Phase 1 Trial to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of GP-2250 With Gemcitabine in Advanced Unresectable or Metastatic Pancreatic Adenocarcinoma Following Progression on 5-FU-based Chemotherapy

This is a phase 1 first in human, dose escalation trial of GP-2250 administered in combination with gemcitabine in subjects with advanced pancreatic cancer previously treated with 5-fluorouracil-based chemotherapy.
Prior radiosensitization with gemcitabine, the use of 5-fluorouracil, FOLFIRINOX or Nab-paclitaxel/gemcitabine in the neoadjuvant setting, and prior pancreaticoduodenectomy (Whipple procedure) is allowed. If prior treatment with gemcitabine was at therapeutic doses, a minimum of 3 months must have elapsed since the end of such treatment.
As a precursor to 5-FU use of capecitabine-based chemotherapy is also permitted.

开始日期2019-01-14

申办/合作机构

Geistlich Pharma AG

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100 项与 Misetionamide 相关的临床结果

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100 项与 Misetionamide 相关的转化医学

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100 项与 Misetionamide 相关的专利（医药）

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项与 Misetionamide 相关的文献（医药）

2024-08-01·Cancer Medicine

Mechanism and rational combinations with GP‐2250, a novel oxathiazine derivative, in ovarian cancer

Article

作者: Lankenau Ahumada, Adrian ; Lee, Sanghoon ; Kim, Mark S. ; Glassman, Deanna ; Foster, Katherine ; Coleman, Robert L. ; Joseph, Robiya ; Sood, Anil K. ; Bayraktar, Emine ; Jennings, Nicholas B. ; Handley, Katelyn F.

AbstractBackgroundGP‐2250, a novel analog of taurultam (TRLT), has emerged as a potent anti‐neoplastic drug; however, the mechanisms underlying its effects are not well understood. Here, we investigated the mechanism of action and the biological effects of GP‐2250 using in vitro and in vivo models.MethodsWe carried out a series of in vitro (MTT assay, Annexin V/PI assay, colony formation assay, reverse‐phase protein array [RPPA], and HRLC/IC analysis) to determine the biological activity of GP‐2250 and investigate the mechanism of action. In vivo experiments were carried out to determine the therapeutic efficacy of GP‐2250 alone and in combination with standard‐of‐care drugs (e.g., paclitaxel, cisplatin, topotecan, and poly ADP‐ribose polymerase [PARP] inhibitors).ResultsWe investigated the cytotoxic effect of GP‐2250 in 10 ovarian cancer cell lines and found GP‐2250 combined with a PARP inhibitor had the greatest synergy. RPPA revealed that GP‐2250 inhibited hypoxia‐inducible factor‐1α, AKT, and mammalian target of rapamycin (mTOR) activation and expression. High‐resolution mass spectrometry revealed that hexokinase2 activity and protein expression were significantly reduced by GP‐2250 exposure. Furthermore, GP‐2250 reduced glycolysis and ATP synthesis in cancer cells. An in vivo pharmacodynamic experiment using the OVCAR8 mouse model demonstrated that 500 mg/kg GP‐2250 was effective in downregulating AKT and mTOR activation and expression. In the in vivo therapy experiment using an orthotopic mouse model, a combination of GP‐2250 with either PARP inhibitors or bevacizumab showed a significant reduction of tumor weights and nodules compared to those treated with a vehicle, control IgG groups, or monotherapy groups.ConclusionsTaken together, our data indicate that GP‐2250 exerts profound effects on tumor metabolism and, in combination with PARP inhibitors or bevacizumab, showed promising anti‐tumor efficacy. These findings could have implications for the clinical development of GP‐2250.

2023-10-19·International journal of molecular sciences

In Vitro Experiments on the Effects of GP-2250 on BRAF-Mutated Melanoma Cell Lines and Benign Melanocytes.

Article

作者: Harnischfeger, Friederike ; Buchholz, Marie ; Müller, Thomas ; Skrygan, Marina ; Gambichler, Thilo ; Majchrzak-Stiller, Britta ; Braumann, Chris

Enhanced glycolysis (Warburg effect) driven by the BRAF oncogene, dysregulated GAPDH expression, and activation of the PI3K/AKT/mTOR signaling pathway may significantly contribute to the resistance-targeted therapy of BRAF-mutated melanomas. Therefore, we aimed to study for the first time the anti-tumor activity of the GAPDH inhibitor GP-2250 in BRAF-mutated melanoma cell lines and benign melanocytes. We employed three melanoma cell lines and one primary melanocyte cell line (Ma-Mel-61a, Ma-Mel-86a, SH-4 and ATCC-PCS-200-013, respectively), which were exposed to different GP-2250 doses. GP-2250's effects on cell proliferation and viability were evaluated by means of the BrdU and MTT assays, respectively. The RealTime-Glo Annexin V Apoptosis and Necrosis Assay was performed for the evaluation of apoptosis and necrosis induction. RT-PCR and western blotting were implemented for the determination of AKT and STAT3 gene and protein expression analyses, respectively. The melanoma cell lines showed a dose-dependent response to GP-2250 during BrDU and MTT testing. The RealTime-Glo Annexin V assay revealed the heterogenous impact of GP-2250 on apoptosis as well as necrosis. With respect to the melanoma cell lines Ma-Mel-86a and SH-4, the responses and dosages were comparable to those used for the MTT viability assay. Using the same dose range of GP-2250 administered to melanoma cells, however, we observed neither the noteworthy apoptosis nor necrosis of GP-2250-treated benign melanocytes. The gene expression profiles in the melanoma cell lines for AKT and STAT3 were heterogenous, whereby AKT as well as STAT3 gene expression were most effectively downregulated using the highest GP-2250 doses. Immunoblotting revealed that there was a time-dependent decrease in protein expression at the highest GP-2250 dose used, whereas a time- as well as dose-dependent AKT decrease was predominantly observed in Ma-Mel-61a. The STAT3 protein expression of Ma-Mel-86a and SH-4 was reduced in a time-dependent pattern at lower and moderate doses. STAT3 expression in Ma-Me-61a was barely altered by GP-2250. In conclusion, GP-2250 has anti-neoplastic effects in BRAF-mutated melanoma cell lines regarding tumor cell viability, proliferation, and apoptosis/necrosis. GP-2250 is able to downregulate the gene and protein expression of aberrant tumorigenic pathways in melanoma cell lines. Since GP-2250 is a GAPDH inhibitor, the substance may be a promising combination therapy for tumors presenting the Warburg effect, such as melanoma.

2023-09-01·Journal of cancer research and clinical oncology

The effect of GP-2250 on cultured virus-negative Merkel cell carcinoma cells: preliminary results.

Article

作者: Becker, Jürgen C ; Buchholz, Marie ; Majchrzak-Stiller, Britta ; Gambichler, Thilo ; Braumann, Chris ; Abu Rached, Nessr ; Uhl, Waldemar ; Peters, Ilka ; Strotmann, Johanna ; Müller, Thomas

BACKGROUNDEven in the novel immunotherapy era, Merkel cell carcinoma (MCC) remains challenging in its treatment. Apart from Merkel cell polyomavirus (MCPyV) associated MCC, this cancer is linked in about 20% of cases to ultraviolet-induced mutational burden frequently causing aberrations in Notch and PI3K/AKT/mTOR signalling pathways. The recently developed agent GP-2250 is capable to inhibit growth of cells of different cancers, including pancreatic neuroendocrine tumors. The objective of the present study was to investigate the effects of GP-2250 on MCPyV-negative MCC cells.METHODSMethods We employed three cell lines (MCC13, MCC14.2, MCC26) which were exposed to different GP-2250doses. GP-2250's effects on cell viability, proliferation, and migration were evaluated by means of MTT, BrdU, and scratch assays, respectively. Flow cytometry was performed for the evaluation of apoptosis and necrosis. Western blotting was implemented for the determination of AKT, mTOR, STAT3, and Notch1 protein expression.RESULTSCell viability, proliferation, and migration decreased with increasing GP-2250 doses. Flow cytometry revealed a dose response to GP-2250 in all three MCC cell lines. While the viable fraction decreased, the share of necrotic and in a smaller amount the apoptotic cells increased. Regarding Notch1, AKT, mTOR, and STAT3 expression a comparatively time- and dose-dependent decrease of protein expression in the MCC13 and MCC26 cell lines was observed. By contrast, Notch1, AKT, mTOR, and STAT3 expression in MCC14.2 was scarcely altered or even increased by the three dosages of GP-2250 applied.CONCLUSIONSThe present study indicates GP-2250 having anti-neoplastic effects in MCPyV-negative tumor cells in regard to viability, proliferation, and migration. Moreover, the substance is capable of downregulating protein expression of aberrant tumorigenic pathways in MCPyV-negative MCC cells.

项与 Misetionamide 相关的新闻（医药）

2024-10-13

·药明康德

100%患者获临床缓解的CAR-T疗法；晚期癌症疾病控制率达92%的TCR-T疗法…… | 一周盘点

▎药明康德内容团队编辑本期看点 1. T细胞受体T细胞（TCR-T）疗法IMA203在一项1b期临床试验中令92%转移性黑色素瘤患者的疾病获得控制，且患者的中位缓解持续时间（DOR）超过一年。 2. B细胞成熟抗原（BCMA）靶向自体嵌合抗原受体（CAR）-T细胞疗法Ribrecabtagene autoleucel（DRL-1801）用于治疗复发/难治性多发性骨髓瘤患者的1期临床试验结果亮眼，首批8名接受治疗的患者均获得了临床缓解。 3. 用于治疗胶质母细胞瘤（GBM）的树突状细胞疫苗DOC1021相比于标准治疗（SOC）有望大幅延长患者的中位总生存期（OS）。药明康德内容团队整理 IMA203：公布1b期临床试验数据 Immatics公布了其在研TCR-T疗法IMA203用以治疗转移性黑色素瘤患者的最新1b期临床数据，这些患者先前接受过大量治疗。IMA203是由Immatics专有的ACTengine平台所开发的TCR-T细胞疗法，靶向由HLA-A*02呈递的黑素瘤抗原PRAME。PRAME是一种在各种实体瘤中经常表达的蛋白质，因此IMA203具潜力治疗广泛的癌症患者群体。此次公布的结果显示，92%患者的疾病获得控制且患者的中位DOR超过一年。根据此积极数据，Immatics预定在今年12月启动SUPRAME注册性3期试验，预计病患招募将于2026年完成，并在2026年初进行预定的中期分析。 Ribrecabtagene autoleucel（DRL-1801）：公布1期临床试验数据 Aurigene Oncology公司宣布其新型BCMA靶向自体CAR-T细胞疗法Ribrecabtagene autoleucel（DRL-1801）用于治疗复发/难治性多发性骨髓瘤的1期临床试验中首批8名患者的初步结果。所有患者都接受过大量的前期治疗，中位治疗线数为5.5线。大多数患者此前也曾接受过移植手术，并在移植后出现疾病进展。结果显示，100%的患者获得了临床缓解，其中有5名（62.5%）患者获得了严格的完全缓解（CR）。安全性方面，所有患者均未出现高级别的细胞因子释放综合征（CRS）或神经毒性。 DOC1021：公布1期临床试验的中期数据 Diakonos Oncology公司公布了其树突状细胞疫苗DOC1021用于治疗胶质母细胞瘤患者的1期开放标签试验的中期分析结果。该公司的树突状细胞疫苗由患者自身的免疫细胞与从肿瘤样本中提取的RNA和蛋白质结合制成。这种独特的方法可以靶向完整的癌症抗原谱，而无需进行任何基因修饰。通过利用天然的免疫信号通路，这种策略使免疫系统能将癌细胞视同受病毒感染的细胞一样进行识别和清除。此次公布的结果显示，15例患有挑战性肿瘤、MGMT未甲基化（通常预后不良）患者中有14例存活超过12个月。目前，中位随访时间为16个月，中位OS尚未达到。Kaplan-Meier（KM）分析将接受DOC1021治疗的患者与接受完整SOC的年龄匹配历史对照组患者进行比较，两组在统计学上具有差异（p=0.03）。KM预测接受DOC1021治疗的患者的OS为19.7个月，而接受SOC的未甲基化GBM患者的预期OS为12.7个月。安全性方面，没有剂量限制性毒性或令人担忧的严重不良事件（SAE）。 VIP943：公布1期临床试验数据 Vincerx Pharma公司公布了其抗体偶联药物（ADC）VIP943治疗复发/难治性急性髓系白血病（AML）、高危骨髓增生异常综合征（HR-MDS）和B细胞急性淋巴细胞白血病（B-ALL）的1期临床试验的结果。VIP943由抗CD123抗体、一种在细胞内切割的独特连接子和一种新型驱动蛋白纺锤体蛋白抑制剂（KSPi）有效载荷组成。Vincerx的CellTrapper技术可确保KSPi有效载荷积聚在靶细胞中，限制非靶细胞、非分裂细胞的吸收，从而减少非特异性释放。该1期剂量递增研究共招募了22名患者，他们很少对单一疗法产生应答。9名患者（6名AML患者和3名HR-MDS患者）至少接受了3次有效剂量的VIP943治疗。截至目前，1名复发性AML患者获得了完全缓解伴血液学不完全恢复（CRi），1名HR-MDS患者获得了完全缓解伴较少血液学恢复（CRL）。截至2024年8月的数据，VIP943显示出良好的安全性和耐受性，没有报告剂量限制性毒性，SAE与预期一致。 VK0214：公布1b期临床试验数据 Viking Therapeutics公司公布了其新型甲状腺激素受体β（TRβ）小分子激动剂VK0214在X-连锁肾上腺白质营养不良（X-ALD）患者中进行的1b期临床试验的积极数据。X-ALD是一种罕见的致命代谢性疾病，由ABCD1基因突变引起，这种突变会导致肾上腺脑白质营养不良蛋白（ALDP）功能障碍，从而引起脂肪酸的异常累积。临床前研究表明，甲状腺激素受体β型可以调节ABCD2相关基因的表达，ABCD2能够编码一种称为肾上腺脑白质营养不良相关蛋白（ADLRP）的代偿转运体，通过增加ABCD2表达可以使特定脂肪酸水平恢复正常。此次公布的研究结果表明，在为期28天的研究期间，VK0214每天用药一次的安全性和耐受性良好。此外，与安慰剂相比，接受VK0214治疗患者血浆中的超长链脂肪酸（VLCFAs）和其他血脂水平明显降低。 ▲VK0214治疗28天后患者的VLCFA与基线相比的变化（图片来源：参考资料[5]） ▲VK0214治疗28天后患者的其他血脂与基线相比的变化（图片来源：参考资料[5]） Paxalisib：公布1期临床试验的新数据 Kazia Therapeutics公司公布其口服PI3K/mTOR双抑制剂paxalisib联用放射疗法治疗PI3K通路突变实体瘤脑转移（BM）或软脑膜转移（LM）患者的1期临床试验的数据。此次公布的结果显示，paxalisib联用放疗总体耐受性良好。研究中最常报告的不良反应是恶心、呕吐和高血糖。接受45 mg paxalisib联用放疗患者中有67%获得了部分缓解（PR），接受最大耐受剂量治疗的患者中有超过三分之二的人获得了颅内缓解，这与单独使用全脑放疗的历史缓解率相比毫不逊色。 ELVN-001：公布1期临床试验的新数据 Enliven Therapeutics公司公布其小分子激酶抑制剂ELVN-001治疗复发/难治性或对现有酪氨酸激酶抑制剂（TKI）不耐受的慢性髓系白血病（CML）患者的1期临床试验的积极数据。ELVN-001是一种强效、高选择性、潜在“best-in-class”的小分子激酶抑制剂，专门针对CML患者的致癌驱动因子BCR-ABL融合蛋白。ELVN-001还具有针对耐药性最强的BCR-ABL1耐药突变体T315I和其他已知耐药突变体的活性。截至2024年6月25日的数据，ELVN-001的耐受性保持良好，没有患者减少剂量，未报告≥3级治疗相关的非血液学毒性反应。第24周时，患者的初始累积主要分子缓解（MMR）率为44%（8/18），与已获批的BCR-ABL1酪氨酸激酶抑制剂在1期临床试验中的数据相比具有优势。 Camonsertib：公布1期联合治疗试验数据 Repare Therapeutics公司公布了潜在”best-in-class”口服小分子ATR抑制剂camonsertib结合姑息性放疗，治疗携带ATM突变转移性肿瘤的1期临床试验数据。该试验纳入了17例携带ATM突变的转移性肿瘤患者，其中12人携带致病性ATM基因突变，5人携带ATM基因突变的意义不明变异（VUS）。这些患者的原发性癌症组织学来源包括胃肠道（n=5）、胰腺（n=5）、乳腺癌（n=2）、肺（n=2）、膀胱（n=2）和甲状腺（n=1）。此次公布的结果显示，2个月时，致病性ATM突变组有2例CR、5例PR和4例疾病稳定（SD）患者，而VUS组有1例PR和4例SD患者。6个月时，在9名可评估患者中，致病性ATM突变组有2例CR、4例PR和1例SD患者，而VUS组有1例SD和1例疾病进展患者。该早期临床数据表明camonsertib联合放疗治疗有可能对携带致病性ATM突变的肿瘤患者进行放射增敏，从而获得更高的临床益处。 Misetionamide：公布1期临床试验的中期数据 Panavance Therapeutics公司公布了其小分子疗法misetionamide（GP-2250）联用吉西他滨治疗晚期不可切除或转移性胰腺导管腺癌患者1期临床试验的中期数据。Misetionamide具有独特的作用机制，可抑制两种致癌转录因子c-MYC和NFκB。此次公布的结果显示，与单独使用吉西他滨的历史结果相比，接受misetionamide联用吉西他滨治疗患者的无进展生存期更长，约40%的患者达到PR或SD。此外，misetionamide联用吉西他滨的安全性良好。 ▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放参考资料（可上下滑动查看） [1] Vincerx Reports Positive Initial Clinical Data from Ongoing VIP943 Phase 1 Dose-Escalation Study and Provides Pipeline and Corporate Updates. Retrieved October 11, 2024, from https://www.globenewswire.com/news-release/2024/10/07/2959307/0/en/Vincerx-Reports-Positive-Initial-Clinical-Data-from-Ongoing-VIP943-Phase-1-Dose-Escalation-Study-and-Provides-Pipeline-and-Corporate-Updates.html [2] CNS 2024 Conference Presentation: Diakonos Oncology’s Autologous Dendritic Cell Vaccine (DOC1021) Yields 93% 12-Month Survival for Glioblastoma Patients. Retrieved October 11, 2024, from https://www.diakonosoncology.com/news/cns-2024-conference-presentation-diakonos-oncologys-autologous-dendritic-cell-vaccine-doc1021-yields-93-12-month-survival-for-glioblastoma-patients/ [3] Enliven Therapeutics Announces Positive Data Update from Phase 1 Clinical Trial of ELVN-001 in Chronic Myeloid Leukemia. Retrieved October 11, 2024, from https://www.globenewswire.com/news-release/2024/09/28/2954762/0/en/Enliven-Therapeutics-Announces-Positive-Data-Update-from-Phase-1-Clinical-Trial-of-ELVN-001-in-Chronic-Myeloid-Leukemia.html [4] Kazia Therapeutics Announces Presentation of Promising Phase I Data Evaluating Concurrent Paxalisib and Radiation Therapy in Patients with Solid Tumor Brain Metastases or Leptomeningeal Metastases Harboring PI3K Pathway Mutations at the American Society for Radiation Oncology 66th Annual Meeting. Retrieved October 11, 2024, from https://www.prnewswire.com/news-releases/kazia-therapeutics-announces-presentation-of-promising-phase-i-data-evaluating-concurrent-paxalisib-and-radiation-therapy-in-patients-with-solid-tumor-brain-metastases-or-leptomeningeal-metastases-harboring-pi3k-pathway-mutations--302265538.html [5] Viking Therapeutics Announces Results from Phase 1b Clinical Trial of VK0214 in Patients with X-ALD. Retrieved October 11, 2024, from https://www.prnewswire.com/news-releases/viking-therapeutics-announces-results-from-phase-1b-clinical-trial-of-vk0214-in-patients-with-x-ald-302270769.html [6] Repare Therapeutics Announces Phase 1 Data Highlighting Camonsertib in Combination with Radiotherapy Treatment Presented at the ASTRO Annual Meeting. Retrieved October 11, 2024, from https://ir.reparerx.com/news-releases/news-release-details/repare-therapeutics-announces-phase-1-data-highlighting [7] Panavance Therapeutics Provides Update on Phase 1 Clinical Trial of Misetionamide in Pancreatic Cancer at 2024 Visceral Medicine Congress. Retrieved October 11, 2024, from https://www.globenewswire.com/news-release/2024/10/09/2960394/0/en/Panavance-Therapeutics-Provides-Update-on-Phase-1-Clinical-Trial-of-Misetionamide-in-Pancreatic-Cancer-at-2024-Visceral-Medicine-Congress.html [8] Aurigene Oncology Limited Announces Promising Results of Phase 1 Study for India’s First Trial for Novel Autologous CAR-T Cell Therapy for Multiple Myeloma. Retrieved October 11, 2024, from https://www.businesswire.com/news/home/20241008755325/en/Aurigene-Oncology-Limited-Announces-Promising-Results-of-Phase-1-Study-for-India%E2%80%99s-First-Trial-for-Novel-Autologous-CAR-T-Cell-Therapy-for-Multiple-Myeloma/ [9] Immatics Announces Updated Phase 1b Clinical Data on ACTengine® IMA203 TCR-T Targeting PRAME in Melanoma Patients and Provides Update on Upcoming SUPRAME Phase 3 Trial. Retrieved October 10, 2024 from https://www.globenewswire.com/news-release/2024/10/10/2961129/0/en/Immatics-Announces-Updated-Phase-1b-Clinical-Data-on-ACTengine-IMA203-TCR-T-Targeting-PRAME-in-Melanoma-Patients-and-Provides-Update-on-Upcoming-SUPRAME-Phase-3-Trial.html [10] BlueRock Therapeutics’ investigational cell therapy bemdaneprocel for Parkinson’s disease shows positive data at 24-months. Retrieved October 11, 2024, from https://www.bayer.com/en/us/cell-therapy-bemdaneprocel [11] Estrella Immunopharma Achieves Complete Response in First Patient Treated with CD19- Redirected ARTEMIS® T-cells. Retrieved October 11, 2024, from https://www.estrellabio.com/news/estrella-immunopharma-achieves-complete-response-in-first-patient-treated-with-cd19--redirected-artemis%C2%AE-t-cells [12] INKmune Demonstrates Excellent Safety and Increased NK-Cell Activity in First Dosing Cohort. Retrieved October 11, 2024, from https://inmunebio.com/index.php/newsroom/2024-news/muneemonstratesxcellentafetyandncreasede20240926050502 [13] Theriva Biologics Announces Positive Outcome of Data and Safety Monitoring Committee (DSMC) Review in Phase 1b/2a Clinical Trial of SYN-004 (ribaxamase) in Allogeneic Hematopoietic Cell Transplant Recipients. Retrieved October 11, 2024, from https://www.globenewswire.com/news-release/2024/10/03/2957647/0/en/Theriva-Biologics-Announces-Positive-Outcome-of-Data-and-Safety-Monitoring-Committee-DSMC-Review-in-Phase-1b-2a-Clinical-Trial-of-SYN-004-ribaxamase-in-Allogeneic-Hematopoietic-Cel.html [14] Alentis Therapeutics Receives FDA IND Clearance for ALE.P02, a Novel CLDN1-ADC for the Treatment of Squamous Cancers. Retrieved October 11, 2024, from https://pipelinereview.com/alentis-therapeutics-receives-fda-ind-clearance-for-ale-p02-a-novel-cldn1-adc-for-the-treatment-of-squamous-cancers/ [15] NeuroBo Pharmaceuticals Announces Positive Top-Line Data From the SAD Part 1 of Its Phase 1 Clinical Trial Evaluating DA-1726 for the Treatment of Obesity. Retrieved October 11, 2024, from https://www.prnewswire.com/news-releases/neurobo-pharmaceuticals-announces-positive-top-line-data-from-the-sad-part-1-of-its-phase-1-clinical-trial-evaluating-da-1726-for-the-treatment-of-obesity-302261698.html [16] Calidi Biotherapeutics Announces FDA Clearance of the Northwestern University IND Application for CLD-101 Clinical Trial in High-Grade Glioma. Retrieved October 11, 2024, from https://www.globenewswire.com/news-release/2024/09/30/2955149/0/en/Calidi-Biotherapeutics-Announces-FDA-Clearance-of-the-Northwestern-University-IND-Application-for-CLD-101-Clinical-Trial-in-High-Grade-Glioma.html [17] Adcendo Announces US FDA Clearance of IND Application for Phase I/II First-in-Human ADCElerate-01 Trial of ADCE-D01 (uPARAP Receptor Targeting ADC) Trial in Patients With Metastatic and/or Unresectable Soft Tissue Sarcoma (STS). Retrieved October 11, 2024, from https://pipelinereview.com/adcendo-announces-us-fda-clearance-of-ind-application-for-phase-i-ii-first-in-human-adcelerate-01-trial-of-adce-d01-uparap-receptor-targeting-adc-trial-in-patients-with-metastatic-and-or-unresectabl/ [18] Safety and immunogenicity of CD40.HIVRI.Env, a dendritic cell-based HIV vaccine, in healthy HIV-uninfected adults: a first-in-human randomized, placebo-controlled, dose-escalation study (ANRS VRI06). Retrieved October 11, 2024, from https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(24)00424-3/fulltext [19] Myrtelle Announces Significant Reduction in N-Acetylaspartate (NAA), a Key Biomarker, in Patients Treated in Its Phase 1/2 Clinical Trial of the Investigational Gene Therapy rAAV-Olig001-ASPA for Canavan Disease. Retrieved October 11, 2024, from https://www.prnewswire.com/news-releases/myrtelle-announces-significant-reduction-in-n-acetylaspartate-naa-a-key-biomarker-in-patients-treated-in-its-phase-12-clinical-trial-of-the-investigational-gene-therapy-raav-olig001-aspa-for-canavan-disease-302263264.html [20] Kiromic BioPharma Reports Favorable 10-Month Follow-Up Results for the First Patient Treated in its Deltacel-01 Clinical Trial. Retrieved October 11, 2024, from https://www.businesswire.com/news/home/20241001186898/en/Kiromic-BioPharma-Reports-Favorable-10-Month-Follow-Up-Results-for-the-First-Patient-Treated-in-its-Deltacel-01-Clinical-Trial [21] Recursion Announces FDA Clearance of Investigational New Drug Application for REC-1245, a Potential First-In-Class RBM39 Degrader for Biomarker-Enriched Solid Tumors and Lymphoma. Retrieved October 11, 2024, from https://www.globenewswire.com/news-release/2024/10/02/2956875/0/en/Recursion-Announces-FDA-Clearance-of-Investigational-New-Drug-Application-for-REC-1245-a-Potential-First-In-Class-RBM39-Degrader-for-Biomarker-Enriched-Solid-Tumors-and-Lymphoma.html [22] Kymera Therapeutics Announces FDA Clearance of Investigational New Drug Application for KT-621, a First-in-Class, Oral STAT6 Degrader. Retrieved October 11, 2024, from https://investors.kymeratx.com/news-releases/news-release-details/kymera-therapeutics-announces-fda-clearance-investigational-0 [23] Vanqua Bio Announces Positive Interim Results from Phase 1 Clinical Trial of VQ-101, an Orally Administered, Brain-Penetrant, Allosteric Activator of GCase for the Treatment of GBA-Parkinson’s and Related Disorders. Retrieved October 11, 2024, from https://www.globenewswire.com/news-release/2024/10/09/2960411/0/en/Vanqua-Bio-Announces-Positive-Interim-Results-from-Phase-1-Clinical-Trial-of-VQ-101-an-Orally-Administered-Brain-Penetrant-Allosteric-Activator-of-GCase-for-the-Treatment-of-GBA-Pa.html [24] Traws Pharma Announces Positive Topline Phase 1 Data for Flu Candidate, Tivoxavir Marboxil. Retrieved October 11, 2024, from https://www.globenewswire.com/news-release/2024/10/08/2959584/0/en/Traws-Pharma-Announces-Positive-Topline-Phase-1-Data-for-Flu-Candidate-Tivoxavir-Marboxil.html [25] Gain Therapeutics Presents Phase 1 GT-02287 Data at International Congress of Parkinson’s Disease and Movement Disorders Demonstrating Increase in GCase Activity in Healthy Volunteers. Retrieved October 11, 2024, from https://www.globenewswire.com/news-release/2024/09/30/2955049/0/en/Gain-Therapeutics-Presents-Phase-1-GT-02287-Data-at-International-Congress-of-Parkinson-s-Disease-and-Movement-Disorders-Demonstrating-Increase-in-GCase-Activity-in-Healthy-Volunte.html [26] Kura Oncology Announces Publication of Ziftomenib Phase 1 Results in The Lancet Oncology. Retrieved October 11, 2024, from https://www.globenewswire.com/news-release/2024/09/30/2955703/35186/en/Kura-Oncology-Announces-Publication-of-Ziftomenib-Phase-1-Results-in-The-Lancet-Oncology.html [27] Allakos Announces Phase 1 Trial Results of Subcutaneous AK006 in Healthy Volunteers. Retrieved October 11, 2024, from https://investor.allakos.com/news-releases/news-release-details/allakos-announces-phase-1-trial-results-subcutaneous-ak006 [28] Ultragenyx Provides Update on Stage 1 Cohorts in Pivotal Phase 1/2/3 Cyprus2+ Study Evaluating UX701 Gene Therapy for the Treatment of Wilson Disease. Retrieved October 4, 2024, from https://www.globenewswire.com/news-release/2024/10/03/2958032/0/en/Ultragenyx-Provides-Update-on-Stage-1-Cohorts-in-Pivotal-Phase-1-2-3-Cyprus2-Study-Evaluating-UX701-Gene-Therapy-for-the-Treatment-of-Wilson-Disease.html 免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新

细胞疗法临床结果免疫疗法疫苗临床1期

2024-10-09

·GlobeNewswire-Health Care

Panavance Therapeutics Provides Update on Phase 1 Clinical Trial of Misetionamide in Pancreatic Cancer at 2024 Visceral Medicine Congress

Misetionamide-gemcitabine combination demonstrates very good safety profile and potential therapeutic benefit in the challenging treatment of pancreatic adenocarcinoma Interim results show ~40% of patients achieved either a partial response or stable disease Ongoing Phase 1 dose-selection study with final results expected in 2025 BERWYN, PA, Oct. 09, 2024 (GLOBE NEWSWIRE) -- Panavance Therapeutics Inc. (“Panavance” or the “Company”), a clinical-stage pharmaceutical company advancing the development of a novel oncology therapeutic intended to improve the outcomes and quality of life for patients, today announced the presentation of interim data from its Phase 1 clinical study evaluating misetionamide (GP-2250) in combination with gemcitabine at the 2024 Visceral Medicine Congress in Leipzig, Germany. This open label, single arm, multicenter Phase 1 dose escalation clinical trial is enrolling patients with advanced unresectable or metastatic pancreatic ductal adenocarcinoma (PDAC) as a second line therapy for patients who have previously received a first line 5FU containing regimen (e.g. FOLFIRINOX/NALIRIFOX). The study is underway, and this interim data presented includes 49 patients across 11 cohorts. Goals are to establish safety, tolerability, and preliminary efficacy. The safety profile to date has shown zero grade ≥3 adverse events in an initial monotherapy treatment. During the combination therapy with gemcitabine, a total of 5 grade 3 events, and a total of 10 grade 4 events have been observed with all definitely attributed to gemcitabine, and one possibly attributed to misetionamide. The progression free survival of patients treated with the misetionamide-gemcitabine combination compares favorably to historical comparison to gemcitabine alone. There have been 6 partial responders (>30% tumor reduction) thus far including one partial response patient who remained on study 24 months. Anup Kasi, MD, MPH, Associate Professor, Medical Oncology, University of Kansas Cancer Center and primary investigator for the ongoing Phase 1 clinical trial, presented an update at the conference on the clinical trial data to date. “Based on the synergistic effects of misetionamide in combination with gemcitabine, with approximately 40% of patients achieving either a partial response or stable disease, and the degree of tumor regression by this drug combination, compares favorably to historical results with gemcitabine alone. Data from this interim update of the ongoing trial, including initial efficacy together with a very acceptable safety and tolerability profile, support the promise of the misetionamide-gemcitabine combination as a potential new option for the treatment of pancreatic cancer patients,” said Dr. Kasi. “We are pleased to share, for the first time, an interim look at the data from our ongoing Phase 1 dose escalation study. The trial is now at cohorts where the dose levels are in the range (on a mg/kg basis) where effectiveness was observed in the preclinical models. We continue to focus on completing the Phase 1 study with 4 US clinical trial sites and look forward to providing further clinical data updates in 2025,” said Greg Bosch, Chairman and CEO. About Panavance TherapeuticsPanavance Therapeutics Inc. is a privately held, clinical-stage pharmaceutical company developing a novel oncology asset, misetionamide (GP-2250). Panavance was formed in 2021 as a US-based, wholly owned carve out of Geistlich group, a family-owned Swiss company, to focus on misetionamide and the oncology business. Misetionamide is a broadly active small molecule with a unique mechanism of action that inhibits two oncogenic transcription factors, c-MYC and NFκB. Acting through c-MYC, misetionamide selectively disrupts the energy metabolism of cancer cells leading to cancer cell death. Through NFκB inhibition, misetionamide inhibits cancer cells’ ability to proliferate and survive. This mechanism makes misetionamide an attractive tumor cell selective agent. The Company plans to initiate a clinical trial of misetionamide for the treatment of platinum-resistant ovarian cancer and a clinical trial as a first-line maintenance therapy for non-BRCA mutated pancreatic cancer patients. Extensive preclinical studies have demonstrated that misetionamide’s broadly anti-neoplastic MOA has the potential to be effective in additional tumor types, including melanoma, squamous cell, breast, and colorectal cancers. For more information, please visit panavance.com and connect with the Company on Twitter, LinkedIn, and Facebook. Corporate and Investor Relations Contact Lisa DeScenzaLaVoieHealthScience(978)-395-5970ldescenza@lavoiehealthscience.com Media ContactEla WangLaVoieHealthScience(617)-582-3091ewang@lavoiehealthscience.com

临床1期临床结果

2024-08-14

·GlobeNewswire-Health Care

Panavance Therapeutics Announces Foundational Publication of Misetionamide (GP-2250) in Ovarian Cancer in the Journal, Cancer Medicine

Misetionamide demonstrated significant single agent activity and synergy with either PARP inhibitors (PARPi) or bevacizumab in ovarian cancer preclinical studiesProfound effects on tumor metabolism, anti-angiogenic activity, protein synthesis, and DNA transcription BERWYN, PA, Aug. 14, 2024 (GLOBE NEWSWIRE) -- Panavance Therapeutics Inc. (“Panavance” or the “Company”), a clinical-stage pharmaceutical company advancing the development of a novel oncology therapeutic intended to improve the outcomes and quality of life for patients, today announced publication of positive data in the peer-reviewed journal, Cancer Medicine, in a manuscript titled “Mechanism and Rational Combinations with GP-2250, a Novel Oxathiazine Derivative, in Ovarian Cancer.”1 The publication by Kim, et al. (2024) at MD Anderson Cancer Center reports the research on misetionamide which demonstrated excellent monotherapy results as well as synergistic activity with PARPi’s and bevacizumab antineoplastic in ovarian cancer. Misetionamide is a tumor cell selective small molecule drug that is broadly active in multiple cancer models. Misetionamide’s inhibition of hexokinase-2 (HK-2), glyceraldehyde 3-phosphate dehydrogenase (GAPDH), and pyruvate dehydrogenase (PVD) in aerobic glycolysis greatly inhibits ATP production for cancer cells, setting up oxidative, metabolic and hypoxic stresses within the cancer cell. Additionally, misetionamide’s inhibition of key transcription factors such as NFkB further impairs the ability of the cancer cell to express genes and thus sustain viability and proliferation.2 “The key findings in our research are that misetionamide exerts a profound antitumor effect when used as monotherapy as well as synergistically when used either in combination with PARP inhibitors or bevacizumab. Misetionamide also has anti-angiogenic activity that interacts synergistically with bevacizumab. Both findings, and others, strongly suggest that misetionamide in combination with PARPi or bevacizumab should be studied further as a new antitumor drug in ovarian cancers,” said Anil Sood, MD, Department of Gynecologic Oncology and Reproductive Medicine at The University of Texas MD Anderson Cancer Center. “This research demonstrates that misetionamide exerts major anti-cancer effects through new metabolic and transcription inhibition mechanisms. As such, misetionamide may be a promising new therapeutic approach for ovarian cancer patients, which is the fifth leading cause of female cancer death,” commented study author, Robert L. Coleman, MD, Gynecologic Oncologist, Texas Oncology. “The results of this study support our strategy to initiate a clinical trial in ovarian cancer. The Company had a pre-IND meeting with the FDA to discuss our ovarian cancer clinical and regulatory plan in May, and we plan to pursue a Phase 1/2 proof of concept study in platinum-resistant ovarian cancer. Given the high unmet need with approximately 20,000 new cases of ovarian cancer diagnosed each year in the US alone, we are dedicated to bringing new treatment options to these patients,” said Greg Bosch, Chairman and CEO. About Panavance Therapeutics Panavance Therapeutics Inc. is a privately held, clinical-stage pharmaceutical company developing a novel oncology asset, misetionamide (GP-2250). Panavance was formed in 2021 as a US-based, wholly-owned carve out of Geistlich group, a family owned Swiss company, to focus on GP-2250 and the oncology business. Misetionamide is a tumor cell selective and broadly active small molecule with a unique dual mechanism of action of selectively disrupting the energy metabolism of cancer cells leading to cancer cell death as well as impacting nuclear factor-κB (“NFκB”) which affects cancer cells’ ability for protein synthesis and DNA transcription thereby restricting cancer cell growth and proliferation. The Company plans to initiate two clinical studies: a Phase 1/2 study of misetionamide for the treatment of platinum-resistant ovarian cancer and a clinical trial as a first-line maintenance therapy for non-BRCA mutated pancreatic cancer patients. Extensive preclinical studies have demonstrated that misetionamide’s broadly anti-neoplastic MOA has the potential to be effective in additional tumor types, including melanoma, squamous cell, breast, and colorectal cancers. For more information, please visit panavance.com and connect with the Company on Twitter, LinkedIn, and Facebook. Corporate and Investor Relations Contact Lisa DeScenzaLaVoieHealthScience(978) 395-5970ldescenza@lavoiehealthsceince.com Media ContactEla WangLaVoieHealthScience(617)-582-3091 ewang@lavoiehealthscience.com________________________________________ 1Kim MS, Glassman D, Handley KF, Lankenau Ahumada A, Jennings NB, Bayraktar E, Foster K, Joseph R, Lee S, Coleman RL, Sood AK. Mechanism and rational combinations with GP-2250, a novel oxathiazine derivative, in ovarian cancer. Cancer Med. 2024 Aug;13(15):e70031. doi: 10.1002/cam4.70031. PMID: 39114948; PMCID: PMC11306972. 2Majchrzak-Stiller, B.; Buchholz, M.; Peters, I.; Waschestjuk, D.; Strotmann, J.; Höhn, P.; Hahn, S.; Braumann, C.; Uhl, W.; Müller, T.; et al. GP-2250, a novel anticancer agent, inhibits the energy metabolism, activates AMP-Kinase and impairs the NF-kB pathway in pancreatic cancer cells. J. Cell. Mol. Med. 2023, 27, 2082–2092.

100 项与 Misetionamide 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
胰腺癌	临床2期	-	Geistlich Pharma AG	-
转移性胰腺腺癌	临床1期	美国	Geistlich Pharma AG	2019-01-14
成人胰腺癌	临床1期	美国	Geistlich Pharma AG	2019-01-14
乳腺癌	临床前	美国	Panavance Therapeutics, Inc.初创企业	2024-04-22
结直肠癌	临床前	美国	Panavance Therapeutics, Inc.初创企业	2023-11-21
黑色素瘤	临床前	美国	Panavance Therapeutics, Inc.初创企业	2023-11-21
鳞状细胞癌	临床前	美国	Panavance Therapeutics, Inc.初创企业	2023-11-21
卵巢癌	临床前	美国	Panavance Therapeutics, Inc.初创企业	2023-04-17

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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


NCT03854110 (GlobeNewswire) 人工标引	临床1期	胰腺癌二线	49	Misetionamide-gemcitabine	(艱構襯網顧艱夢構願憲) = 繭艱製廠遞蓋簾淵壓壓觸鹹淵鹽餘蓋艱壓齋觸 (鹽鏇衊選構憲顧齋鑰鑰 )	积极	2024-10-09