A First-in-human, Multicenter, Open-label, Dose Escalation and Dose Expansion Phase 1 Study in Patients With Advanced Solid Tumors to Evaluate the Safety of Intravenously Administered ALG.APV-527

A first-in-human, multicenter, open-label, dose escalation and dose expansion phase 1 study in patients with advanced solid tumors to evaluate the safety of intravenously administered ALG.APV-527 (Short title: ALG.APV-527 first-in-human study). Adult patients with advanced/metastatic solid tumors likely to express 5T4 antigen who have failed standard of care regimens for their cancer, have become refractory to standard treatment, or for whom no effective therapy exists based on investigator judgment may be enrolled in this study.
Part 1 (Dose Escalation): Approximately 36 evaluable patients planned to be enrolled.
Part 2 (Dose Expansion): Approximately 20 evaluable patients planned to be enrolled.

开始日期2022-12-23

申办/合作机构

Aptevo Therapeutics, Inc.

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100 项与 ALG.APV-527 相关的临床结果

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100 项与 ALG.APV-527 相关的转化医学

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100 项与 ALG.APV-527 相关的专利（医药）

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项与 ALG.APV-527 相关的新闻（医药）

2024-11-17

·药明康德

12个月患者总生存率超90%的抗癌联合疗法；治疗慢性HBV感染的表观遗传沉默剂进入临床…… | 一周盘点

▎药明康德内容团队编辑本期看点 1. Cue Biopharma公司公布了其两款新型生物制品的积极临床数据，其中接受CUE-101联用PD-1抑制剂pembrolizumab一线治疗的HPV阳性复发性/转移性头颈部鳞状细胞癌（R/M HNSCC）患者12个月时的总生存率为91.3%。 2. 胸苷酸合成酶抑制剂NUC-3373联用pembrolizumab在一项临床研究中使1名尿路上皮膀胱癌患者的靶病灶缩小了100%。 3. 用于治疗慢性乙肝病毒（HBV）感染的表观遗传沉默剂TUNE-401在新西兰获批进入1b期临床试验。药明康德内容团队整理 CUE-101、CUE-102：公布1期临床试验的新数据 Cue Biopharma公司公布其CUE-101治疗头颈癌和CUE-102治疗WT1阳性癌症的1期临床试验的积极新数据。CUE-101是该公司开发的一款基于白细胞介素-2（IL-2）的T细胞诱导剂，旨在选择性调节和激活HPV阳性T细胞，以提高疗效，同时减少传统免疫疗法的副作用。CUE-102是一种由两个呈递WT1肽的人白细胞抗原（HLA）分子、四个亲和力减弱的IL-2分子和一个效应减弱的人免疫球蛋白G（IgG1）Fc结构域组成的新型生物制品，被开发作为单一疗法治疗WT1阳性复发/转移性癌症患者。截至2024年9月11日的数据，接受CUE-101联用PD-1抑制剂pembrolizumab一线治疗的HPV阳性R/M HNSCC患者的客观缓解率（ORR）为46%，疾病控制率（DCR）为75%，12个月时的总生存率为91.3%，中位总生存期（OS）为21.8个月。在历史研究KEYNOTE-048中，pembrolizumab单药治疗的ORR为19%，12个月时的总生存率为51%，中位OS为12.3个月。在本研究中，1例患者达到完全缓解（CR），10例患者达到部分缓解（PR），以及7例患者获得了超过12周的持久疾病稳定（SD）。接受该一线联合治疗的PD-L1低表达患者的ORR为50%。截至2024年10月29日的数据，接受CUE-102单药治疗的晚期胰腺癌患者的DCR为67%，其中包括肿瘤负荷减少40%的未确认的PR。有证据表明，WT1特异性CD8阳性T细胞受到了选择性刺激和扩增，而非特异性CD8阳性T细胞的总数没有明显增加。 NUC-3373：公布1b/2期联合治疗临床试验数据 NuCana公司公布了其正在进行的1b/2期模块化研究的初步数据，模块1研究评估了NUC-3373联用PD-1抑制剂pembrolizumab治疗晚期实体瘤患者的疗效，模块2研究评估了NUC-3373联用多西他赛治疗肺癌患者的疗效。NUC-3373是一种胸苷酸合成酶抑制剂，由核苷类似物5-氟尿嘧啶衍生而来，可导致DNA损伤。模块1包括12名患有各种实体瘤、已用尽所有其他治疗方案的患者，其中9例患者曾接受过PD-1/PD-L1抑制剂的治疗。接受NUC-3373联用pembrolizumab治疗后，患者实现了显著的肿瘤体积缩小，PFS得到延长。2名患者获得了确认的PR，4例患者达到SD。在疗效可评估人群中，ORR为22%，DCR为67%。其中，1例尿路上皮膀胱癌患者接受联合治疗后靶病灶缩小了100%（非靶病灶依然存在），1例BRAF突变转移性皮肤黑色素瘤患者的靶病灶缩小了81%。此外，NUC-3373联合pembrolizumab的耐受性普遍良好。模块2包括4名非小细胞肺癌（NSCLC）或胸膜间皮瘤患者，这些患者在既往含化疗方案中出现疾病进展或无法耐受。患者在接受NUC-3373联用多西他赛治疗后PFS得到延长，2例患者实现了长期的SD。 TUNE-401：在新西兰获批启动1b期临床试验 Tune Therapeutics公司宣布，该公司已获得新西兰药品和医疗器械安全局（Medsafe）的临床试验申请（CTA）批准，将推进其用于治疗慢性HBV感染的表观遗传沉默剂TUNE-401进入1b期临床试验。 TUNE-401是一款潜在"first-in-class"的表观遗传沉默剂，利用Tune Therapeutics的多功能、模块化TEMPO平台所开发。TUNE-401通过脂质纳米颗粒（LNP）将编码活性、HBV靶向的RNA直接递送至肝细胞。在这些细胞内，所递送的RNA被翻译为表观沉默蛋白，靶向整合入宿主细胞的乙肝病毒DNA（intDNA）和共价闭合环状DNA（cccDNA）。cccDNA是一种独特、游离的环状染色体（episomes），可作为病毒进行复制时的模板，是造成HBV患者多年持续感染的原因之一。临床医生认为，关闭这些cccDNA“病毒工厂”是实现HBV功能性治愈的必要前提。TUNE-401不涉及切割或编辑DNA，其导致产生的活性表观沉默蛋白通过添加甲基基团与DNA结合，以抑制或失活病毒基因，同时保持人类基因的完整性。根据新闻稿，TUNE-401是首个获批进入临床，用以治疗常见传染病的表观遗传疗法。 KVA12123：公布1/2期临床试验数据 Kineta公司公布了其正在进行的1/2期临床试验的最新进展，该试验评估了其新型在研VISTA阻断免疫疗法KVA12123单药或与PD-1抑制剂pembrolizumab联用在晚期实体瘤患者中的治疗效果。KVA12123是一种单克隆抗体疗法，需每周输注两次。通过将独特的表位与优化的IgG1 Fc区相结合，KVA12123单药在临床前模型中显示出强大的肿瘤生长抑制作用，且在临床试验中没有报告细胞因子释放综合征（CRS）。KVA12123已被证明能降低VISTA靶点的风险，并提供了一种新的方法来解决肿瘤微环境中的免疫抑制问题，其作用机制与以T细胞为重点的疗法不同且互补。截至2024年10月18日的数据，接受KVA12123单药治疗并至少进行了一次随访扫描的19例患者中，有13名实现了SD。在许多接受KVA12123单药治疗的患者中观察到持久的临床结果，其中1名此前已接受过六线治疗（包括免疫检查点抑制剂治疗）的NSCLC患者已保持SD状态60周。在接受KVA12123联合pembrolizumab治疗并至少进行了一次随访扫描的9例患者中，1例粘液表皮样癌患者获得了PR，靶病灶缩小了54%，非靶病灶获得了CR；1名免疫检查点抑制剂治疗后进展的肾细胞癌患者达到SD，靶病灶缩小了24%。安全性方面，KVA12123的耐受性良好，单药或与pembrolizumab联用在任何剂量水平上都未出现剂量限制性毒性（DLT）。 IDRX-42：公布1/1b期临床试验的新数据 IDRx公司公布了其用于治疗晚期胃肠道间质瘤（GIST）的在研口服小分子KIT酪氨酸激酶抑制剂IDRX-42的1/1b期临床试验数据。IDRX-42旨在选择性地靶向最常见的KIT突变形式，这些突变要么驱动肿瘤细胞的初始生长、增殖和生存，要么使肿瘤对现有疗法产生耐药性。截至2024年9月30日的数据，87例中位治疗线数为四线、疗效可评估患者的ORR为29%，包括1例CR和24例PR。接受IDRX-42作为二线治疗患者的ORR为53%（8/15），包括1例CR和7例PR，这些患者的中位PFS尚未达到。接受IDRX-42作为三线治疗的患者的中位PFS估计为12.9个月。既往未使用过ripretinib、接受IDRX-42作为≥四线治疗的患者在推荐的1b期剂量下，其中位PFS估计为11.0个月。此外，IDRX-42具有良好的安全性，在推荐的1b期剂量下，8%的患者减少了剂量，没有因治疗伴发不良事件而停药的情况。 APV-527：公布1期临床试验数据 Alligator Bioscience公司和Aptevo Therapeutics公司公布了APV-527用于治疗可能表达肿瘤抗原5T4实体瘤患者的1期临床试验数据。APV-527是一种靶向4-1BB和肿瘤抗原5T4的双特异性抗体，仅在与4-1BB和5T4同时结合时才有活性。此次公布的结果显示，16例疗效可评估的患者中有9例（56%）达到SD，其中，1例结肠癌患者已保持SD超过6个月。最长的SD持续时间发生在一名乳腺癌患者中，该患者进入研究时病情发生进展，目前病情保持稳定，且已参与研究超过11个月。安全性方面，APV-527在所有队列中均表现出积极的安全性和耐受性，尚未观察到严重的肝毒性。肝毒性是其他4-1BB靶向治疗的常见副作用，可导致患者停药。 ELI-002：公布1期临床试验的初步数据 Elicio Therapeutics公司公布了其在研治疗性癌症免疫疗法ELI-002用于治疗接受标准局部治疗后仍有疾病复发风险的KRAS突变驱动实体瘤的1期临床试验的初步结果。ELI-002由AMP修饰的KRAS突变体（mKRAS）肽段，和一种AMP修饰的免疫刺激寡核苷酸佐剂ELI-004组成，经皮下给药靶向淋巴结。它能产生RAS特异性杀伤性T细胞，以攻击术后残留肿瘤细胞，有望延长癌症患者缓解并可预防未来复发。初步数据表明，靶向KRAS突变体的T细胞反应持久且呈剂量依赖性，并诱导了针对患者特异性新抗原的反应。观察到无病生存期（DFS）与T细胞反应强度之间存在相关性。此外，ELI-002的1期安全性及耐受性特征依然良好，未观察到DLT或CRS。 GUBamy：公布1期临床试验数据 Gubra公司公布了长效胰淀素（amylin）类似物GUBamy在单剂量递增（SAD）1期临床试验中获得的积极结果。GUBamy耐受性良好，表现出良好的药代动力学特征，半衰期为11天，支持每周一次的给药方案。此外，单剂量的GUBamy剂量依赖性地降低体重，这一效果在试验期间（6周）内持续存在。在所有高剂量组（3.5-6.0 mg）中，受试者在6周试验期内的平均体重下降约3％，而安慰剂组的体重平均增长约1％。 ▲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] Tune Therapeutics Moves into Clinical Spotlight with TUNE-401: A First-in-Class Epigenetic Silencer for Hepatitis B. 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Retrieved November 15, 2024, from https://www.prnewswire.com/news-releases/nammi-therapeutics-inc-announces-first-patient-dosed-with-qxl138am-in-a-phase-1-study-evaluating-advanced-solid-tumors-and-multiple-myeloma-302299498.html [20] Palleon Pharmaceuticals Presents Results from the Phase 1/2 GLIMMER-01 Trial of E-602 in Combination with Cemiplimab in Patients with Solid Tumors at the Society for Immunotherapy of Cancer (SITC) Annual Meeting. Retrieved November 15, 2024, from https://www.businesswire.com/news/home/20241108273263/en/Palleon-Pharmaceuticals-Presents-Results-from-the-Phase-12-GLIMMER-01-Trial-of-E-602-in-Combination-with-Cemiplimab-in-Patients-with-Solid-Tumors-at-the-Society-for-Immunotherapy-of-Cancer-SITC-Annual-Meeting/ [21] Cerevance’s CVN293 Demonstrated Positive Phase 1 Results in Healthy Volunteers. Retrieved November 15, 2024, from https://www.globenewswire.com/news-release/2024/11/11/2978299/0/en/Cerevance-s-CVN293-Demonstrated-Positive-Phase-1-Results-in-Healthy-Volunteers.html [22] Cytokinetics Announces Initiation of Phase 1 Clinical Study of CK-4015089. Retrieved November 15, 2024, from https://ir.cytokinetics.com/news-releases/news-release-details/cytokinetics-announces-initiation-phase-1-clinical-study-ck-2#:~:text=SOUTH%20SAN%20FRANCISCO%2C%20Calif.%2C%20Nov.%2011%2C%202024%20%28GLOBE,study%20of%20CK-4015089%20%28CK-089%29%20in%20healthy%20human%20participants. [23] EnteroBiotix Announces Positive Ph1b Clinical Results of EBX-102 in Liver Cirrhosis. Retrieved November 15, 2024, from https://www.enterobiotix.com/news/enterobiotix-positive-clinical-results-ebx-102-liver-cirrhosis [24] GenVivo to Present Phase 1 Trial Results for GEN2, A Personalizing Gene Vector Therapy, at the 2024 Society for Immunotherapy of Cancer (SITC) Annual Meeting. Retrieved November 15, 2024, from https://genvivoinc.com/2024/11/08/genvivo-to-present-phase-1-trial-results-for-gen2-a-personalizing-gene-vector-therapy-at-the-2024-society-for-immunotherapy-of-cancer-sitc-annual-meeting/ [25] Sparian Biosciences Announces Results from the Phase 1 Clinical Trial of First in Class Novel Arylepoxamide Receptor (AEAr) Agonist Analgesic SBS-1000. Retrieved November 15, 2024, from https://www.globenewswire.com/news-release/2024/11/12/2979419/0/en/Sparian-Biosciences-Announces-Results-from-the-Phase-1-Clinical-Trial-of-First-in-Class-Novel-Arylepoxamide-Receptor-AEAr-Agonist-Analgesic-SBS-1000.html [26] Spyre Therapeutics Announces Positive Interim Results from Phase 1 Healthy Volunteer Trial for SPY001, Its Novel Half-Life Extended anti-α4β7 Antibody for the Treatment of Inflammatory Bowel Disease, with a Half-Life of >90 Days Supporting the Potential for Both Q3M & Q6M Maintenance Dosing. Retrieved November 15, 2024, from https://www.prnewswire.com/news-releases/spyre-therapeutics-announces-positive-interim-results-from-phase-1-healthy-volunteer-trial-for-spy001-its-novel-half-life-extended-anti-47-antibody-for-the-treatment-of-inflammatory-bowel-disease-with-a-half-life-of-90-days-s-302302014.html [27] Nuvectis Pharma Reports Encouraging NXP800 Interim Data Supporting Ongoing Enrollment in Phase 1b Study in Patients with Platinum-Resistant ARID1a-Mutated Ovarian Cancer. Retrieved November 15, 2024, from https://www.globenewswire.com/news-release/2024/11/14/2981017/0/en/Nuvectis-Pharma-Reports-Encouraging-NXP800-Interim-Data-Supporting-Ongoing-Enrollment-in-Phase-1b-Study-in-Patients-with-Platinum-Resistant-ARID1a-Mutated-Ovarian-Cancer.html [28] Enlivex Announces the Dosing of the First Patient in a Phase I Clinical Trial Evaluating Allocetra in Patients with Psoriatic Arthritis. Retrieved November 15, 2024, from https://enlivex.com/investors/news-releases/enlivex-announces-the-dosing-of-the-first-patient-in-a-phase-i-clinical-trial-evaluating-allocetra-in-patients-with-psoriatic-arthritis/#:~:text=Nes-Ziona%2C%20Israel%2C%20Nov.%2014%2C%202024%20%E2%80%94%20Enlivex%20Therapeutics,an%20affected%20joint%20in%20patients%20with%20psoriatic%20arthritis. 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

临床2期临床结果免疫疗法临床1期

2024-09-22

·药明康德

使88%患者前列腺特异性抗原减少超90%的联合疗法；疾病控制率近90%的ADC疗法…… | 一周盘点

▎药明康德内容团队编辑本期看点 1. 抗体偶联药物（ADC）rinatabart sesutecan（Rina-S）用于治疗表达叶酸受体α（FRα）的晚期卵巢癌患者，在一项早期临床试验中的疾病控制率（DCR）近90%。 2. 第二代抗雄激素药物masofaniten联用恩杂鲁胺（enzalutamide）治疗转移性去势抵抗性前列腺癌（mCRPC）患者的1/2期临床试验结果积极，88%患者的前列腺特异性抗原（PSA）减少≥90%（PSA90）。 3. 抗CD39抗体TTX-030的联合疗法一线治疗转移性胰腺癌，在一项早期临床试验中使3名患者获得完全缓解（CR）。药明康德内容团队整理 Rinatabart Sesutecan（Rina-S）：公布1/2期临床试验数据 Genmab公司公布了其靶向FRα的抗体偶联药物Rina-S的1/2期临床试验数据。Rina-S旨在治疗比第一代FRα靶向ADC更广泛的患者群体。2024年1月，美国FDA授予Rina-S快速通道资格，用于治疗表达FRα的高级别浆液性或子宫内膜样铂耐药卵巢癌患者。该研究的B部分将42名既往接受过治疗的经组织学或细胞学确诊的晚期卵巢癌（上皮性卵巢癌、原发性腹膜癌或输卵管癌）的患者随机分配接受100 mg/m2 Rina-S（n=22）或120 mg/m2 Rina-S（n=20）治疗。接受100 mg/m2 Rina-S治疗患者的确认的客观缓解率（ORR）为18.2%，4名患者获得了部分缓解（PR），15例患者实现疾病稳定（SD），DCR为86.4%。120 mg/m2组患者的ORR为50.0%，1名患者获得CR，4名患者获得了PR，8名患者为SD，DCR为88.9%。基于这些结果，Rina-S 120 mg/m2剂量已被选定在2024年开始的针对晚期卵巢癌患者的3期临床试验中进行进一步评估。安全性方面，该研究中常见的治疗伴发不良事件（TEAE）包括贫血、中性粒细胞减少、恶心、血小板减少、白细胞减少、疲劳、呕吐、脱发和腹泻。剂量减少和治疗中止的情况较少，未观察到眼部毒性、神经病变或间质性肺病（ILD）的信号。 Masofaniten（EPI-7386）：公布1/2期联合治疗临床试验的新数据 ESSA Pharma公司公布了其第二代抗雄激素药物masofaniten与恩杂鲁胺联合治疗转移性去势抵抗性前列腺癌患者的1/2期临床试验的新数据。Masofaniten是一种高选择性的雄激素受体N-末端结构域的口服小分子抑制剂。此次公布的研究结果显示，该组合疗法32个给药周期测试的剂量水平下耐受性良好。无论患者先前的化疗状态如何，包括接受低于全剂量（120 mg）恩杂鲁胺的患者在内，mCRPC患者的PSA都有快速、深度且持久的降低。在所有队列中，88%（14/16）的患者达到了PSA90，69%（11/16）的患者在90天内达到PSA90，63%（10/16）患者达到PSA<0.2 mg/mL的水平。中位随访时间为15.2个月时，PSA进展的中位时间以及影像学无进展生存期尚未达到。 TTX-030：公布1期临床试验数据 Trishula Therapeutics公司公布了其与艾伯维（AbbVie）合作开发的抗CD39抗体TTX-030一线治疗转移性胰腺癌患者的1期临床试验结果。CD39是一种将三磷酸腺苷（ATP）转化为单磷酸腺苷（AMP）的酶，是在肿瘤微环境中生成腺苷的初始步骤。TTX-030能够阻止免疫抑制性胞外腺苷的生成，并维持高水平的免疫激活性胞外ATP，进而刺激树突状细胞和骨髓衍生细胞，促进先天性和适应性抗肿瘤免疫反应。该1期临床试验评估了TTX-030＋吉西他滨/白蛋白结合型紫杉醇联合使用±budigalimab（一种在研PD-1抗体）作为胰腺癌一线治疗的效果。在可评估疗效的人群（n=57）中，92%为一线转移性胰腺癌患者，8%为局部晚期不可切除患者，ORR为30%，其中3名患者获得了CR。中位无进展生存期（PFS）为7.5个月，中位总生存期（OS）为19.1个月。在28名高表达免疫相关生物标志物HLA-DQ的患者中，ORR为46%，中位PFS为9.6个月，中位OS为21.9个月。安全性方面，两种治疗方案的耐受性良好，只有5名患者（8%）因不良事件（AE）中止治疗。最常见的不良事件为标准化疗方案中预期出现的不良反应，未见发生频率或严重程度的增加。 CFT1946：公布1期临床试验数据 C4 Therapeutics公司公布了其小分子降解剂CFT1946治疗携带BRAF V600突变的实体瘤患者的1期临床试验数据。CFT1946可以直接降解突变BRAF蛋白，消除其蛋白支架的功能，从而彻底规避RAF信号的异常激活。在临床前研究中，CFT1946导致BRAF-V600E突变体的降解，显著抑制MAPK信号传导，并且在降低BRAF-V600E细胞生存能力的同时并未影响野生型BRAF细胞。在BRAF V600E小鼠肿瘤模型中，CFT1946也导致肿瘤显著缩小。截至2024年7月19日的数据，27名可评估患者中有16名的靶转移灶缩小，2名患者获得了CR。此外，CFT1946在迄今为止探索的5个剂量水平中表现出剂量依赖性的生物利用度。在迄今为止收集的所有可用的治疗后活检样本中，均观察到BRAF V600E蛋白的降解。安全性方面，CFT1946具有良好的耐受性和安全性，支持其作为单一疗法以及与MEK和EGFR抑制剂联用进行进一步的临床开发。 Brenetafusp（IMC-F106C）：公布1期临床试验数据 Immunocore公司公布了brenetafusp在铂耐药卵巢癌患者中的1期数据。IMC-F106C是一种通过ImmTAX平台开发，靶向PRAME抗原的双特异性蛋白。该研究中，37例既往接受过大量治疗（中位线数为5线）的浆液性卵巢癌患者接受了 brenetafusp单药治疗，大多数患者既往接受过贝伐珠单抗（81%）和PARP抑制剂（59%）。31例可评估患者的DCR为58%，2例患者获得确认的PR。在所有37例患者中，中位PFS为3.3个月，6个月时的总生存率为73%。在可评估循环肿瘤DNA（ctDNA）的29例患者中，31%获得了分子学缓解。 16例既往接受过大量治疗（中位线数为4线）的铂类耐药卵巢癌患者接受了brenetafusp联用化疗的治疗，大多数患者既往接受过贝伐珠单抗（75%）和PARP抑制剂（75%）。Brenetafusp联合化疗的安全性与每种单独药物的预期特征一致。13例可评估患者的DCR为69%，3例患者获得PR。在可评估ctDNA的11例患者中，82%获得了分子学缓解。 IMA401：公布1期临床试验数据 Immatics公司公布了其下一代半衰期延长的T细胞受体（TCR）双特异性抗体平台的首个候选药物IMA401的概念验证临床数据。IMA401靶向HLA-A*02呈递的肽，该肽来源于两种不同的癌症相关蛋白，即黑色素瘤相关抗原4和/或8（MAGEA4/8）。来自首次人体1期剂量递增试验的数据表明，IMA401单药治疗具有初始抗肿瘤活性和可控的耐受性。患者群体包括35名既往接受过大量治疗的患者，共涉及16种不同的实体瘤类型。在MAGEA4/8水平高且接受相关IMA401剂量的患者人群中，ORR为29%，DCR为53%。此外，在头颈部鳞状细胞癌、神经内分泌肿瘤、皮肤和粘膜黑色素瘤患者中观察到客观缓解，包括长达超过13个月的持久PR和深度缓解（肿瘤缩小≥50%）。药代动力学数据表明，IMA401的中位半衰期为16.9天，支持当前的每两周一次的给药方案和未来延长至四周一次的给药方案。 ▲IMA401的概念验证研究数据（图片来源：参考资料[6]） CY-101（CyPep-1）：公布1/2a期临床试验数据 Cytovation公司公布了其双功能免疫疗法CY-101联用抗PD-1疗法帕博利珠单抗治疗晚期实体瘤的1/2a期临床试验结果。CyPep-1是一种独特的、高度差异化的合成肽疗法，它具有独特的双重作用机制，既能通过激活Axin2抑制Wnt/β-catenin致癌通路，还能通过释放新抗原激活全身性肿瘤特异性免疫反应。此次公布的结果显示，在推荐的2期剂量（RP2D）下，CY-101具有良好的耐受性。配对肿瘤活检分析表明，患有不同癌种的患者接受RP2D治疗，癌细胞的死亡率>70%，并转化为临床获益。值得注意的是，在接受CY-101单药治疗的6例肾上腺皮质癌患者中，观察到DCR为50%，2例患者缓解超过6个月。这两名患者均表达β-catenin，且Wnt/β-catenin通路中发生了体细胞突变。 Luveltamab tazevibulin（luvelta）：公布1b期联合治疗临床试验的新数据 Sutro Biopharma公司公布了正在进行的luveltamab tazevibulin（luvelta）联合贝伐珠单抗治疗上皮性卵巢癌患者的1b期研究的最新数据。Luvelta是一种FRα靶向ADC，每个抗体含有4个hemiasterlin细胞毒素，能够精确定位并有效递送至肿瘤，同时确保给药后的全身稳定性。在这项研究中，luvelta联合贝伐珠单抗在晚期卵巢癌患者中显示出令人鼓舞的抗肿瘤活性，无论FRα表达如何（包括没有FRα表达的患者），以及既往接受过贝伐珠单抗治疗的患者，总缓解率为35%，中位缓解持续时间为9.3个月。RP2D组患者的ORR为56%。这些早期数据提示luvelta有望作为一种非生物标志物驱动的方法来治疗上皮性卵巢癌患者。 APV-527：公布1期临床试验数据 Alligator Bioscience公司和Aptevo Therapeutics公司公布了APV-527用于治疗可能表达肿瘤抗原5T4的实体瘤患者的1期临床试验数据。APV-527是一种靶向4-1BB和肿瘤抗原5T4的双特异性抗体，仅在与4-1BB和5T4同时结合时才有活性。此次公布的结果显示，15名疗效可评估的患者中有9名（60%）实现了SD，1名乳腺癌患者已保持SD超过11个月，1名结肠癌患已保持SD超过4个月。安全性方面，APV-527在所有队列中均表现出积极的安全性和耐受性，尚未确定最大耐受剂量。 GV20-0251：公布1期临床试验数据 GV20 Therapeutics公司公布了其靶向新型免疫检查点IGSF8的抗体疗法GV20-0251治疗实体瘤患者的1/2期研究结果。结果显示，29例疗效可评估的患者中有14例获得了SD，包括4例肿瘤缩小。在12例疗效可评估的转移性皮肤黑色素瘤患者中观察到2例确认的PR。安全性方面，GV20-0251在所有剂量水平下均具有良好的耐受性，未观察到剂量限制性毒性。大多数治疗相关不良事件为1/2级，仅报道1例3级肺炎。 ▲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] Investigational Rinatabart Sesutecan (Rina-S) Shows Promising Anti-Tumor Activity as Single Agent in Heavily Pretreated Patients with Ovarian and Endometrial Cancers in Phase 1/2 Clinical Trial. Retrieved September 20, 2024, from https://ir.genmab.com/news-releases/news-release-details/investigational-rinatabart-sesutecan-rina-s-shows-promising-anti [2] ESSA Pharma Presents Updated Phase 1/2 Masofaniten (EPI-7386) Clinical Data at the 2024 ESMO Congress. Retrieved September 20, 2024, from https://www.prnewswire.com/news-releases/essa-pharma-presents-updated-phase-12-masofaniten-epi-7386-clinical-data-at-the-2024-esmo-congress-302248122.html [3] Trishula Therapeutics Presents Positive Results from Phase 1 Trial of TTX-030 in First-Line Metastatic Pancreatic Cancer Patients. Retrieved September 20, 2024, from https://www.prnewswire.com/news-releases/trishula-therapeutics-presents-positive-results-from-phase-1-trial-of-ttx-030-in-first-line-metastatic-pancreatic-cancer-patients-302247474.html [4] C4 Therapeutics Presents Monotherapy Data Demonstrating Proof of Mechanism and Early Evidence of Proof of Concept From Ongoing CFT1946 Phase 1 Trial in BRAF V600 Mutant Solid Tumors at the European Society for Medical Oncology (ESMO) Congress 2024. Retrieved September 20, 2024, from https://www.globenewswire.com/news-release/2024/09/13/2946010/0/en/C4-Therapeutics-Presents-Monotherapy-Data-Demonstrating-Proof-of-Mechanism-and-Early-Evidence-of-Proof-of-Concept-From-Ongoing-CFT1946-Phase-1-Trial-in-BRAF-V600-Mutant-Solid-Tumor.html [5] Immunocore presents Phase 1 data of brenetafusp, an ImmTAC bispecific targeting PRAME, in patients with ovarian cancer. Retrieved September 20, 2024, from https://www.globenewswire.com/news-release/2024/09/14/2946230/0/en/Immunocore-presents-Phase-1-data-of-brenetafusp-an-ImmTAC-bispecific-targeting-PRAME-in-patients-with-ovarian-cancer.html [6] Immatics Presents Clinical Proof-of-Concept Data from Ongoing Phase 1 Dose Escalation Trial with TCR Bispecific Molecule TCER® IMA401 Targeting MAGEA4/8 at ESMO 2024 and Provides Development Update. Retrieved September 20, 2024, from https://investors.immatics.com/news-releases/news-release-details/immatics-presents-clinical-proof-concept-data-ongoing-phase-1-0/ [7] Cytovation to present full safety and efficacy data from the CICILIA Phase I/IIa trial evaluating CY-101 in solid tumors at ESMO 2024. Retrieved September 20, 2024, from https://www.globenewswire.com/news-release/2024/09/13/2945717/0/en/Cytovation-to-present-full-safety-and-efficacy-data-from-the-CICILIA-Phase-I-IIa-trial-evaluating-CY-101-in-solid-tumors-at-ESMO-2024.html#:~:text=Cytovation%20to%20present%20full%20safety%20and%20efficacy%20data,activity%2C%20especially%20in%20tumors%20with%20dysregulated%20Wnt%2F%CE%B2-catenin%20signalling [8] Alligator Bioscience and Aptevo Therapeutics Announce Data from Phase 1 ALG.APV-527 Monotherapy Trial Showing 60% of Evaluable Patients Achieved Stable Disease in Solid Tumor Study. Retrieved September 20, 2024, from https://alligatorbioscience.se/en/mfn_news/alligator-bioscience-and-aptevo-therapeutics-announce-data-from-phase-1-alg-apv-527-monotherapy-trial-showing-60-of-evaluable-patients-achieved-stable-disease-in-solid-tumor-study/ [9] Sutro Biopharma Announces Updated Data from Phase 1b Study of Luvelta in Combination with Bevacizumab at ESMO 2024. Retrieved September 20, 2024, from https://www.globenewswire.com/news-release/2024/09/14/2946228/0/en/Sutro-Biopharma-Announces-Updated-Data-from-Phase-1b-Study-of-Luvelta-in-Combination-with-Bevacizumab-at-ESMO-2024.html [10] GV20 Therapeutics Presents Promising Phase 1 Monotherapy Data on Novel Checkpoint Inhibitor GV20-0251 at ESMO Congress 2024. Retrieved September 20, 2024, from https://www.prnewswire.com/news-releases/gv20-therapeutics-presents-promising-phase-1-monotherapy-data-on-novel-checkpoint-inhibitor-gv20-0251-at-esmo-congress-2024-302247149.html [11] AAVantgarde announces first patient dosed in First-In-Human Phase 1/2 LUCE-1 study, evaluating AAVB-081 (Dual-AAV) in retinitis pigmentosa related to Usher Syndrome type 1B. Retrieved September 20, 2024, from https://www.globenewswire.com/news-release/2024/09/16/2946331/0/en/AAVantgarde-announces-first-patient-dosed-in-First-In-Human-Phase-1-2-LUCE-1-study-evaluating-AAVB-081-Dual-AAV-in-retinitis-pigmentosa-related-to-Usher-Syndrome-type-1B.html [12] Biosyngen's first-in-class CAR-T asset targeting solid tumors has entered pivotal phase II trial, Phase I trial data debut at ESMO 2024 Annual Congress. Retrieved September 20, 2024, from https://www.prnewswire.com/news-releases/biosyngens-first-in-class-car-t-asset-targeting-solid-tumors-has-entered-pivotal-phase-ii-trial-phase-i-trial-data-debut-at-esmo-2024-annual-congress-302251709.html [13] Vico Therapeutics Announces Positive Interim Phase 1/2a Clinical Data of VO659 in Treatment of Huntington's Disease. Retrieved September 20, 2024, from https://www.prnewswire.com/news-releases/vico-therapeutics-announces-positive-interim-phase-12a-clinical-data-of-vo659-in-treatment-of-huntingtons-disease-302247239.html [14] Cybrexa Therapeutics Announces Positive Final Data at ESMO 2024 from Phase 1 Study of Peptide Drug Conjugate CBX-12 in Advanced Solid Tumors. Retrieved September 20, 2024, from https://www.globenewswire.com/news-release/2024/09/16/2946456/0/en/Cybrexa-Therapeutics-Announces-Positive-Final-Data-at-ESMO-2024-from-Phase-1-Study-of-Peptide-Drug-Conjugate-CBX-12-in-Advanced-Solid-Tumors.html [15] Cullinan Therapeutics Announces Submission of Investigational New Drug Application to U.S. Food and Drug Administration for CLN-978 to Treat Systemic Lupus Erythematosus. Retrieved September 20, 2024, from https://www.globenewswire.com/news-release/2024/09/16/2946504/0/en/Cullinan-Therapeutics-Announces-Submission-of-Investigational-New-Drug-Application-to-U-S-Food-and-Drug-Administration-for-CLN-978-to-Treat-Systemic-Lupus-Erythematosus.html [16] TORL BioTherapeutics Presents Updated Phase 1 Results of Novel Claudin 6 Targeted Antibody-Drug Conjugate TORL-1-23 at the 2024 European Society of Medical Oncology Congress. Retrieved September 20, 2024, from https://www.prnewswire.com/news-releases/torl-biotherapeutics-presents-updated-phase-1-results-of-novel-claudin-6-targeted-antibody-drug-conjugate-torl-1-23-at-the-2024-european-society-of-medical-oncology-congress-302248489.html [17] NextCure Presented Results of the Phase 1b Study of NC410 in Combination with Pembrolizumab at ESMO 2024. Retrieved September 20, 2024, from https://www.globenewswire.com/news-release/2024/09/16/2946611/0/en/NextCure-Presented-Results-of-the-Phase-1b-Study-of-NC410-in-Combination-with-Pembrolizumab-at-ESMO-2024.html [18] Sonnet BioTherapeutics Completes Enrollment in Phase 1 Study of SON-1010 (IL12-FHAB) as a Monotherapy (SB101) for the Treatment of Solid Tumors. Retrieved September 20, 2024, from https://www.sonnetbio.com/news-media/press-releases/detail/97/sonnet-biotherapeutics-completes-enrollment-in-phase-1 [19] Engrail Therapeutics Initiates ENX-104 Clinical Program for the Treatment of Major Depressive Disorder Characterized by Anhedonia. Retrieved September 20, 2024, from https://www.globenewswire.com/news-release/2024/09/18/2948077/0/en/Engrail-Therapeutics-Initiates-ENX-104-Clinical-Program-for-the-Treatment-of-Major-Depressive-Disorder-Characterized-by-Anhedonia.html [20] Antennova Releases Latest Data of CD73 Inhibitor ATN-037, including a DCR of 89.5%, in a Mini Oral at ESMO Congress 2024. Retrieved September 20, 2024, from https://www.prnewswire.com/news-releases/antennova-releases-latest-data-of-cd73-inhibitor-atn-037--including-a-dcr-of-89-5-in-a-mini-oral-at-esmo-congress-2024--302247371.html [21] Incyte’s CDK2 Inhibitor INCB123667 Shows Promising Evidence of Clinical Activity in Patients with Advanced Solid Tumors, Notably Ovarian Cancer. Retrieved September 20, 2024, from https://investor.incyte.com/news-releases/news-release-details/incytes-cdk2-inhibitor-incb123667-shows-promising-evidence [22] Eisbach Bio Announces First Patient Dosed in Phase 1/2 Trial for EIS-12656, a First-In-Class Allosteric Inhibitor of ALC1 in Refractory Advanced Solid Tumors. Retrieved September 20, 2024, from https://www.globenewswire.com/news-release/2024/09/16/2946482/0/en/Eisbach-Bio-Announces-First-Patient-Dosed-in-Phase-1-2-Trial-for-EIS-12656-a-First-In-Class-Allosteric-Inhibitor-of-ALC1-in-Refractory-Advanced-Solid-Tumors.html [23] Nxera’s Partner Cancer Research UK to Present on Phase 1/2a Clinical Trial with Cancer Immunotherapy Drug HTL0039732 at ESMO. Retrieved September 20, 2024, from https://www.globenewswire.com/news-release/2024/09/13/2945711/0/en/Nxera-s-Partner-Cancer-Research-UK-to-Present-on-Phase-1-2a-Clinical-Trial-with-Cancer-Immunotherapy-Drug-HTL0039732-at-ESMO.html [24] Scorpion Therapeutics Presents Initial Clinical Data from Its Phase 1/2 Trial of STX-478 Demonstrating Potentially Best-in-Class Mutant-Selective PI3Kα Inhibition for the Treatment of Advanced Solid Tumors at ESMO Congress 2024. Retrieved September 20, 2024, from https://www.scorpiontx.com/press-release/scorpion-therapeutics-presents-initial-clinical-data-from-its-phase-1-2-trial-of-stx-478-demonstrating-potentially-best-in-class-mutant-selective-pi3k%ce%b1-inhibition-for-the-treatment-of-advanced-so/ [25] Satellos Announces Dosing of First Participant in Phase 1 Clinical Study of SAT-3247. Retrieved September 20, 2024, from https://www.businesswire.com/news/home/20240918008946/en/Satellos-Announces-Dosing-of-First-Participant-in-Phase-1-Clinical-Study-of-SAT-3247 [26] Anokion Announces New Data from the Phase 1 MoveS-it Study Supporting ANK-700 as a Novel, Potential Disease Modifying Treatment for Relapsing-Remitting Multiple Sclerosis. Retrieved September 20, 2024, from https://www.businesswire.com/news/home/20240917374019/en/Anokion-Announces-New-Data-from-the-Phase-1-MoveS-it-Study-Supporting-ANK-700-as-a-Novel-Potential-Disease-Modifying-Treatment-for-Relapsing-Remitting-Multiple-Sclerosis [27] Tectonic Therapeutic Announces Favorable Phase 1a Safety, Tolerability and PK/PD Results for Lead Program TX45. Retrieved September 20, 2024, from https://www.globenewswire.com/news-release/2024/09/19/2949404/0/en/Tectonic-Therapeutic-Announces-Favorable-Phase-1a-Safety-Tolerability-and-PK-PD-Results-for-Lead-Program-TX45.html [28] Beacon Therapeutics Presents 36-Month Interim Results from Phase I/2 HORIZON Trial of AGTC-501 in Patients with XLRP. Retrieved September 20, 2024, from https://www.prnewswire.com/news-releases/beacon-therapeutics-presents-36-month-interim-results-from-phase-i2-horizon-trial-of-agtc-501-in-patients-with-xlrp-302252375.html [29] Edgewise Therapeutics Announces Positive Top-Line Data from Phase 1 Trial in Healthy Subjects and Phase 2 CIRRUS-HCM Trial in Patients with Obstructive Hypertrophic Cardiomyopathy (HCM). Retrieved September 20, 2024, from https://www.businesswire.com/news/home/20240919115598/en/Edgewise-Therapeutics-Announces-Positive-Top-Line-Data-from-Phase-1-Trial-in-Healthy-Subjects-and-Phase-2-CIRRUS-HCM-Trial-in-Patients-with-Obstructive-Hypertrophic-Cardiomyopathy-HCM [30] TransCode Therapeutics Announces First Patients Treated in Phase 1 Clinical Trial with First-in-Class Lead Therapeutic Candidate. Retrieved September 20, 2024, from https://www.globenewswire.com/news-release/2024/09/17/2947285/0/en/TransCode-Therapeutics-Announces-First-Patients-Treated-in-Phase-1-Clinical-Trial-with-First-in-Class-Lead-Therapeutic-Candidate.html [31] Prelude Therapeutics’ SMARCA2 Degrader PRT3789 Demonstrated Promising Initial Clinical Activity and Safety Profile in Phase 1 Trial. Retrieved September 20, 2024, from https://investors.preludetx.com/news-releases/news-release-details/prelude-therapeutics-smarca2-degrader-prt3789-demonstrated [32] Botensilimab/Balstilimab Clinical Responses in Refractory Sarcomas Presented at ESMO 2024. Retrieved September 20, 2024, from https://investor.agenusbio.com/news/news-details/2024/BotensilimabBalstilimab-Clinical-Responses-in-Refractory-Sarcomas-Presented-at-ESMO-2024/default.aspx [33] CureVac’s CVGBM Cancer Vaccine Induces Promising Immune Responses in Phase 1 Study in Glioblastoma Presented at the ESMO 2024 Congress. Retrieved September 20, 2024, from https://www.curevac.com/en/curevacs-cvgbm-cancer-vaccine-induces-promising-immune-responses-in-phase-1-study-in-glioblastoma-presented-at-the-esmo-2024-congress/ 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

临床结果快速通道临床2期抗体药物偶联物

2024-09-16

·PipelineReview

Alligator Bioscience and Aptevo Therapeutics Announce Data from Phase 1 ALG.APV-527 Monotherapy Trial Showing 60% of Evaluable Patients Achieved Stable Disease in Solid Tumor Study

LUND, Sweden I September 16, 2024 I Alligator Bioscience AB (“Alligator”) (Nasdaq Stockholm:ATORX) and Aptevo Therapeutics (“Aptevo”) (Nasdaq: APVO) today announced positive interim data from the dose escalation phase of their Phase 1 trial evaluating ALG.APV-527 for the treatment of solid tumors likely to express the tumor antigen 5T4. The results, which include clinical activity, safety, tolerability outcomes, pharmacokinetics and pharmacodynamics were presented in a poster session on Saturday, September 14, 2024, at the European Society for Medical Oncology (ESMO) Annual Congress in Barcelona, Spain. ALG.APV-527 is a first-in-class bispecific antibody that targets 4-1BB and the tumor antigen 5T4. The compound is being evaluated in a multi-center, dose escalation trial that has 18 patients included in the safety analysis. These patients received multiple prior rounds of therapy for the treatment of solid tumor types. The trial is approaching full enrollment and interim results include: Clinical Activity/Efficacy Safety and Tolerability Evidence of favorable pharmacokinetics and biological activity of ALG.APV-527 “4-1BB has been a target of interest-though with excess toxicity-for decades, and novel bispecific approaches like this will enable us to maximize anti-tumor immunity while limiting the systemic toxicity concerns that have plagued this key immune costimulatory receptor. With this backdrop, these Phase 1 interim results are very encouraging, with ALG.APV-527 showing a positive safety profile with 60% of evaluable patients achieving stable disease, meaning not progressing for variable time frames including one breast cancer patient being treated with monotherapy on study with SD for more than 11 months. We are excited to see signs of clinical activity, underscoring the potential of the drug to benefit patients with solid tumors in the clinical setting, supported by a positive safety and tolerability profile,” stated Thomas Marron, MD, PhD, Professor in Immunology & Immunotherapy and in Medicine, Hematology and Medical Oncology at Icahn School of Medicine at Mount Sinai , participating Investigator of the trial. Trial Overview The ALG.APV-527 Phase 1 trial is a multi-center, multi-cohort, open-label dose-escalation trial that includes administration of ALG.APV-527 in up to six escalating dose levels in a 3+3 design*. The trial is enrolling adult patients with multiple solid tumor types/histologies likely to express the 5T4 antigen. ALG.APV-527 will be given intravenously once every two weeks. The trial is assessing the safety and tolerability, pharmacokinetics, pharmacodynamics and preliminary anti-tumor activity of ALG.APV-527. *The 3+3 design proceeds in cohorts of three patients treated at increasing dose levels. Dose escalation stops when at least two out of three or six patients experience dose limiting toxicities (DLTs) at that dose level. About ALG.APV-527 ALG.APV-527 is a bispecific conditional 4-1BB agonist, only active upon simultaneous binding to 4-1BB and 5T4. This has the potential to be clinically important because 4-1BB can stimulate the immune cells (antitumor-specific T cells and NK cells) involved in tumor control, making 4-1BB a particularly compelling target for cancer immunotherapy. 5T4 is an oncofetal tumor associated antigen overexpressed on numerous solid tumors including non-small-cell lung carcinoma (NSCLC), breast, head and neck, cervical, renal, gastric, and colorectal cancer. Preclinical studies, highlighting the differentiated design of the molecule that minimizes systemic immune activation, allowing for highly efficacious tumor-specific responses as demonstrated by potent activity in preclinical models, has been published in the peer-reviewed publication, Molecular Cancer Therapeutics , a journal of the American Association for Cancer Research (AACR). About Alligator Bioscience Alligator Bioscience AB is a clinical-stage biotechnology company developing tumor-directed immuno-oncology antibody drugs. Alligator’s portfolio includes several promising drug candidates, with the CD40 agonist mitazalimab as its key asset. Furthermore, Alligator is co-developing ALG.APV-527 with Aptevo Therapeutics Inc., several undisclosed molecules based on its proprietary technology platform, Neo-X-Prime™, and novel drug candidates based on the RUBY™ bispecific platform with Orion Corporation. Out-licensed programs include AC101/HLX22, in Phase 2 development, by Shanghai Henlius Biotech Inc. and an undisclosed target to Biotheus Inc. Alligator Bioscience’s shares are listed on Nasdaq Stockholm (ATORX) and is headquartered in Lund, Sweden. For more information, please visit alligatorbioscience.com . About Aptevo Therapeutics Aptevo Therapeutics Inc. is a clinical-stage biotechnology company focused on developing novel bispecific immunotherapies for the treatment of cancer. Aptevo is seeking to improve treatment outcomes and transform the lives of cancer patients. For more information, please visit www.aptevotherapeutics.com . SOURCE: Aptevo Therapeutics

临床1期临床结果免疫疗法AACR会议临床2期

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适应症	最高研发状态	国家/地区	公司	日期
晚期恶性实体瘤	临床2期	美国	Aptevo Therapeutics, Inc.	2022-12-23

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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


NCT05934539 (ESMO2024) 人工标引	临床1期	晚期恶性实体瘤	14	ALG.APV-527 0.1-15 mg/kg	(願艱艱網築鬱簾鹽網壓) = A total of 14 patients experienced 73 treatment-related adverse events. Most events were mild to moderate and manageable in the clinic; G1=30 (41%), G2=32, (44%), G3=8 (11%), G4=3 (4%), G5=0. 襯簾襯壓夢餘網艱構鏇 (艱獵積鬱艱繭衊膚願醖 ) 更多	积极	2024-09-14
Biospace 人工标引	临床1期	实体瘤	-	ALG.APV-527	(鬱製構觸壓製蓋鏇鹹簾) = Treatment was overall well-tolerated, and a maximum tolerated dose has not yet been determined, dose-escalation in higher-dose cohorts is ongoing 鏇繭夢鏇蓋蓋遞壓製壓 (餘簾網築積選獵積憲鹹 ) 更多	积极	2024-03-07