可克服 T315I 突变；ABL001（阿西米尼）为首个 IV 型变构抑制剂，但肉豆蔻酰口袋突变（P465S、V468F 等）会导致耐药。2.1.4 其他靶点 IDH2：Enasidenib 结合二聚体界面，阻断 α-KG 向 2-HG 转化，但 Q316E/I319M 突变致耐药。 SHP2：nM 级变构抑制剂通过稳定自抑制构象抗食管癌；MEK 变构调节针对 RAS/RAF 突变相关肿瘤。2.2 抗生素中的变构调节策略2.2.1 靶向 PBP2a MRSA 的 PBP2a 活性位点闭合致 β- 内酰胺类耐药，头孢洛林结合 60Å 外变构位点，触发活性位点开放，允许第二个药物分子结合；临床突变体（如 E150K）破坏变构触发机制致耐药。2.2.2 其他细菌靶点 FtsZ：小分子结合 N/C 端裂隙，变构抑制细菌分裂； DNA 拓扑异构酶 / RNA 聚合酶：靶向变构位点影响催化活性或转录功能。2.2.3 抗生素耐药性的变构机制细菌通过改变关键蛋白变构网络（如 PBP2a 变构位点突变）适应抗生素压力，协调多通路变化实现耐药。2.3 抗病毒药物中的变构调节策略2.3.1 靶向病毒聚合酶 HCV NS5B 聚合酶含 5 个变构位点（拇指 I/II、手掌 I/II/III），VX-222 结合拇指 II 口袋，通过疏水作用抑制 RNA 合成。2.3.2 靶向病毒蛋白酶 HIV 整合酶变构药 Pirmitegravir 结合晶状体上皮衍生生长因子 /p75 位点，破坏病毒组装；HIV 蛋白酶抑制剂多依赖羟乙烯支架，替拉那韦为香豆素支架例外。2.3.3 其他病毒蛋白 HBV：CpAM 结合核心蛋白 HAP 口袋，异常组装核衣壳，抑制 pgRNA 包装；GST-HG141 形成空泡病毒颗粒。 SARS-CoV-2：靶向刺突蛋白 E-FIC 构象，设计双功能域药物（ACE2 蛋白 + EK1 多肽）。3. 临床试验进展追踪3.1 抗癌药物变构调节剂3.1.1 I 期 TGRX-678（BCR::ABL1 抑制剂）：入组 158 例 CML 患者，评估安全性与疗效； STX-478（PI3Kα 变构抑制剂）：在 HR+/HER2 - 乳腺癌等实体瘤中显抗肿瘤活性。3.1.2 II 期 Roginolisib（PI3Kδ 调节剂）：随机 II 期研究实体瘤与血液瘤疗效； RAP-219（AMPA 负变构调节剂）：减少耐药性局灶性发作患者长发作，达 IIa 期主要终点。3.1.3 III 期 Camzyos（心肌肌球蛋白变构抑制剂）：近 95% 患者达标，小分子上市申请在即。3.2 抗生素变构调节剂头孢洛林（抗 MRSA）已获批；FtsZ 抑制剂开发竞争性结合分析，辅助抗菌药研发。3.3 抗病毒药物变构调节剂 HBV：GLS4/RTV+ETV 联用，HBV pgRNA 等病毒学标志物降低更显著（-1.61 vs -0.28 log10 copies/ml）； HIV：Pirmitegravir 临床评估疗效与安全性。3.4 2024-2025 年最新结果帕金森病：GT-02287 获澳大利亚 Ib 期批准；精神疾病：NMRA-898（M4 PAM）启动 I 期；自身免疫病：A-005 完成 I 期，2025 下半年进 II 期（多发性硬化症）。4. 靶点蛋白和信号通路的分子机制分析4.1 肿瘤相关靶点4.1.1 EGFR 结构含胞外配体域、跨膜域、胞内激酶域；激活突变致短螺旋构象不稳定，暴露变构口袋；通过不对称二聚体激活，机制类似 cyclin-CDK 复合物。4.1.2 KRAS 小 G 蛋白，通过 GTP/GDP 结合切换活性态；开关 I/II 区构象变化影响效应子结合；4 个活性口袋介导变构调节，中央 β 片层变构传播具距离依赖性衰减。4.1.3 BCR-ABL 210-kDa 融合蛋白，肉豆蔻酰口袋（C 端叶）为关键变构位点；SH2 - 激酶域相互作用维持高催化活性，破坏该界面可抑制 CML 信号。4.1.4 其他靶点 IDH2：二聚体界面为变构位点； SHP2：双 SH2 结构域稳定自抑制构象。4.2 细菌相关靶点4.2.1 PBP2a 活性位点保护性环构象变化致耐药，变构位点通过多残基通路（E150、K153 等）传递信号至活性位点；E150K 突变破坏变构机制。4.2.2 其他细菌靶点 FtsZ：N 端 GTP 域与 C 端聚合域运动介导变构；拓扑异构酶：多域相互作用受变构调节。4.3 病毒相关靶点4.3.1 病毒聚合酶 NS5B 含手掌（催化）、拇指（RNA 结合）、手指（核苷酸结合）域，变构位点分布于各域，通过构象动力学调节活性。4.3.2 病毒蛋白酶及其他 HIV 整合酶：变构位点影响多聚化； HBV 核心蛋白：二聚体界面与 HAP 口袋介导变构组装。4.4 变构信号传导路径的分子基础 KRAS：中央 β 片层传播变构信号，链内衰减、片层间更高效； PBP2a：R297（变构位点）至 Y446（活性位点）多残基通路为关键；通用机制：局部构象变化、氢键重组、静电相互作用改变介导信号传递。5. 研究热点与发展趋势5.1 新的变构位点发现技术 AI 预测：蛋白质语言模型（ProtBERT-BFD）、多任务学习提升精度；注意力分数推断残基关系，无需额外训练。计算生物学：分子动力学 + 机器学习智能识别变构位点；MM/GBSA 计算预测结合亲和力。5.2 变构调节剂设计策略创新共价变构调节：结合共价高亲和力与变构高选择性，应用于 GPCR（A/B/C 类）。双位点结合：如 XL-3156/XL-3158 同时靶向正构与变构位点；cGAS 抑制剂靶向相分离 + 双位点。构象选择性调节：NET 内向开放构象 “瓣膜模型” 指导抗抑郁药开发；GPCR 变构调节剂（如 NTSR1）改变 G 蛋白亚型选择性。5.3 联合治疗方案的探索 BCR-ABL：ABL001 与伊马替尼联用克服突变耐药； KRAS：TEAD 抑制剂 GNE-7883 克服 KRAS G12C 抑制剂耐药；神经保护：mGlu2 抑制剂与东莨菪碱联用缓解抑郁样行为。5.4 技术挑战与转化壁垒变构位点识别：灵活性高、保守性低，预测难度大于正构位点；调节剂特异性：部分变构药仍存脱靶风险，需平衡亲和力与特异性；临床转化：安全性评估标准缺失、疗效生物标志物不足、药物相互作用复杂。5.5 2024-2025 年最新研究成果与专利技术：ProDomino 机器学习管道识别蛋白质结构域插入位点；专利：覆盖变构位点发现、调节剂设计、特定靶点新药；临床：GT-02287（帕金森）、NMRA-898（精神疾病）等推进临床。6. 结论与展望变构调节通过独特机制克服耐药性，在抗癌、抗生素、抗病毒领域均具临床价值（如索托拉西布、头孢洛林），AI 与计算生物学加速药物研发。未来需突破位点识别、特异性优化、临床转化壁垒，推动联合治疗、个性化医疗发展，拓展新靶点与机制，为药物研发提供新方向。

放射疗法

2025-10-14

·PRNewswire

iOnctura debuts cambritaxestat (IOA-28G) clinical data in patients with pancreatic cancer at ESMO

Cambritaxestat, the first autotaxin (ATX) inhibitor to be investigated in cancer patients, meets its primary endpoint in a study to assess safety and anti- tumour responses in patients with metastatic pancreatic cancer Combining cambritaxestat with gemcitabine/nab-paclitaxel (GnP) was tolerable and associated with anti-tumor responses Cambritaxestat administration combined with GnP demonstrated reduction in pharmacodynamic markers associated with fibrosis, immune regulation and tumor progression GENEVA and AMSTERDAM and CAMBRIDGE, Mass., Oct. 14, 2025 /PRNewswire/ -- iOnctura, a clinical-stage precision oncology company focused on neglected and hard-to-treat cancers, today announces the Phase Ib study investigating oral autotaxin (ATX) inhibitor, cambritaxestat (IOA-289), has met the primary endpoint: demonstrating safety, tolerability and anti-tumor responses, in combination with standard-of-care chemotherapy, in patients with previously untreated metastatic pancreatic ductal adenocarcinoma (mPDAC). These data are being presented as a poster at the European Society for Medical Oncology (ESMO) Congress in Berlin, Germany.1 Lead investigator, Davide Melisi, M.D., Ph.D, Associate Professor of Medical Oncology, and Director of the Digestive Molecular and Clinical Oncology Research Unit, University of Verona, and Investigational Cancer Therapeutics Clinical Unit at the University Hospital of Verona, Verona, Italy said, "These early findings with cambritaxestat are encouraging. Clinical activity alongside a manageable safety profile is particularly meaningful in a disease as aggressive and fibrotic as metastatic pancreatic cancer. These findings warrant continued scientific exploration in autotaxin inhibition." The Phase Ib dose escalation study, AION-02 (NCT05586516) evaluated cambritaxestat in combination with standard-of-care chemotherapy GnP in patients with previously untreated mPDAC. Sixteen patients received cambritaxestat orally, twice daily at doses of 100 mg (n=4), 200 mg (n=4), 400 mg (n=5) and 800 mg (n=3). GnP was administered by IV infusion, weekly for three weeks of a four-week cycle. The results show no dose-limiting toxicities, and no treatment-emergent adverse events (TEAE) leading to drug discontinuation or dose modification. Pharmacodynamic analysis showed a dose dependent reduction in the ATX-dependent plasma lipid LPA C18:2 over 24 hours supporting cambritaxestat's on-target effects. Patients in the higher-dose cohorts had consistent and durable reductions of the tumor marker CA19-9. These changes were associated with radiographic responses and survival. Dr. Michael Lahn, Chief Medical Officer at iOnctura said, "These data reinforce the therapeutic promise of targeting the autotaxin pathway to address the complex biology of pancreatic cancer, and potentially other tumors with high expression of autotaxin and its associated signaling. As we advance development, we remain focused on unlocking the potential of cambritaxestat to improve outcomes for patients facing some of the most challenging and hard-to-treat cancers." Cambritaxestat is the first autotaxin inhibitor to be investigated in cancer patients and is being developed as a first-in-class therapy across multiple cancer indications. This study was co-funded by the European Union and recruited patients in Italy and the United Kingdom. For more information contact: iOnctura Corporate Press Office: [email protected] About iOnctura iOnctura is a clinical-stage precision oncology company combating neglected and hard-to-treat cancers with a pipeline of first-in-class small molecules. The bold new treatments extend lives and improve healthspans, changing the outlook for patients and their families. Lead asset, roginolisib, is an allosteric modulator of PI3Kδ with a unique chemical structure and binding mode. Allosteric modulation is a new archetype for precise inhibition of PI3Kδ, promising clinical activity without the detrimental tolerability seen with previous generations of inhibitors. Roginolisib is being investigated in multiple randomized Phase II studies in solid and hematological malignancies. iOnctura is headquartered in Amsterdam, The Netherlands with subsidiaries located in Geneva, Switzerland and Cambridge, MA, USA. iOnctura is backed by specialist institutional investors including Syncona, M Ventures, Inkef Capital, EIC Fund, VI Partners, Schroders Capital and XGEN Venture. About cambritaxestat Cambritaxestat is an orally administered autotaxin inhibitor being developed for the treatment of highly fibrotic cancers, including metastatic pancreatic cancer. By targeting the autotaxin pathway, cambritaxestat offers a novel three-pronged approach—directly inhibiting tumor growth, stimulating immune effector cells, and reducing fibrosis to enhance drug and immune cell access to the tumor. Cambritaxestat received Orphan Drug Designation (ODD) from the U.S. Food and Drug Administration (FDA), in March 2024. This study was co-funded by the European Union. 1 ESMO Abstract #2227P: A Quinzii et al. Safety and clinical efficacy of cambritaxestat (IOA-289), a novel autotaxin inhibitor, plus gemcitabine and nab-paclitaxel (GnP) in patients with previously untreated metastatic pancreatic ductal adenocarcinoma (mPDAC). Abstract available, 13 October 2025. Poster presented at the European Society of Medical Oncology (ESMO) congress, 19 October 2025. Logo: SOURCE iOnctura WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

临床1期临床结果孤儿药ASCO会议临床2期

100 项与 Roginolisib 相关的药物交易

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适应症	最高研发状态	国家/地区	公司	日期
骨髓纤维化	临床2期	英国	iOnctura SA	2025-11-17
原发性血小板增多症后骨髓纤维化	临床2期	意大利	iOnctura SA	2025-11-17
原发性血小板增多症后骨髓纤维化	临床2期	西班牙	iOnctura SA	2025-11-17
真性红细胞增多症后骨髓纤维化	临床2期	意大利	iOnctura SA	2025-11-17
真性红细胞增多症后骨髓纤维化	临床2期	西班牙	iOnctura SA	2025-11-17
外周T细胞淋巴瘤	临床2期	法国	iOnctura SA	2025-08-20
晚期鳞状非小细胞肺癌	临床2期	比利时	iOnctura SA	2025-04-22
晚期鳞状非小细胞肺癌	临床2期	意大利	iOnctura SA	2025-04-22
晚期鳞状非小细胞肺癌	临床2期	西班牙	iOnctura SA	2025-04-22
转移性非小细胞肺癌	临床2期	比利时	iOnctura SA	2025-04-22

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT04328844 (DIONE-01, ESMO_IO2024) 人工标引	临床1期	葡萄膜黑色素瘤	29	Roginolisib	蓋淵艱網襯糧積鹹淵糧(壓壓衊壓鏇鏇醖繭憲顧) = 顧糧衊餘選鏇餘鑰艱獵窪願願鑰願餘遞襯範顧 (築製繭選壓網範網醖顧 ) 更多	积极	2024-12-12
NCT04328844 (Roginolisib (IOA-244), ESMO2024)	临床1期	葡萄膜黑色素瘤 CD63 expression on basophils \| blood-based proteins	29	Roginolisib 80 mg QD	網壓餘糧壓構鏇獵艱網(壓糧鏇膚憲糧襯顧顧壓) = 壓繭鹹製淵網網鹽淵鹽糧範淵夢遞糧壓廠簾膚 (鬱積顧製膚觸網艱鏇淵 )	积极	2024-09-14
NCT04328844 (FiH dose escalation study, ICML2023)	临床2期	滤泡性淋巴瘤	8	Roginolisib 80 mg QD	積壓鹽選淵齋構憲築顧(淵顧餘齋廠積網願鑰顧) = 願顧夢繭簾鹽願鏇築襯製積廠獵齋積醖遞顧顧 (鹹鏇鹽遞艱衊鑰廠壓顧 ) 更多	积极	2023-06-09
EHA2023	N/A	难治性滤泡性淋巴瘤	8	Roginolisib 20 mg QD	觸觸衊膚衊夢鏇廠糧顧(繭觸艱夢構鬱範製顧蓋) = AST/ALT elevation (G3) were observed in 2/8 pts 醖鹹繭蓋繭觸願積憲願 (鏇糧廠繭夢壓網鹽壓構 ) 更多	-	2023-06-08
				Roginolisib 80 mg QD
NCT04328844 (DIONE-01, ASCO 12023 \| ASCO 22023) 人工标引	临床1期	葡萄膜黑色素瘤 \| 晚期癌症	24	Roginolisib (Part A: pts with solid tumours and Follicular Lymphoma)	艱顧糧積網積鑰餘鏇膚(餘鹹獵遞顧製齋鑰艱遞) = roginolisib 80 mg QD 顧繭膚醖糧夢齋憲範簾 (顧鑰蓋遞鹹製餘艱範膚 ) 更多	积极	2023-05-26
				Roginolisib (Part A(dose escalation): UM pts)
NCT04328844 (ASCO2022) 人工标引	临床1期	晚期癌症	23	IOA-244 (Part A Solid Tumor (completed))	範築襯簾壓積艱醖選顧(顧選網範繭齋醖廠鹹醖) = 餘積糧餘艱遞窪觸鏇廠醖觸膚窪遞艱餘醖窪艱 (齋構壓壓糧構觸築蓋鹹 )	积极	2022-06-02
				IOA-244 (Uveal Melanoma Pts (progressed ≥1 line prior therapy))	襯襯襯鏇選觸鏇襯蓋蓋(鬱鏇範遞蓋齋製簾窪憲) = 積築範艱廠積獵餘衊鹽蓋糧鹹蓋醖網憲觸鏇獵 (夢範淵鏇簾築遞窪壓窪 ) 更多