A Phase 1/1b/2 Study of Cabozantinib in Combination with Selumetinib for Plexiform Neurofibroma in Adults and Adolescents with Neurofibromatosis Type 1

Based on the clinical activity of both selumetinib and cabozantinib as monotherapies in clinical trials, the demonstrated activity of these agents in reduced doses in preclinical studies, and the non-overlapping toxicity profiles, the study will assess the tolerability and efficacy of selumetinib and cabozantinib in combination in participants with NF1 ≥16 years old with progressive and/or symptomatic PN in a phase 1/1b/2 clinical trial.
Trial Design Phase 1 This will be an open label, dose escalation phase. Dose level escalation will be determined by a rolling six design. In this design, up to 6 participants can be enrolled at a given dose level and then evaluated for dose limiting toxicity (DLT) within the DLT window. The DLT window is defined as 16 weeks in this study based on the long half-life of cabozantinib and the desire to have maximum confidence about long-term tolerability of the combination prior to proceeding to the next dose level.
Phase 1b Once the recommended phase 2 dose has been determined in phase 1, an expanded cohort of 12 participants will be enrolled in phase 1b portion of the study.
Phase 2 This will be an open label, single-arm phase using the recommended phase 2 dose.

开始日期2025-01-01

申办/合作机构

The University of Alabama at Birmingham

[+2]

NCT05859217 / Not yet recruiting临床2期IIT

A Multi-center Phase II Study of Combining Cabozantinib and Atezolizumab as the 1st Line Therapy for PD-L1 Negative Advanced/Metastatic NSCLC (Cabatezo-1)

NSCLC patients with low expression level of PD-L1, esp. those with its level less than 1%, do not derive much benefit from anti-PD-1/L1 therapy (e.g. atezoilzumab). In this study, investigators hypothesize that the combination of cabozantinib (a multi-kinase inhibitor) and atezolizumab will result in better therapeutic value.

开始日期2024-12-01

申办/合作机构

University of Kansas

[+2]

NCT06341712 / Recruiting临床2期

A Phase II, Randomized, Open-label Study to Assess the Efficacy, Safety, and Pharmacokinetics (PK) of Maintenance Cabozantinib (XL184) Plus Best Supportive Care (BSC) Versus BSC in Children, Adolescents and Young Adults (AYA) With Unresectable Residual Osteosarcoma Either at Diagnosis or at First Relapse After Standard Treatment

The participants of this study will be children, adolescents, and young adults with residual osteosarcoma, which cannot be removed completely through surgery.
Participants will have achieved a partial response or stable disease at the end of conventional chemotherapy. Osteosarcoma is cancer of the bone. The cancer cells make immature bone cells, known as osteoid.
Osteosarcoma is very rare, but it is the most common type of bone cancer in children and teens. It is most common in teens and young adults.
In this study, participants will receive either cabozantinib and best supportive care or the best supportive care alone. Best supportive care will be provided at the investigator's discretion and according to institutional guidelines.
It includes antibiotics, nutritional support, correction of metabolic disorders, optimal symptom control and pain management (including radiotherapy), etc. but does not include tumor specific therapy.
Cabozantinib will be taken by mouth (orally), as a tablet, once a day. Cabozantinib will be provided to participants who tolerate it for as long as their disease does not progress. Participants in the study receiving best supportive care alone may switch to treatment with cabozantinib and best supportive care if their disease progresses and if other eligibility criteria are met.
Participants may withdraw consent to participate at any time.
The estimated duration of the study for participants is 24 months, however a participant could remain in the study longer if demonstrating treatment benefit.

开始日期2024-10-31

申办/合作机构

Ipsen SA

100 项与苹果酸卡博替尼相关的临床结果

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100 项与苹果酸卡博替尼相关的转化医学

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100 项与苹果酸卡博替尼相关的专利（医药）

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1,595

项与苹果酸卡博替尼相关的文献（医药）

2025-02-01·Current computer-aided drug design

Discovery of Novel Pyrimidine Based Small Molecule Inhibitors as VEGFR-2 Inhibitors: Design, Synthesis, and Anti-cancer Studies

Article

作者: Dabhade, Pratap S. ; Mokale, Santosh N. ; Dhawale, Sachin A.

Background::

Receptor tyrosine kinases (RTKs) are potent oncoproteins in cancer that, when mutated or overexpressed, can cause uncontrolled growth of cells, angiogenesis, and metastasis, making them significant targets for cancer treatment. Vascular endothelial growth factor receptor 2 (VEGFR2), is a tyrosine kinase receptor that is produced in endothelial cells and is the most crucial regulator of angiogenic factors involved in tumor angiogenesis. So, a series of new substituted N-(4-((2-aminopyrimidin-5-yl)oxy)phenyl)-N-phenyl cyclopropane1,1-dicarboxamide derivatives as VEGFR-2 inhibitors have been designed and synthesized.

Methods::

Utilizing H-NMR, C13-NMR, and mass spectroscopy, the proposed derivatives were produced and assessed. HT-29 and COLO-205 cell lines were used for the cytotoxicity tests. The effective compound was investigated further for the Vegfr-2 kinase inhibition assay, cell cycle arrest, and apoptosis. A molecular docking examination was also carried out with the Maestro-12.5v of Schrodinger.

Results::

In comparison to the reference drug Cabozantinib (IC50 = 9.10 and 10.66 μM), compound SP2 revealed promising cytotoxic activity (IC50 = 4.07 and 4.98 μM) against HT-29 and COLO-205, respectively. The synthesized compound SP2 showed VEGFR-2 kinase inhibition activity with (IC50 = 6.82 μM) against the reference drug, Cabozantinib (IC50 = 0.045 μM). Moreover, compound SP2 strongly induced apoptosis by arresting the cell cycle in the G1 phase. The new compounds' potent VEGFR-2 inhibitory effect was noted with key amino acids Asp1044, and Glu883, and the hydrophobic interaction was also observed in the pocket of the VEGFR-2 active site by using a docking study.

Conclusion::

The results demonstrate that at the cellular and enzyme levels, the synthetic compounds SP2 are similarly effective as cabozantinib. The cell cycle and apoptosis data demonstrate the effectiveness of the suggested compounds. Based on the findings of docking studies, cytotoxic effects, in vitro VEGFR-2 inhibition, apoptosis, and cell cycle arrest, this research has given us identical or more effective VEGFR-2 inhibitors.

2024-12-01·JOURNAL OF CONTROLLED RELEASE

Cabozantinib-encapsulated and maytansine-conjugated high-density lipoprotein for immunotherapy in colorectal cancer

Article

作者: Jiang, Chen ; Zhang, Yuan ; Zhao, Mengmeng ; Pu, Rong ; Wang, Hao ; Zhang, Wen ; Jiang, Linyang ; Li, Yaping ; Zhang, Pengcheng ; Gong, Xiang ; Zheng, Chao

Advanced colorectal cancer (CRC) responds poorly to current adjuvant therapies, partially due to its immunosuppressive intestinal microenvironment. We found that myeloid-derived suppressor cells (MDSCs) were enriched in orthotopic tumors due to treatment-induced succinate release, which activated tuft cells and upregulated interleukin 25 (IL-25) and interleukin 13 (IL-13). We engineered a cabozantinib (Cabo)-encapsulated and maytansine (DM1)-conjugated synthetic high-density lipoprotein (^EC^CD-sHDL) to modulate the tumor microenvironment. DM1 induced immunogenic cell death and promoted the maturation of dendritic cells. Meanwhile, Cabo alleviated DM1-induced succinate release, preventing tuft cell activation, downregulating IL-25 and IL-13 secretion, and reducing intratumoral MDSC infiltration. ^EC^CD-sHDL increased the densities of active cytotoxic T lymphocytes (CTLs) and M1 macrophages in the tumors, effectively inhibiting tumor growth and metastasis, thereby prolonging survival in murine CRC models. Our study sheds light on the mechanism of treatment-induced immunosuppression in orthotopic CRC and demonstrates that this combinatorial therapy could be an effective treatment for CRC.

2024-12-01·CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY

Sequencing of systemic therapy in unresectable hepatocellular carcinoma: A systematic review and Bayesian network meta-analysis of randomized clinical trials

Review

作者: Cao, Shasha ; Li, Jianjun ; Wang, Haochen ; Zhang, Yonghong ; Wang, Qi ; Yu, Jianan ; Hu, Caixia ; Sun, Xuedong ; Li, Jian ; Yang, Zeran ; Han, Yanjing ; Jin, Long

PURPOSE:

For patients with advanced or unresectable hepatocellular carcinoma (HCC), safe and effective therapies are urgently needed to improve their long-term prognosis. Although the guidelines recommend first-line treatments such as sorafenib, lenvatinib, and atezolizumab in combination with bevacizumab (T+A) and second-line treatments such as regorafenib, the efficacy comparison between drugs is lacking, that is, a treatment is not recommended as the optimal or alternative choice for a specific patient population. Therefore, we will conduct a high-quality network meta-analysis based on Phase III randomized controlled trials (RCTs) to systematically evaluate and compare overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and serious adverse events (SAE) of different treatment protocols in the context of first-line and second-line therapies, which are critical for clinical decision making and prognostic improvement in advanced HCC patients.

METHODS:

The studies of interest were Phase III RCTs evaluating the efficacy or safety of first- or second-line therapies in patients with unresectable or advanced HCC. Literature published in English from the four databases of PubMed, Embase, Cochrane Library, and Web of Science was comprehensively searched from the inception to May 23, 2022. Outcomes of interest included OS, PFS, ORR, and SAE. A league table was developed to show the results of the comparison between different treatments. A histogram of cumulative probability was drawn to discuss the ranking probability of treatments based on different outcomes. The effectiveness and safety of various treatments were comprehensively considered and the two-dimensional diagram was plotted to guide clinical practice. The Gemtc package in R Studio was used for network meta-analysis in a Bayesian framework.

RESULTS:

The results showed that HAIC-FO was superior to T+A regimen, regardless of OS, PFS or ORR. TACE combined with lenvatinib performed better than T+A in PFS, and ORR. In addition to the T+A regimen, Sintilimab combined with IBI305 and camrelizumab combined with apatinib were also associated with longer OS, PFS, and ORR, and their SAE incidence was not higher than that of T+A, especially for camrelizumab combined with apatinib, its safety was better than that of T+A regimen. There were no new treatments or combinations that were more effective than regorafenib. It was important to note that for PFS, the efficacy of apatinib and cabozantinib was not statistically different from that of regorafenib, so these two treatments could be used as alternative treatment options in cases where regorafenib was not tolerated or treatment failed.

CONCLUSIONS:

We conducted a network meta-analysis to evaluate the efficacy and safety of multiple treatment modalities by integrating the results of direct and indirect comparisons. This study included high-quality multicenter Phase III RCTs, collated and summarized all treatments involved in advanced or unresectable HCC in first-line and second-line settings, and compared with T+A and regorafenib, respectively, and ranked based on efficacy and safety to support clinical decision making.

477

项与苹果酸卡博替尼相关的新闻（医药）

2024-11-14

·ioncology

国际视角丨肝癌一线免疫治疗进展后何去何从？

点击蓝字关注我们编者按免疫治疗已改变了不可切除肝细胞癌（HCC）的治疗格局。目前，阿替利珠单抗联合贝伐珠单抗（atezo-bev）和度伐利尤单抗联合tremelimumab在许多国家已获得监管部门的批准，作为HCC患者的一线治疗选择。此外，也有数据支持其他免疫治疗组合的使用，如纳武利尤单抗联合伊匹木单抗（nivo-ipi）、卡瑞利珠单抗联合瑞戈非尼和信迪利单抗联合贝伐珠单抗生物类似药。但是，对于在一线免疫治疗后疾病仍出现进展的HCC患者而言，如何确定最佳后续治疗方案成为了一个治疗难题和亟待满足的临床需求。当前国际指南普遍倾向于推荐在免疫治疗后采多激酶抑制剂（MKI）药物（诸如索拉非尼或仑伐替尼），这一建议主要基于以下几点考量：这些药物在一线治疗中的疗效与安全性已得到证实；这些药物具有广泛的可用性；同时，其作用机制也被认为是合理的。然而，需要注意的是，在此特定情境下，这些推荐尚缺乏直接基于确凿证据的支持。因此，香港中文大学威尔斯亲王医院临床肿瘤科的Landon L.Chan博士、加州大学旧金山分校Helen Diller家庭综合癌症中心的Robin K Kelley博士、香港中文大学香港癌症研究所邵逸夫爵士癌症中心转化肿瘤学国家重点实验室的Stephen L. Chan博士回顾了近日发布的前瞻性和回顾性研究数据，总结出了一套在晚期HCC患者一线免疫治疗后出现疾病进展后的治疗方法。从左到右依次为：Dr. Landon L.Chan、Dr. Robin Katie Kelley、Stephen L. Chan 一、免疫治疗进展后应用MKI的前瞻性研究数据 1.卡博替尼最近一项在亚洲进行的多中心Ⅱ期研究证明了卡博替尼在免疫治疗失败后患者中的疗效和安全性，这是该领域的第一项前瞻性证据。该研究纳入了47例接受过1种或多种前期免疫治疗的患者。总体中位无进展生存期（mPFS）为4.1个月，中位总生存期（mOS）为9.9个月。当仅限于二线治疗环境时，卡博替尼的mPFS为4.3个月，mOS为14.3个月。值得注意的是，这些数值与索拉非尼和仑伐替尼在二线环境中的真实世界疗效相当，mPFS在3~6个月之间，mOS在12~18个月之间。安全性特征与以往研究相似，最常见的不良反应包括手足皮肤反应、疲劳和腹泻。尽管如此，3级或更高级别的毒性反应并不常见，最常见的3级或更高级别的毒性反应是血小板减少症。 2.瑞戈非尼在2024年美国临床肿瘤学会胃肠道肿瘤研讨会（ASCO GI）上，另一种MKI药物瑞戈非尼被评估作为一线阿替利珠单抗联合贝伐珠单抗治疗后疾病进展的不可切除HCC患者的二线治疗方案。该研究是在韩国进行的一项前瞻性Ⅱ期临床研究，共入组40例患者，所有患者先前均接受过至少2个周期的阿替利珠单抗联合贝伐珠单抗治疗。在疗效方面，患者的mPFS为3.5个月，mOS为9.7个月，ORR为10%，疾病控制率（DCR）为82.5%。在安全性方面，高级别治疗相关不良事件（TRAEs）不常见，最常见的3~4级TRAEs包括血小板减少症（5.0%）、手足皮肤反应（2.5%）和疲劳（2.5%）。 3.瑞戈非尼联合帕博利珠单抗在2024年ASCO年会上，瑞戈非尼联合帕博利珠单抗被评估为另一种治疗一线免疫治疗失败后疾病进展的晚期HCC患者的治疗选择。在这项国际Ⅱ期研究中，共入组了95例患者，其中先前接受过阿替利珠单抗联合贝伐珠单抗治疗的患者组成队列1（68例），先前接受过其他免疫治疗的患者组成队列2（27例）。在68例先前接受阿特珠单抗联合贝伐珠单抗治疗后疾病进展并接受瑞戈非尼联合帕博利珠单抗联合治疗的患者中，mPFS为2.8个月，ORR为5.9%。在其余27例一线接受其他免疫治疗的患者中，mPFS为4.2个月，ORR为11.1%。由于随访时间相对较短（中位7.1个月），两个队列均未达到mOS。两队列中分别有37%和3%的患者观察到3级或4级药物相关治疗期不良事件，1例患者因治疗发生5级事件（心脏骤停）。对治疗无应答患者的相关性生物标志物分析显示，瑞戈非尼联合帕博利珠单抗降低了巨噬细胞水平和血管生成标志物，但未激活T细胞、减少调节性T细胞或改变非应答者中T细胞耗竭标志。二、免疫治疗进展后继续应用免疫治疗的获益上述3项研究为基于免疫治疗的方案后MKI在HCC治疗中的应用提供了初步前瞻性证据，尽管帕博利珠单抗是免疫治疗基石，但是与瑞戈非尼联合使用似乎并未比单独使用MKI带来更多获益。此外，回顾性队列研究表明，在一线免疫治疗失败后，将抗CTLA-4药物添加到抗PD-L1/抗PD-1抑制中可能具有潜在益处。在10例先前接受阿替利珠单抗联合贝伐珠单抗治疗后接受纳武利尤单抗联合伊匹木单抗联合治疗的患者中，3例（30%）患者观察到确认的客观缓解。在另一项纳入32例先前接受抗PD-L1/抗PD-1治疗随后接受纳武利尤单抗联合伊匹木单抗联合治疗的小规模研究中，ORR为22%（7/32）。因此，在一线免疫治疗进展后继续免疫治疗是否有益仍不明确。一项正在进行的Ⅲ期试验（IMbrave251；NCT04770896）也试图回答这个问题，方法是将在使用阿替利珠单抗联合贝伐珠单抗治疗后疾病进展的患者随机分配接受阿替利珠单抗联合仑伐替尼或索拉非尼治疗，或仅接受仑伐替尼或索拉非尼单药治疗。三、免疫治疗后寡进展应用放疗及其他局部区域治疗的获益寡进展是指经系统治疗后残留病灶有限或仅有少量病灶（通常为3~5个）开始进展。该现象在肺癌、结直肠癌和前列腺癌中常见，但在HCC中描述较少。考虑到潜在的第二原发肿瘤可能因肝脏损伤的基础场效应和转移时的基因组差异而出现，所以对寡进展进行治疗可能在HCC中特别有益，这提示不同疾病克隆对免疫治疗的反应可能不同，为部分患者进行局部治疗提供了理论依据。最近的一项回顾性研究报道了54例对免疫治疗有初步持久反应并随后进展的晚期HCC患者的进展模式。其中，2/3的患者在接受免疫治疗后出现寡进展。对于出现寡进展的患者，又有2/3的患者接受了某种形式的局部区域治疗。接受局部区域治疗的患者mOS长于未接受局部区域治疗的患者（46.2 vs. 22.2个月）。综上所述，3项前瞻性Ⅱ期临床研究探索了在免疫治疗进展后应用MKI方案的疗效，并取得了初步成果。此外，新兴的回顾性研究还表明，对于寡进展患者，加用抗CTLA-4或局部区域治疗可能有益。因此，在总结上述最新证据的基础上，研究者总结出了在晚期HCC患者一线免疫治疗后出现疾病进展后的治疗方法（图1），以供大家参考。图.1 晚期HCC患者免疫治疗进展后的拟治疗方法四、前瞻性数据仍缺乏，多学科诊疗是关键当前关于一线免疫治疗失败后不可切除HCC的治疗决策，前瞻性数据仍然有限，但各方向上的证据正在涌现，如改用二线MKI、替代基于免疫治疗的方案（如抗CTLA-4联合方案）以及为寡进展添加局部区域治疗。多项Ⅱ期研究正在进行中，以测试一线免疫治疗失败后这些策略的有效性（表1）。但是，当前由于前瞻性数据仍然稀缺，多学科诊疗仍然是确定每例患者最佳治疗的关键。当然，我们也非常需要生物标志物研究，包括肿瘤微环境分析以及原发性和获得性基因组异质性分析，以便为HCC患者在日益增多的治疗选择中，精准选择最有效的治疗策略。表1. 免疫治疗进展后系统治疗的在研研究参考资料： https://dailynews-ascopubs-org.libproxy1.nus.edu.sg/do/systemic-therapy-hepatocellular-carcinoma-s-next-after-immunotherapy （来源：肿瘤瞭望消化时讯）声明凡署名原创的文章版权属《肿瘤瞭望》所有，欢迎分享、转载。本文仅供医疗卫生专业人士了解最新医药资讯参考使用，不代表本平台观点。该等信息不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议，如果该信息被用于资讯以外的目的，本站及作者不承担相关责任。

ASCO会议免疫疗法临床结果

2024-11-13

·癌度

抗癌新药SY-5007首次人体临床试验数据报道，治疗多种肿瘤产生积极疗效！

由于肿瘤这一疾病的本质是人体细胞基因发生了突变，对于比较常见的肺癌来说，尽管EGFR和ALK的突变频率很高，但是还有其他的驱动基因突变也会导致肺癌的发生，此外其他类型的肿瘤也存在驱动基因突变，今天我们就以RET这个基因突变来说。RET基因所参与的信号通路对于人体正常细胞的迁移、增殖、存活和分化至关重要，如果RET基因突变，会促进细胞生长失控、抗凋亡，并导致肿瘤的发生和转移。对于非小细胞肺癌存在1%到2%的概率有RET基因突变，在髓样甲状腺癌大概有50%存在RET基因突变，乳头状甲状腺癌则有10%到20%存在RET基因突变。针对RET基因突变目前有几款靶向药，包括卡博替尼、凡德他尼、仑伐替尼和索拉非尼，但是这些药物都是多个靶点，所以尽管有一定疗效但临床获益不大。而且会出现剂量限制性脱靶毒性，比如高血压和腹泻，这些影响了患者的生活质量和治疗方案的依从性。最近selpercatinib和pralsetinib的出现部分解决了上述问题，这两款药都获得了美国FDA的批准。今天给大家介绍的SY-5007也是一款RET靶向药，相关的临床研究表明SY-5007的强抑制效力、高选择性，且能减少脱靶毒性，能克服早期治疗的耐药机制。下面就是这款药的一期人体临床试验数据。参考文献刊例图 1、靶向RET的药物SY-5007疗效显著这项临床试验共计招募了122名患者，其中17名患者参加了剂量递增阶段的临床试验，105名患者参加了剂量扩展阶段的临床试验。入组的患者有91名非小细胞肺癌、23名甲状腺髓样癌、7名甲状腺乳头状癌、1名胃癌。 SY-5007的治疗应答率结果如上图所示，在116名可评估疗效的患者中，总体的治疗应答率为57.8%（可评估肿瘤病灶缩小超过30%），如果患者之前没有使用任何治疗则治疗应答率为70%，如果是之前接受过治疗则SY-5007的治疗应答率为51.3%。中位无进展生存时间为21.1个月，如果通过血液样本检测到RET基因突变，则治疗应答率为57.4%，中位无进展生存时间为13.8个月。总体上来说SY-5007的耐受性良好，对于存储RET基因突变的实体瘤患者显示出良好的疗效。 2、启发和讨论上面的内容给大家介绍了一款RET的靶向药SY-5007，通过上面的这个内容，我们可以了解到的信息是很多实体瘤存在RET基因融合突变，注意RET基因的突变形式是与其他基因发生融合，而不是点突变。存在RET基因融合突变的患者目前可以获得的靶向治疗机会还是比较多的，如果存在RET基因的突变，则尽量使用目前美国FDA批准的两款药selpercatinib和pralsetinib，而不是使用一些泛靶点的靶向药，以避免相关的不良反应。此外大家可以关注今天给大家介绍的RET靶向药SY-5007，如果基因检测存在RET基因融合突变，可以考虑联系癌度，参加这类靶向药的临床试验，以争取免费使用靶向药的治疗机会。癌度与吉因加启动的“基因检测人人可及”计划里，仅需要3000元就能检测36个基因，大家可以联系癌度或扫描上面的二维码咨询癌度医学顾问，了解基因检测的相关问题。参考文献： Wei Li, et al, First-in-human, phase 1 dose-escalation and dose-expansion study of a RET inhibitor SY-5007 in patients with advanced RET-altered solid tumors, Signal Transduction and Targeted Therapy volume (2024). 往期推荐抗癌病毒治疗在脑瘤试验中显示出希望，有患者可见病灶消失！遗憾！免疫治疗药物度伐利尤单抗治疗PD-L1高表达肺癌，未能改善总生存时间！最新临床研究：强效新疗法使晚期乳腺癌的无进展生存期翻倍！说癌论道：为什么有些癌症不应该被视作癌症？

临床结果基因疗法

2024-11-07

·GlobeNewswire-Health Care

Kura Oncology Reports Third Quarter 2024 Financial Results

– Topline results from registration-directed trial of ziftomenib in R/R NPM1-mutant AML expected in early 2025; Phase 1 results published in The Lancet Oncology – – Data from 100 patients in Phase 1a dose-escalation study of ziftomenib combined with ven/aza in R/R AML and 7+3 in 1L adverse risk AML to be presented at ASH – – Phase 1b expansion study of ziftomenib in combination with standards of care now enrolling at 600 mg in all cohorts – – Preclinical data support opportunity for ziftomenib in GIST; proof-of-concept study expected to begin in 1H 2025 – – First patient dosed in study of KO-2806 and adagrasib in KRASG12C-mutated NSCLC – – $455.3 million in cash, cash equivalents and investments provide runway into 2027 – – Management to host webcast and conference call today at 4:30 p.m. ET – SAN DIEGO, Nov. 07, 2024 (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 2024 financial results and provided a corporate update. “We approach the end of 2024 in a strong position, with a series of important catalysts ahead,” said Troy Wilson, Ph.D., J.D., President and Chief Executive Officer of Kura Oncology. “First, we look forward to sharing a robust dataset from more than 100 patients in our Phase 1a dose-escalation study of ziftomenib in combination with standards of care in acute myeloid leukemia (AML) at the upcoming American Society of Hematology (ASH) Annual Meeting, followed by topline results from our registration-directed trial of ziftomenib in relapsed/refractory (R/R) NPM1-mutant (NPM1-m) AML early next year. In the meantime, we continue to enroll rapidly across all our ziftomenib studies, further supporting the broad development of our menin inhibitor programs.” Recent Highlights Topline results from registration-directed trial of ziftomenib in early 2025 – In May 2024, Kura completed enrollment of 85 patients in the Phase 2 portion of KOMET-001, a registration-directed clinical trial of its menin inhibitor, ziftomenib, in patients with R/R NPM1-m AML. Ziftomenib is the first and only investigational therapy to be granted Breakthrough Therapy Designation (BTD) for the treatment of R/R NPM1-m AML, which accounts for approximately 30% of new AML cases annually and represents a disease of significant unmet need for which no approved targeted therapy exists. Results from the Phase 1 portion of KOMET-001 were recently published in the leading clinical oncology journal, The Lancet Oncology.Data from Phase 1a dose-escalation study of ziftomenib at ASH – Two abstracts reporting preliminary data from the Phase 1a dose-escalation study of ziftomenib in combination with standards of care in patients with NPM1-m and KMT2A-rearranged (KMT2A-r) AML have been accepted for presentation at the ASH Annual Meeting in December. As of the June 21, 2024 data cutoff, the abstracts continue to support a potential best-in-class safety and tolerability profile for ziftomenib, as well as robust and durable activity in combination with standards of care, including venetoclax plus azacitidine (ven/aza) as well as cytarabine plus daunorubicin (7+3). Kura expects to present a more mature dataset from more than 100 patients in the Phase 1a dose-escalation study in the presentations at ASH.Phase 1b expansion study of ziftomenib now enrolling in all cohorts – All four cohorts in the Phase 1a dose-escalation study have cleared the highest dose and advanced into the Phase 1b expansion study at 600 mg. The Phase 1b expansion study includes multiple combination cohorts, including ziftomenib plus ven/aza in newly diagnosed NPM1-m or KMT2A-r AML and ziftomenib plus 7+3 in newly diagnosed NPM1-m or KMT2A-r AML without qualification for high-risk disease. Each of the seven combination cohorts is expected to enroll at least 20 patients. A total of 45 patients have already enrolled in the study since the first dose-expansion cohort opened in August 2024. The Company anticipates sharing preliminary data from the Phase 1b expansion study at a medical meeting in 2025.Preclinical data support opportunity for ziftomenib in GIST – Last month, at the EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Barcelona, Kura reported preclinical data supporting the combination of ziftomenib and imatinib for the treatment of advanced gastrointestinal stromal tumors (GIST). The combination showed unexpectedly robust and durable antitumor activity in both imatinib-sensitive and imatinib-resistant GIST patient-derived xenograft models, and in all cases was significantly superior to imatinib monotherapy. The Company received FDA clearance of its Investigational New Drug application for ziftomenib for the treatment of advanced GIST in August and expects to initiate a proof-of-concept study in the first half of 2025 evaluating ziftomenib and imatinib in patients with advanced GIST who have failed imatinib.First patient dosed in study of KO-2806 and adagrasib in KRASG12C-mutated NSCLC – In August 2024, Kura began dosing patients in its study of KO-2806, a next-generation farnesyl transferase inhibitor (FTI), in combination with adagrasib in KRASG12C-mutated non-small cell lung cancer (NSCLC). The Company’s findings suggest that combining KO-2806 with adagrasib may drive tumor regressions and enhance both duration and depth of antitumor response in preclinical models of KRASG12C-mutated NSCLC. The study of KO-2806 and adagrasib is supported by a clinical collaboration and supply agreement with Mirati, now a Bristol Myers Squibb company.Preclinical data support potential for menin inhibitor in diabetes – In June 2024, Kura reported data showing that ziftomenib induces insulin production, improves insulin sensitivity and reduces insulin resistance in a preclinical in vivo model of type 2 diabetes. Ziftomenib demonstrated meaningful levels of glycemic control, including reduced fasting blood glucose levels and %HbA1C within 27 days, as well as consistent improvement in both insulin sensitivity and insulin production. The data were presented at the American Diabetes Association Scientific Sessions in Orlando. The Company expects to nominate a next generation menin inhibitor candidate targeting diabetes in the first half of 2025. Financial Results Research and development expenses for the third quarter of 2024 were $41.7 million, compared to $29.3 million for the third quarter of 2023.General and administrative expenses for the third quarter of 2024 were $18.2 million, compared to $13.1 million for the third quarter of 2023.Net loss for the third quarter of 2024 was $54.4 million, compared to a net loss of $38.6 million for the third quarter of 2023. This included non-cash share-based compensation expense of $8.3 million, compared to $7.1 million for the same period in 2023.As of September 30, 2024, Kura had cash, cash equivalents and short-term investments of $455.3 million, compared to $424.0 million as of December 31, 2023.Based on its operating plan, management expects that cash, cash equivalents and short-term investments will fund current operations into 2027. Forecasted Milestones Present updated data from the KOMET-007 trial of ziftomenib in combination with ven/aza and 7+3 at ASH in December 2024.Report topline results from the KOMET-001 registration-directed trial of ziftomenib in NPM1-mutant R/R AML in early 2025.Present preliminary data from the Phase 1b expansion portion of KOMET-007 at a medical meeting in 2025.Initiate proof-of-concept study evaluating ziftomenib and imatinib in patients with advanced GIST in the first half of 2025.Nominate a next generation menin inhibitor development candidate targeting diabetes in the first half of 2025.Identify the maximum tolerated dose for KO-2806 as a monotherapy in the second half of 2024.Initiate one or more expansion cohorts for the combination of KO-2806 and cabozantinib in renal cell carcinoma in the first half of 2025.Present data from the KURRENT-HN trial of tipifarnib in combination with alpelisib in PIK3CA-dependent head and neck squamous cell carcinoma (HNSCC) in the first half of 2025. Conference Call and Webcast Kura’s management will host a webcast and conference call at 4:30 p.m. ET / 1:30 p.m. PT today, November 7, 2024, to discuss the financial results for the third quarter 2024 and to provide a corporate update. The live call may be accessed by dialing (800) 225-9448 for domestic callers and (203) 518-9708 for international callers and entering the conference ID: KURAQ3. A live webcast and archive of the call will be available online from the investor relations section of the company 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 consists of small molecule drug candidates that target cancer signaling pathways. Ziftomenib, a once-daily, oral drug candidate targeting the menin-KMT2A protein-protein interaction, has received BTD for the treatment of R/R NPM1-m AML. Kura has completed enrollment in a Phase 2 registration-directed trial of ziftomenib in R/R NPM1-m AML (KOMET-001). The Company is also conducting a series of clinical trials to evaluate ziftomenib in combination with current standards of care in newly diagnosed and R/R NPM1-m and KMT2A-r AML. Kura is evaluating KO-2806, a next-generation FTI, in a Phase 1 dose-escalation trial as a monotherapy and in combination with targeted therapies (FIT-001). Tipifarnib, a potent and selective FTI, is currently in a Phase 1/2 trial in combination with alpelisib for patients with PIK3CA-dependent HNSCC (KURRENT-HN). For additional information, please visit Kura’s website at www.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, the efficacy, safety and therapeutic potential of Kura’s product candidates, ziftomenib, KO-2806 and tipifarnib, progress and expected timing of Kura’s drug development programs and clinical trials and submission of regulatory filings, the presentation of data from clinical trials, plans regarding regulatory filings and future clinical trials, the strength of Kura’s balance sheet and the sufficiency of cash, cash equivalents and short-term investments to fund its current operating plan into 2027. Factors that may cause actual results to differ materially include 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, the risk that Kura may not obtain approval to market its product candidates, uncertainties associated with performing clinical trials, regulatory filings, applications 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, 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. KURA ONCOLOGY, INC. Statements of Operations Data (unaudited) (in thousands, except per share data) Three Months Ended Nine Months Ended September 30, September 30, 2024 2023 2024 2023 Operating Expenses: Research and development $41,705 $29,328 $117,700 $82,702 General and administrative 18,179 13,145 53,040 36,340 Total operating expenses 59,884 42,473 170,740 119,042 Other income, net 5,480 3,871 15,974 9,197 Net loss $(54,404) $(38,602) $(154,766) $(109,845)Net loss per share, basic and diluted $(0.63) $(0.50) $(1.80) $(1.53)Weighted average number of shares used in computing net loss per share, basic and diluted 86,950 77,241 85,834 71,845 KURA ONCOLOGY, INC. Balance Sheet Data (unaudited) (in thousands) September 30, December 31, 2024 2023 Cash, cash equivalents and short-term investments $455,297 $423,957 Working capital 422,817 397,218 Total assets 478,837 448,935 Long-term liabilities 14,694 16,399 Accumulated deficit (876,205) (721,439)Stockholders’ equity 423,771 397,273 Contacts Investors:Pete De SpainExecutive Vice President, Investor Relations &Corporate Communications(858) 500-8833pete@kuraoncology.com Media:Cassidy McClainVice PresidentInizio Evoke Comms(619) 849-6009cassidy.mcclain@inizioevoke.com

临床1期临床2期财报突破性疗法

100 项与苹果酸卡博替尼相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D10095	苹果酸卡博替尼	L01XE26	DB08875

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
甲状腺癌	美国	Exelixis, Inc.	2021-09-17
分化型甲状腺癌	韩国	Ipsen Ltd.	2017-09-26
肾细胞癌	韩国	Ipsen Ltd.	2017-09-26
肝细胞癌	欧盟	Ipsen Pharma SAS	2016-09-09
肝细胞癌	冰岛	Ipsen Pharma SAS	2016-09-09
肝细胞癌	列支敦士登	Ipsen Pharma SAS	2016-09-09
肝细胞癌	挪威	Ipsen Pharma SAS	2016-09-09
晚期肾细胞癌	美国	Exelixis, Inc.	2016-04-25
甲状腺髓样癌	美国	Exelixis, Inc.	2012-11-29

未上市

10 条进展最快的记录,

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
胰腺神经内分泌肿瘤	申请上市	美国	Exelixis, Inc.	2024-08-06
实体瘤	申请上市	中国	江苏豪森药业集团有限公司	2020-09-28
难治性分化型甲状腺癌	临床3期	-	National Cancer Institute	2024-09-13
转移性骨肉瘤	临床3期	-	National Cancer Institute	2023-01-13
不能切除的骨肉瘤	临床3期	-	National Cancer Institute	2023-01-13
晚期尿路上皮癌	临床3期	美国	National Cancer Institute	2022-06-03
晚期尿路上皮癌	临床3期	加拿大	National Cancer Institute	2022-06-03
膀胱癌	临床3期	美国	National Cancer Institute	2022-06-03
膀胱癌	临床3期	加拿大	National Cancer Institute	2022-06-03
转移性尿道尿路上皮癌	临床3期	美国	National Cancer Institute	2022-06-03

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临床结果

适应症

分期

评价

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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


NCT03375320 (CABINET \| A021602, CTgov)	临床3期	高分化胰腺内分泌肿瘤 \| 胰腺神经内分泌肿瘤 \| 类癌 ... 更多	298	Cabozantinib S-malate (Arm Ia (Cabozantinib S-malate, Extra-pancreatic NET Cohort [epNET]))	廠選淵願簾願簾顧蓋淵(淵鹽壓艱構製艱齋襯遞) = 鹽衊鹹簾鹹顧網夢齋範鏇餘鏇願顧網願選膚鏇 (積夢鹹觸遞鹽蓋醖鏇齋, 簾夢壓鬱製簾齋鬱簾襯 ~ 網窪鏇蓋廠襯窪遞繭蓋) 更多	-	2024-10-16
				Placebo (Arm IIa (Placebo, Extra-pancreatic NET Cohort [epNET]))	廠選淵願簾願簾顧蓋淵(淵鹽壓艱構製艱齋襯遞) = 鏇願齋壓範製鑰顧夢齋鏇餘鏇願顧網願選膚鏇 (積夢鹹觸遞鹽蓋醖鏇齋, 壓艱餘遞鑰窪廠願鏇餘 ~ 醖鬱壓廠觸簾願構糧憲) 更多
NCT05200143 (CTgov)	临床2期	难治性黑色素瘤 \| 皮肤黑色素瘤	4	Ipilimumab+Cabozantinib	廠襯糧鹹鬱獵鬱淵鑰鹹(窪鬱鑰網餘製顧鬱鬱構) = 衊糧艱襯鑰醖鑰製淵廠夢衊夢願範鬱糧餘觸窪 (製簾鑰齋獵獵廠衊鏇憲, 廠鹹鑰築壓糧艱鑰範壓 ~ 構衊鹽鑰鑰襯艱窪衊鹹) 更多	-	2024-09-19
NCT03375320 (CABINET \| A021602, ESMO2024) 人工标引	临床3期	晚期神经内分泌肿瘤	298	cabozantinib (locally advanced or metastatic extra-pancreatic neuroendocrine tumors)	積廠壓構顧願艱壓觸鏇(網襯鑰糧築壓蓋鬱淵製) = 顧選齋獵窪簾鏇築鏇遞簾憲觸願構夢網糧夢願 (鬱構鑰窪鑰觸鏇構顧淵 ) 更多	积极	2024-09-16
				Placebo (locally advanced or metastatic extra-pancreatic neuroendocrine tumors)	積廠壓構顧願艱壓觸鏇(網襯鑰糧築壓蓋鬱淵製) = 廠壓選淵襯鏇網積積鹽簾憲觸願構夢網糧夢願 (鬱構鑰窪鑰觸鏇構顧淵 ) 更多
NCT03375320 (CABINET, Pubmed \| N Engl J Med) 人工标引	临床3期	晚期神经内分泌肿瘤	203	Cabozantinib 60 mg	餘鑰築廠顧壓壓糧襯壓(夢鬱襯製築積獵鏇範簾) = 鬱願鹽淵夢襯鹹繭獵淵襯憲淵膚鹹襯艱願遞觸 (選蓋鏇鑰鑰鹽範繭鬱觸 ) 更多	积极	2024-09-16
				Placebo	餘鑰築廠顧壓壓糧襯壓(夢鬱襯製築積獵鏇範簾) = 蓋廠遞襯膚簾襯簾願醖襯憲淵膚鹹襯艱願遞觸 (選蓋鏇鑰鑰鹽範繭鬱觸 ) 更多
NCT04413123 (ESMO2024) 人工标引	临床2期	晚期肾细胞癌二线	39	cabozantinib+nivolumab+ipilimumab	願築鑰積獵蓋積鏇鏇蓋(鹹構簾觸廠鑰範壓網膚) = 遞齋鏇獵廠範夢醖簾膚窪淵鹹顧醖鹽膚簾餘網 (鏇顧壓襯鬱願夢淵齋鹹, 12% ~ 31) 更多	积极	2024-09-15
NCT04446117 (CONTACT-02, BusinessWire \| NEWS) 人工标引	临床3期	转移性去势抵抗性前列腺癌	575	cabozantinib+atezolizumab	製窪膚構範鬱窪積鹹窪(鹹鏇鏇範獵築簾鬱繭顧) = 製積積膚膚積製繭鬱憲選獵簾夢範製鑰網糧鹹 (構製築製鑰簾淵築壓淵, 13.4 ~ 16.7) 更多	不佳	2024-09-15
				novel hormonal therapy	製窪膚構範鬱窪積鹹窪(鹹鏇鏇範獵築簾鬱繭顧) = 醖醖齋蓋鹹糧壓艱遞膚選獵簾夢範製鑰網糧鹹 (構製築製鑰簾淵築壓淵, 13.0 ~ 18.5) 更多
NCT03945773 (CaboPoint, ESMO2024) 人工标引	临床2期	晚期肾细胞癌二线	127	Cabozantinib 60 mg/day after 1L nivolumab + ipilimumab	範膚糧構範鬱簾鹽製遞(壓鹹鹹積鏇築醖簾簾製) = 壓醖齋遞選憲簾積糧夢壓範顧簾鏇衊鏇簾積廠 (鹽衊鬱簾遞鑰齋願艱構, 29.6 ~ 52.1) 更多	积极	2024-09-15
				Cabozantinib 60 mg/day after 1L CPI + VEGF-targeted therapy	範膚糧構範鬱簾鹽製遞(壓鹹鹹積鏇築醖簾簾製) = 壓衊艱襯鬱窪醖艱遞顧壓範顧簾鏇衊鏇簾積廠 (鹽衊鬱簾遞鑰齋願艱構, 14.6 ~ 43.9) 更多
NCT03824691 (ARCADIA, ESMO2024) 人工标引	临床2期	尿路上皮癌	61	Cabozantinib+durvalumab	膚窪鬱鑰鬱範餘窪膚壓(築顧鑰醖艱鬱積網憲鹽) = 醖製衊網壓窪糧膚壓積襯淵憲窪鹽窪窪艱憲壓 (糧鹽膚餘鬱膚糧簾鑰襯, 5.1 ~ NR) 更多	积极	2024-09-15
NCT03824691 (ARCADIA, ESMO2024) 人工标引	临床2期	尿路上皮癌	61	Cabozantinib+durvalumab	蓋選製壓憲鏇淵齋齋鏇(網艱廠醖選齋遞積餘蓋) = 鏇構鬱顧獵範艱顧鹽鹽糧範糧壓鏇鑰構顧網鏇 (積壓繭廠遞蓋選夢範鬱, 7.1 ~ 25.5) 更多	积极	2024-09-15
NCT04524208 (CABONEN, ESMO2024) 人工标引	临床2期	神经内分泌肿瘤	32	Cabozantinib	廠鹽鹽鹽願鹹顧築窪鹽(窪餘醖憲醖築醖鏇顧窪) = 醖蓋構膚積築糧繭願襯積齋醖齋範衊襯醖鬱積 (網網廠積願窪顧餘構選 ) 更多	积极	2024-09-13