Quizartinib Hydrochloride

– New Drug Application for ziftomenib in adults with R/R NPM1-m AML remains under FDA Priority Review, with a PDUFA target action date of November 30, 2025 – – KOMET 017 Phase 3 trials to evaluate ziftomenib in combination with intensive and non-intensive chemotherapy in frontline AML are accelerating; ziftomenib being investigated in settings representing more than 50% of AML patients – – Two oral presentations at 2025 ASH Annual Meeting on ziftomenib in combination with venetoclax / azacitidine chemotherapy in frontline and R/R NPM1-m AML – – Clinical data at ESMO 2025 Congress highlight promise of second strategic program – FTIs darlifarnib and tipifarnib show promising safety profile and clinical activity with targeted therapies in solid tumors – – $609.7 million in pro forma cash, together with anticipated collaboration payments, expected to support ziftomenib AML program through topline results in KOMET-017 – – Management to host webcast and conference call today at 8:00 a.m. ET – SAN DIEGO , Nov. 04, 2025 (GLOBE NEWSWIRE) -- Kura Oncology, Inc. (Nasdaq: KURA), a clinical-stage biopharmaceutical company committed to realizing the promise of precision medicines for the treatment of cancer, today reported third quarter 2025 financial results and provided a corporate update. “Our momentum is accelerating across the ziftomenib program and our broader precision oncology pipeline,” said Troy Wilson , Ph.D., J.D., President and Chief Executive Officer. “With the initiation of the pivotal KOMET-017 Phase 3 trials, we are executing a robust, focused development strategy to unlock ziftomenib’s best-in-class potential across the continuum of unmet need in AML. Bolstered by a strong balance sheet and our productive partnership with Kyowa Kirin, we are well positioned to advance ziftomenib toward commercialization, accelerate our frontline Phase 3 trials and create enduring value across our pipeline for patients and other key stakeholders.” Recent Highlights In September 2025 , we announced the first patient was dosed in the Phase 3 KOMET-017 trial of ziftomenib in frontline AML (NCT07007312). KOMET-017 comprises two global, randomized, double-blind, placebo-controlled trials to evaluate ziftomenib in combination with both intensive and non-intensive chemotherapy regimens in patients with newly diagnosed NPM1-m or KMT2A-rearranged (KMT2A-r) AML. In October 2025 , we announced the first patient was dosed in the FLT3 inhibitor cohort of the KOMET-007 clinical trial (NCT05735184). The cohort evaluates ziftomenib combined with the FDA-approved FLT3 inhibitor, quizartinib, plus cytarabine and daunorubicin (7+3) induction chemotherapy in patients with newly diagnosed AML harboring FLT3-ITD / NPM1 co-mutations. In September 2025 , the Journal of Clinical Oncolog y published the full results from the pivotal KOMET-001 clinical trial (NCT04067336) evaluating ziftomenib as a monotherapy in adult patients with R/R NPM1-m AML. (Reprint) Two abstracts featuring clinical data from ziftomenib in combination with venetoclax / azacitidine (ven/aza) chemotherapy in patients with newly diagnosed and R/R NPM1-m or KMT2A-r AML were accepted for oral presentation at the 67th Annual Meeting of the American Society of Hematology (ASH) to be held in December 2025 . (Abstract ID 764; Abstract ID 766) In October 2025 , preliminary clinical data were presented at ESMO 2025, highlighting the potential of Kura’s farnesyl transferase inhibitors, darlifarnib (KO-2806) and tipifarnib, to enhance the anti-tumor activity of PI3Ka inhibitors, KRAS inhibitors and antiangiogenic tyrosine kinase inhibitors across a range of diverse tumor types by addressing a common resistance pathway. Data from the FIT-001 Phase 1 trial evaluating darlifarnib and cabozantinib in patients with renal cell carcinoma (RCC) reflect a manageable safety profile across multiple dose levels of each agent, including at the full label dose of cabozantinib. Antitumor activity was observed across all dose combinations tested, including in patients with prior exposure to cabozantinib. The objective response rate (ORR) was 33-50% in ccRCC, and 17-50% in patients with prior cabozantinib exposure. (Poster) Data from the KURRENT-HN trial evaluating tipifarnib and alpelisib in patients with PIK3CA-dependent HNSCC also reflect a manageable safety profile. An ORR of 47% was observed at a dose of tipifarnib 1200 mg/day and alpelisib 250 mg/day. Robust antitumor activity was observed in a heavily pretreated patient population where clinical benefit is not expected from either alpelisib or tipifarnib as monotherapy. (Poster) In October and November 2025 , Kura received two $30 million milestone payments under its agreement with Kyowa Kirin in connection with first patient dosing in the pivotal KOMET-017 clinical trial of ziftomenib with intensive and non-intensive chemotherapy in patients with frontline AML. Data from the FIT-001 Phase 1 trial evaluating darlifarnib and cabozantinib in patients with renal cell carcinoma (RCC) reflect a manageable safety profile across multiple dose levels of each agent, including at the full label dose of cabozantinib. Antitumor activity was observed across all dose combinations tested, including in patients with prior exposure to cabozantinib. The objective response rate (ORR) was 33-50% in ccRCC, and 17-50% in patients with prior cabozantinib exposure. (Poster) Data from the KURRENT-HN trial evaluating tipifarnib and alpelisib in patients with PIK3CA-dependent HNSCC also reflect a manageable safety profile. An ORR of 47% was observed at a dose of tipifarnib 1200 mg/day and alpelisib 250 mg/day. Robust antitumor activity was observed in a heavily pretreated patient population where clinical benefit is not expected from either alpelisib or tipifarnib as monotherapy. (Poster) Forecasted Milestones Continued regulatory interactions with the FDA ahead of the November 30, 2025 PDUFA target action date for ziftomenib as a monotherapy for adult patients with relapsed or refractory NPM1-m AML. Present preliminary clinical data in newly diagnosed NPM1-m AML and updated clinical data in R/R NPM1-m and KMT2A-r AML from KOMET-007 cohorts evaluating ziftomenib in combination with ven/aza at ASH Annual Meeting to be held in December 2025 . Present preliminary data from the KOMET-008 cohort evaluating ziftomenib in combination with the FLT3 inhibitor gilteritinib in patients with R/R NPM1-m AML in 2026. Initiate FIT-001 Phase 1b expansion cohorts of darlifarnib and cabozantinib in patients with advanced RCC in the first half of 2026. Present updated dose-escalation data from the combination of darlifarnib and cabozantinib in patients with advanced RCC in 2026. Present preliminary clinical data from the combination of darlifarnib and adagrasib in patients with KRASG12C-mutated solid tumor indications in 2026. Financial Results Collaboration revenue from our Kyowa Kirin partnership for the third quarter of 2025 was $20.8 million , compared to no revenue for the third quarter of 2024. Research and development expenses for the third quarter of 2025 were $67.9 million , compared to $41.7 million for the third quarter of 2024. General and administrative expenses for the third quarter of 2025 were $32.8 million , compared to $18.2 million for the third quarter of 2024. Net loss for the third quarter of 2025 was $74.1 million , compared to a net loss of $54.4 million for the third quarter of 2024. Net loss for the third quarter included non-cash share-based compensation expense of $11.0 million , compared to $8.3 million for the same period in 2024. As adjusted for the two $30 million clinical trial milestone payments earned under our collaboration agreement with Kyowa Kirin, Kura had, on a pro forma basis, cash, cash equivalents and short-term investments of $609.7 million as of September 30, 2025 . Based on our current plans, we believe that our cash, cash equivalents and short-term investments as of September 30, 2025 will be sufficient to enable us to fund our current operating expenses into 2027, and, combined with anticipated funding under our collaboration agreement with Kyowa Kirin, should support our ziftomenib AML program through topline results from KOMET-017. Conference Call and Webcast - Third Quarter 2025 Financial Results Kura’s management will host a webcast and conference call at 8:00 a.m. ET / 5:00 a.m. PT today, November 4, 2025 , to discuss the financial results for the third quarter of 2025 and to provide a corporate update. A live webcast and archived replay of the event will be available here or online from the investor relations section of the Company’s website at www.kuraoncology.com. Conference Call and Webcast – ASH 2025 Annual Meeting Kura plans to host a virtual analyst and investor event at 12:30 p.m. ET / 9:30 a.m. PT on Monday, December 8, 2025 , to discuss the Company’s presentations from ziftomenib in combination with ven/aza chemotherapy in patients with newly diagnosed and R/R NPM1-m or KMT2A-r AML at the 67th Annual Meeting of the American Society of Hematology . A live webcast and archived replay of the event will be available online from the investor relations section of the Company’s website at www.kuraoncology.com. About Kura Oncology Kura Oncology is a clinical-stage biopharmaceutical company committed to realizing the promise of precision medicines for the treatment of cancer. The Company’s pipeline of small molecule drug candidates is designed to target cancer signaling pathways and address high-need hematologic malignancies and solid tumors. Kura is developing ziftomenib, a menin inhibitor targeting certain genetic drivers of acute myeloid leukemias, and it continues to pioneer advancements in menin inhibition for acute leukemias and solid tumors and in farnesyl transferase inhibition to address mechanisms of adaptive and innate resistance in the treatment of solid tumors. For additional information, please visit the Kura website at https://kuraoncology.com/ and follow us on X and LinkedIn. Forward-Looking Statements This news release contains certain forward-looking statements that involve risks and uncertainties that could cause actual results to be materially different from historical results or from any future results expressed or implied by such forward-looking statements. Such forward-looking statements include statements regarding, among other things, ziftomenib’s best-in-class potential across the continuum of unmet need in AML; Kura’s ability to advance ziftomenib toward commercialization, accelerate our frontline Phase 3 trials and create enduring value for patients and other stakeholders; the potential duration of FDA’s review of the NDA; the potential FDA approval of product candidates; the success and impact of interactions with the FDA; continued regulatory interactions with the FDA; the efficacy, safety and therapeutic potential of Kura’s product candidates, ziftomenib, darlifarnib and tipifarnib; the expected timing of clinical trials; the expected timing and presentation of results and data from clinical trials; the strength of Kura’s balance sheet and the sufficiency of cash, cash equivalents and short-term investments to fund Kura’s current operating expenses into 2027 and, combined with anticipated funding under our collaboration agreement with Kyowa Kirin, to support Kura’s ziftomenib AML program through topline results from KOMET-017. Factors that may cause actual results to differ materially include risks associated with the commercialization of ziftomenib, the risk that compounds that appeared promising in early research or clinical trials do not demonstrate safety and/or efficacy in later preclinical studies or clinical trials, uncertainties associated with performing clinical trials, regulatory filings, and other interactions with regulatory bodies, risks associated with reliance on third parties to successfully conduct clinical trials, the risks associated with reliance on outside financing to meet capital requirements, the risk that the collaboration with Kyowa Kirin is unsuccessful, and other risks associated with the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such drugs. You are urged to consider statements that include the words “may,” “will,” “would,” “could,” “should,” “believes,” “estimates,” “projects,” “promise,” “potential,” “expects,” “plans,” “anticipates,” “intends,” “continues,” “designed,” “goal,” or the negative of those words or other comparable words to be uncertain and forward-looking. For a further list and description of the risks and uncertainties the Company faces, please refer to the Company's periodic and other filings with the Securities and Exchange Commission, which are available at www.sec.gov. Such forward-looking statements are current only as of the date they are made, and Kura assumes no obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise. FLT3, Fms-like tyrosine kinase 3; HNSCC, head and neck squamous cell carcinoma; KMT2A, lysine methyltransferase 2A; NPM1, nucleophosmin 1; R/R, relapsed / refractory; ven/aza, venetoclax / azacitidine. Contacts Investors and media: Greg Mann 858-987-4046gmann@kuraoncology.com Source: Kura Oncology, Inc.

期刊：Cancer发表时间：2025.04.01 从“化疗时代”迈向“分子精准治疗时代” 在过去半个世纪中，急性髓系白血病（AML）一直是血液肿瘤中最复杂、最具挑战性的疾病之一。传统的“7+3”化疗方案虽奠定了治疗基础，但长期生存率一直徘徊不前。然而，过去十年，AML治疗领域发生了革命性转变：“靶向药物+个体化治疗+造血干细胞移植”构建了新的治疗范式。 2025年，美国德州大学MD Anderson癌症中心的Senapati等团队在《Cancer》杂志发表综述文章，系统总结了AML治疗的重大进展、现实挑战与未来方向。本文将带您深入解读这篇综述的核心内容。 从“单一疗法”到“个体化组合治疗”的转变 关键观点 AML的治疗改善并非一蹴而就，而是建立在数十年积累的“渐进式成功”之上。 作者指出，AML的基因组复杂性决定了单一疗法无效——组合疗法才是核心策略。 临床生存改善数据 <60岁患者的5年总生存率从15%提升至>50%； ≥60岁患者的3年总生存率从10%提升至35%； 移植相关非复发死亡率显著下降。 驱动因素 高通量基因组测序揭示了关键突变靶点（FLT3、IDH1/2、NPM1、KMT2A等）； 维奈托克（Venetoclax）联合低强度方案显著提升了老年患者疗效； 支持治疗与抗感染进步显著降低了诱导期死亡率； HSCT安全性提升，让更多老年患者获益。 分子分型驱动的精准治疗革命 FLT3突变AML：靶向抑制剂开启精准治疗先河 FLT3突变约占所有AML的25–30%。这一亚型过去预后极差，而FLT3抑制剂的出现彻底改变了局面。 米哚妥林（Midostaurin）（第一代FLT3抑制剂）首次确立了靶向治疗在AML诱导与巩固阶段的地位； 吉瑞替尼（Gilteritinib）与奎扎替尼（Quizartinib）（二代药物）显著改善复发/难治患者生存，QuANTUM-First研究显示中位OS从15个月提升至32个月； SORMAIN 试验证实，索拉非尼（Sorafenib）维持治疗可使 FLT3-ITD 患者移植后 2 年的 RFS 率从 53% 升至 85%，成为移植后标准方案。 当前MD Anderson推荐方案包括： 强度治疗人群采用CLIA+吉瑞替尼； 不能耐受者采用阿扎胞苷（Azacitidine）+维奈托克+FLT3抑制剂三联方案。 图1 MD安德森癌症中心在临床试验中或不进行临床试验的AML一线治疗方案 IDH1/2突变AML：分化治疗与维奈托克的协同 IDH突变占AML的10–20%，其代谢产物2-HG导致细胞分化阻滞。Ivosidenib（IDH1抑制剂）与Enasidenib（IDH2抑制剂）通过逆转分化障碍带来突破。 在VIALE-A试验中，维奈托克+HMA方案中IDH2突变患者CR率高达86%； AGILE研究显示阿扎胞苷+IDH1抑制剂b组的2年OS率达53%，远超对照组（17%）。 最新三联疗法（阿扎胞苷+维奈托克+IDH抑制剂）可达CR率>90%，MRD阴性率>80%，显示潜在治愈趋势。 ★机制亮点：IDH突变不仅是靶点，也提高了细胞对维奈托克的敏感性，是“天然联合”的理想靶系。 表1 伴有＞1个可靶向突变的AML患者选择合适靶向治疗的策略 TP53突变AML：仍是临床难题 TP53异常是AML中最具挑战性的亚型（约占25–30%），预后极差。尽管维奈托克方案能提高短期缓解率，但长期生存未显著改善；不过部分年轻、适合造血干细胞移植（HSCT）的患者，在达到深度缓解后仍可能获得长期生存”。 研究进展： Magrolimab（抗CD47抗体）与APR-246（p53再激活剂）在临床试验中未达预期； 正在开发针对特定TP53突变位点（如Y220C）的精准小分子； 新兴方向包括NK细胞疗法、抗体药物偶联物（如pivekimab sunirine）、CAR-T与BiTEs。 作者指出：“TP53突变AML的突破可能来自免疫与细胞治疗的融合创新。” KMT2A重排/NPM1突变AML：Menin抑制剂的里程碑 KMT2A重排与NPM1突变AML依赖HOX/MEIS1信号轴，Revumenib（Menin抑制剂）的出现成为该类AML的新希望。 Menin抑制剂于2024年获FDA批准用于治疗复发/难治KMT2A重排白血病； 临床数据显示其ORR为63%，CR率约23%； 口服方案地西他滨-西达尿苷（Decitabine–Cedazuridine）+维奈托克+Menin抑制剂）在Ⅰ/Ⅱ期试验中1年OS率达51%。 未来“维奈托克+Menin抑制剂”的组合或成为NPM1突变AML的一线治疗策略。 老年AML的曙光：低强度“维奈托克方案”成核心支柱 老年AML长期缺乏有效治疗手段，直至维奈托克的出现。 阿扎胞苷+维奈托克方案在VIALE-A研究中将中位OS从9.6个月提升至14.7个月，成为75岁以上患者的一线标准。 进一步优化方向包括： 缩短维奈托克暴露时长（避免骨髓抑制）； 三联方案（维奈托克+FLT3/IDH抑制剂）强化疗效； 全口服方案（地西他滨-西达尿苷+维奈托克）提升便利性。 ★临床数据亮点： 在MD Anderson的克拉屈滨（Cladribine）+LDAC+维奈托克试验中，中位OS达50个月，2年生存率>60%，显著优于传统化疗。 微小残留病灶（MRD）监测：精准决策的新基石 文章特别强调MRD在AML中的“第三次革命性意义”。 基于高灵敏度NGS与流式检测，MRD成为： 疗效动态评估指标； 决定是否进行HSCT的重要依据； 指导维持治疗强度与持续时间的关键工具。 NPM1和FLT3-ITD的MRD阴性状态被证实与最长生存期强相关。 未来展望：从“缓解”迈向“功能性治愈” 文章在结尾指出，AML治疗正朝三个方向迈进： 精准靶向的进一步深化：小分子、组合疗法、个体化剂量； 免疫疗法与细胞疗法的融合：CAR-T、BiTE、ADC、NK细胞等多维创新； 数据驱动的动态治疗：基于实时MRD与基因变化的治疗调整，实现“智能化白血病管理”。 “AML的未来不再是单一药物的胜利，而是分子医学、免疫工程与精准诊断的协奏曲。” 结  语 AML的治疗历程，是精准医学最具代表性的缩影之一。从靶点发现到药物开发，再到个体化方案设计，AML正在从“高复发率的绝症”逐步迈向“可长期控制甚至功能性治愈”的新时代。 未来十年，随着Menin抑制剂、免疫疗法与MRD监测体系的融合，AML的治疗格局有望被彻底改写。 原文链接：https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr.35806 获取原文：请回复"20251022" 大家都在看 RECOMMEND Lancet子刊专栏 | 人工智能重塑传染病防治：从预测、诊断到新药研发的全景解析 BMT | 儿童噬血细胞性淋巴组织细胞增多症（HLH）基因突变对造血干细胞移植结局的影响 Blood | 儿童ALL治疗关键突破：基于7640例CCCG多中心研究对天冬酰胺酶相关性胰腺炎风险与再使用策略的启示 撰写 | 赵倩倩       排版 | 肖蓉        排版 | 田沁汶