The Seena Magowitz Phase IB/II Trial of CMP-001 (a TLR9 Agonist) in Combination With INCAGN01949 (an Activating Anti-OX40 Antibody) for In Situ Intratumoral Injection for Patients With Stage IV Pancreatic and Other Cancers Except Melanoma

This phase Ib/II trial studies the side effects and best dose of CMP-001 and how well it works when given together with INCAGN01949 in treating patients with stage IV pancreatic cancer and other cancers except melanoma. CMP-001 is made up of a short piece of DNA that is packaged in a protein, known as a virus-like particle (VLP). VLPs are detected and processed by cells of the immune system. The DNA contained in CMP-001 activates the immune system and recruit cells of the immune system to the tumor. INCAGN01949 is an antibody, a type of protein, which has been shown to stimulate the immune system. Injecting CMP-001 and INCAGN01949 directly into the tumor may work against tumor cells to slow tumor growth by causing tumor cells to die.

开始日期2021-04-29

申办/合作机构

University of Southern California

[+1]

NCT03241173

/ Completed临床1/2期

A Phase 1/2 Study Exploring the Safety, Tolerability, and Efficacy of INCAGN01949 in Combination With Immune Therapies in Subjects With Advanced or Metastatic Malignancies

The purpose of this study is to determine the safety, tolerability, and efficacy of INCAGN01949 when given in combination with immune therapies in participants with advanced or metastatic malignancies.

开始日期2017-10-09

申办/合作机构

Incyte Biosciences International SARL

NCT02923349

/ Completed临床1/2期

A Phase 1/2, Open-Label, Dose-Escalation, Safety and Tolerability Study of INCAGN01949 in Subjects With Advanced or Metastatic Solid Tumors

The purpose of this study is to determine the safety and tolerability and assess preliminary efficacy of INCAGN01949 in subjects with advanced or metastatic solid tumors.

开始日期2016-10-31

申办/合作机构

Incyte Biosciences International SARL

100 项与 INCAGN-1949 相关的临床结果

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100 项与 INCAGN-1949 相关的转化医学

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100 项与 INCAGN-1949 相关的专利（医药）

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项与 INCAGN-1949 相关的文献（医药）

2022-10-01·Journal for immunotherapy of cancer

First-in-human phase I/II, open-label study of the anti-OX40 agonist INCAGN01949 in patients with advanced solid tumors

Article

作者: Orcurto, Angela ; Clark, Jason ; Vieito, Maria ; Davis, Elizabeth J ; Cho, Daniel C ; Kristeleit, Rebecca ; Condamine, Thomas ; Mehnert, Janice M ; Blagden, Sarah P ; Miller, Rowan E ; Chen, Xuejun ; Pulini, Jennifer ; Hari Dass, Prashanth ; Martin-Liberal, Juan ; Berthold, Dominik ; Janik, John E ; Cardin, Dana B ; Spencer, Kristen

Background:

OX40 is a costimulatory receptor upregulated on antigen-activated T cells and constitutively expressed on regulatory T cells (Tregs). INCAGN01949, a fully human immunoglobulin G1κ anti-OX40 agonist monoclonal antibody, was designed to promote tumor-specific immunity by effector T-cell activation and Fcγ receptor-mediated Treg depletion. This first-in-human study was conducted to determine the safety, tolerability, and preliminary efficacy of INCAGN01949.

Methods:

Phase I/II, open-label, non-randomized, dose-escalation and dose-expansion study conducted in patients with advanced or metastatic solid tumors. Patients received INCAGN01949 monotherapy (7–1400 mg) in 14-day cycles while deriving benefit. Safety measures, clinical activity, pharmacokinetics, and pharmacodynamic effects were assessed and summarized with descriptive statistics.

Results:

Eighty-seven patients were enrolled; most common tumor types were colorectal (17.2%), ovarian (8.0%), and non-small cell lung (6.9%) cancers. Patients received a median three (range 1–9) prior therapies, including immunotherapy in 24 patients (27.6%). Maximum tolerated dose was not reached; one patient (1.1%) receiving 350 mg dose reported dose-limiting toxicity of grade 3 colitis. Treatment-related adverse events were reported in 45 patients (51.7%), with fatigue (16 (18.4%)), rash (6 (6.9%)), and diarrhea (6 (6.9%)) being most frequent. One patient (1.1%) with metastatic gallbladder cancer achieved a partial response (duration of 6.3 months), and 23 patients (26.4%) achieved stable disease (lasting >6 months in one patient). OX40 receptor occupancy was maintained over 90% among all patients receiving doses of ≥200 mg, while no treatment-emergent antidrug antibodies were detected across all dose levels. Pharmacodynamic results demonstrated that treatment with INCAGN01949 did not enhance proliferation or activation of T cells in peripheral blood or reduce circulating Tregs, and analyses of tumor biopsies did not demonstrate any consistent increase in effector T-cell infiltration or function, or decrease in infiltrating Tregs.

Conclusion:

No safety concerns were observed with INCAGN01949 monotherapy in patients with metastatic or advanced solid tumors. However, tumor responses and pharmacodynamic effects on T cells in peripheral blood and post-therapy tumor biopsies were limited. Studies evaluating INCAGN01949 in combination with other therapies are needed to further evaluate the potential of OX40 agonism as a therapeutic approach in patients with advanced solid tumors.

Trial registration number:

NCT02923349.

2020-11-01·Gynecologic oncology reports

Sequential therapy with INCAGN01949 followed by ipilimumab and nivolumab in two patients with advanced ovarian carcinoma

作者: Cho, Daniel C ; Moiseyenko, Andrey ; Muggia, Franco ; Pulini, Jennifer ; Janik, John E ; Condamine, Thomas

Agonists of the co-stimulatory molecule OX40 (CD134) are in clinical assessment alone and in combination with other immunotherapies. Recent pre-clinical studies have suggested that concurrent administration of OX40 agonists with anti-PD1 therapy is detrimental to the efficacy of such combinations and maximal efficacy may require sequential administration of the OX40 agonist followed by anti-PD1 therapy. In this report, we detail two patients with advanced ovarian carcinoma were treated with INCAGN01949, an agonistic OX40 Ab, as part of a clinical trial until disease progression. Both patients then received the combination of ipilimumab and nivolumab and experienced unusually deep and durable responses. These cases support the hypothesis raised in pre-clinical studies and highlight the potential relevance of sequence in combinational immunotherapy.

项与 INCAGN-1949 相关的新闻（医药）

2026-09-10

·十亿分子

垂死病中惊坐起：OX40激动剂“起死回生”？

近期的药物研发进展是意外重重：先是诺和诺德重金买下的 IL-6 用于 ASCVD 一败涂地，再是 Lp(a) 抑制剂未达心血管事件终点，随后诺华 120 亿美金的 AOC 三期“意外”落马（具体亦可参考本公众号前述文章）。好不容易等来一个阳性新闻，却是 OX40 激动剂联合 K 药在头颈癌中意外翻盘。之所以称其意外，是因为 IO 激动剂这一概念在过去数年屡遭滑铁卢。读到新闻标题，颇有“垂死病中惊坐起，笑问客从何处来”之感。不过还是值得仔细分析分析表面数据背后的逻辑和细节。一、OX40 抗肿瘤药物研发总结1.1　OX40：一个“踩油门”的共刺激受体 OX40（CD134，TNFRSF4）是肿瘤坏死因子受体超家族（TNFRSF）成员，主要表达于活化的 CD4⁺/CD8⁺ T 细胞表面，属典型的共刺激受体。与抑制性检查点（如 PD-1/PD-L1）不同，OX40 通路的生理作用在于正向放大 T 细胞应答：其激活可促进 T 细胞增殖、存活与效应分化，诱导记忆 T 细胞生成，并抑制或清除 Foxp3⁺ 调节性 T 细胞（Treg）。因此，早在十余年前，OX40 即被视为 PD-1 之后肿瘤免疫领域的重要靶点。然而，该靶点的临床转化远较预期困难。OX40 的天然配体 OX40L（CD252，TNFSF4）为同源三聚体，受体激活依赖于高阶聚簇的形成（“三聚体之上的三聚体”/超分子簇），进而募集 TRAF2/3/5 衔接蛋白，激活 NF-κB、PI3K/AKT 与 NFAT 等下游信号通路。针对这一受体超家族，二价抗体存在固有缺陷：仅能介导受体的二聚化，远达不到天然配体所诱导的聚簇程度，单靠 Fab 结合不足以充分激活下游信号。由此，传统激动型抗体只能依赖 Fc 段与 Fcγ 受体（尤其是 FcγRIIB）的交联，借旁观免疫细胞将抗体–受体复合物进一步聚集；但此类二级交联在体内效率有限、高度依赖微环境，且不稳定。更进一步，该设计面临“条件性激动”的两难：TNFRSF 激动型抗体（含 OX40）的体内激动活性依赖 FcγR 交联，而提供“脚手架”式交联的关键是抑制性受体 FcγRIIB（ITIM 型，仅提供交联、不触发杀伤）；真正介导 ADCC/ADCP 的则是激活性受体 FcγRIIA/IIIA，可能清除本应被激活的 T 细胞（对 OX40 而言，亦有临床前研究提示 Fc 依赖的 Treg 清除反而是其抗肿瘤机制之一）。普通 IgG1 同时结合两类受体，“获得 FcγRIIB 交联”与“避免激活性 FcγR 杀伤”难以兼得——这正是“条件性激动型抗体”（选择性增强 FcγRIIB 结合、削弱激活性 FcγR 结合）工程化设计所要解决的矛盾。1.2　折戟名单：MNC 的集体滑铁卢下表汇总了主要 OX40 激动剂抗体的临床结局（数据来自 2025 年 Frontiers in Oncology 综述及各公司披露）：分子开发方形式/设计关键临床结果结局 PF-04518600 (ivuxolimab) 辉瑞 IgG2（低 FcγR 亲和）单药 ORR 约 5.8%（n=142）；剂量爬升仍不见外周 T 细胞激活信号，且提前出现 ≥3 级肝毒性因缺乏 FcγR 交联、疗效与毒性不匹配而终止 MOXR0916 罗氏/Genentech IgG1（人源化）单药 ORR 1.2%（n=172）、DCR 66%；瘤内 OX40⁺ T 细胞比例低 2019.11 因 3 级皮疹/腹泻阻断剂量爬升而停止 GSK3174998 GSK IgG1（人源化）单药 ORR 0%（n=45）；联合帕博利珠 ORR 8%（n=96）因疗效不足终止开发 MEDI0562 阿斯利康/MedImmune IgG1（人源化）单药 ORR 4%（n=55）；≥3 级免疫相关不良事件率高达 22% 无客观获益，终止 INCAGN01949 Incyte/Agenus IgG4 + FcγR 增强单药 ORR 1.5%（n=87），外周/瘤内药效信号微弱，9% 出现 3 级皮疹 2022 年终止 MEDI6469 (9B12) MedImmune 鼠源 IgG1（新辅助）头颈鳞癌新辅助（n=17）：3 年 OS 82%、DFS 71%，耐受良好留下 HNSCC 早期信号，未推进注册 BGB-A445 百济神州非配体阻断型 IgG1 单药 ORR 4%；联合替雷利珠单抗 ORR 23%（n=30，7 PR）管线移除注：PF-04518600、MOXR0916、GSK3174998、MEDI0562、INCAGN01949 等均为传统二价抗体，其单药 ORR 普遍落在 0–5% 区间，与安慰剂无异。1.3　失败原因的共性归纳综合上述案例，OX40 激动剂的失败可归纳为三点：药效学信号不足：二价抗体在体内无法形成足够的高阶受体聚簇，T 细胞增殖与激活信号微弱，未能产生可检测的药效学应答；剂量限制性毒性：为提高激动强度而增大剂量，诱发皮疹、腹泻、肝损伤等免疫相关不良事件（irAE），治疗窗口狭窄；联合用药缺乏协同且叠加毒性：与 PD-1 抑制剂等联用未见协同获益，反而放大了安全性问题。概言之，OX40 既往的失败源于分子与临床两个层面的叠加：分子层面，二价结构的固有局限决定了受体聚簇与下游信号不足；临床层面，剂量–毒性平衡与联合方案的优化均未实现。二、本次研究分析2.1　HexAgon 研究设计 2026 年 9 月 8 日，Inhibrx 公布 HexAgon 研究 II 期部分的主要终点数据。该研究为随机对照设计，比较六价 OX40 激动剂 INBRX-106 联合帕博利珠单抗与帕博利珠单抗单药，用于初治、PD-L1 阳性（CPS ≥ 20）、转移性或不可切除复发性头颈鳞癌（HNSCC）的一线治疗。研究在美、欧、亚 80 余个中心开展，II 期部分共随机 68 例，其中 63 例可评估主要终点（联合组 29 例，含 HPV⁺ 10 例；对照组 34 例，含 HPV⁺ 9 例），两组基线预后因素基本均衡。对照组采用帕博利珠单抗单药，为 KEYNOTE-048 所确立的一线 PD-L1 高表达 HNSCC 标准治疗。因此，本研究是对现行标准治疗的直接对照，其证据强度高于既往的单臂探索性研究。2.2　核心数据：ORR 近翻倍，且缓解具备深度与持久性疗效终点（全人群） INBRX-106 + K药 K药单药差值确认客观缓解率 cORR 48.3%（14/29） 26.5%（9/34） ≈ +1.8 倍完全缓解 CR 13.8%（4 例） 0 — 中位 PFS（中期） 9.6 个月 4.9 个月 +4.7 个月 6 个月 PFS 率 72.4% 42.8% +29.6 pp HPV 阳性亚组（病毒抗原驱动的高免疫原性肿瘤）的数据更为突出： HPV⁺ 亚组 INBRX-106 + K药（n=10） K药单药（n=9） cORR 80.0% 33.3% CR 率 30.0% 0% 6 个月 PFS 率 90.0% 33.0% 中位 PFS 尚未达到 4.6 个月安全性方面，最常见的治疗相关不良事件为皮疹、疲劳与腹泻，以低级别为主，整体可控，未见治疗相关死亡。据公司管理层披露，其安全性特征与 KEYNOTE-048 中帕博利珠单抗单药组相近。2.3　辅助证据：15 倍 T 细胞扩增（药效学验证）相较疗效终点，更值得关注的是药效学（PD）数据。2026 年 5 月中期分析显示，联合组患者外周血 CD8⁺/CD4⁺ T 细胞增殖最高达 15 倍、激活最高达 4 倍；对照组（帕博利珠单抗单药）分别仅为 2.5 倍与 1.5 倍。管理层在电话会中指出，既往 OX40 项目在部分患者中的 T 细胞扩增通常仅为 2–5 倍，且未转化为有意义的临床应答。 “药效学与临床应答之间的高度一致，使我们更有信心该信号真实，并具备跨适应症的可复制性。”——Inhibrx CEO Mark Lappe 对于Inhibrx，INBRX-106 首次在人体中实现了高倍率、可定量的 T 细胞扩增，并进一步转化为完全缓解与持久的无进展生存获益。2.4　成功归因的三层分析 ① 分子层面INBRX-106 基于 Inhibrx 专有的单域抗体（sdAb）平台构建，含六个 OX40 结合域，可同时结合多个 OX40 受体，无需 Fc 交联即可诱导受体自主聚簇，实现天然 OX40L 所具备的高阶聚簇，从而强效激活 T 细胞。临床前研究（Holay et al., J Immunother Cancer, DOI 10.1136/jitc-2025-011524）显示，六价分子在受体聚簇、NF-κB 信号、T 细胞增殖与 CD8⁺ 效应功能方面均优于二价激动剂，并在小鼠模型中产生显著的肿瘤消退与生存获益。 ② 适应症层面HPV⁺ 口咽鳞癌由病毒癌蛋白（E6/E7）驱动，属高免疫原性肿瘤：抗原负荷高、T 细胞浸润充分、PD-L1 高表达。这一背景为 OX40 共刺激提供了抗原特异性 T 细胞这一“底物”——只有预先存在抗原特异性 T 细胞，OX40 激动剂方能将其扩增为强效抗肿瘤应答。正如管理层所述：“HPV 阳性肿瘤具有高度免疫原性，当抗原存在时，OX40 共刺激即能真正放大应答。” ③ 联合与终点层面PD-1 阻断解除 T 细胞抑制，OX40 激动提供共刺激信号，二者机制互补；OX40 信号的核心价值在于记忆 T 细胞的诱导，这解释了本研究中完全缓解率（13.8%–30%）与 6 个月 PFS 的显著改善——其优势不仅在于缓解率，更在于缓解深度与持久性。三、核心问题：适应症选择，抑或分子价态？到底是适应症选得好，还是分子确实有特色？我觉得可能二者有之，适应症的贡献可能还大一些。3.1　假说一：适应症选择疗效分化高度集中于 HPV⁺ 亚组（80.0% vs 33.3%），全人群获益在很大程度上由该亚组贡献；既往唯一显示清晰临床信号的 OX40 试验亦发生于头颈鳞癌（MEDI6469 新辅助，3 年 OS 82%），提示 HNSCC 本身即为 OX40 的适宜适应症；在低免疫原性肿瘤中，即使分子具备强激动活性，亦可能因缺乏抗原特异性 T 细胞而无从发挥。3.2　假说二：分子价态该分子画风真的很清奇：既往二价分子在免疫原性并不低的适应症中亦告失败（GSK3174998 联合帕博利珠单抗 ORR 仅 8%；PF-04518600、MOXR0916、MEDI0562 单药 ORR 0–5%），正常二价抗体的药效学信号确实也是值得怀疑；根据2026年5披露的信息，临床病人中六价分子联合K药诱导的 T 细胞扩增幅度约为15倍，而K药组是2-3倍扩增；较好的证明了联合后，该分子增加的T细胞活性。当然，这里有个疑问，一般外周T扩增也会带来较强的免疫相关副作用，但似乎昨天透露的信息中，公司管理层对临床的安全性很有信心。最后，临床前同瘤种、同背景的头对头比较中，六价显著优于二价，表明“价态”本身即为独立变量。 INBRX-106在临床前研究中，展现出较2，3，4价更强的激活信号水平。外周T细胞激活实验，六价分子也显示更强的激活水平。当然，这些都是体外的验。病人的T细胞变化仅在一些PR中提到，未见到数据。3.3 综合判断：六价聚簇临床前和临床均有证据显示更强的激活水平，但我们也要注意到目前适应症的一些背景；HPV⁺、高 PD-L1 的头颈鳞癌提供了抗原充足、T 细胞浸润、PD-L1 高表达的有利背景，得以显现的放大激活。加之 PD-1 联合与记忆 T 细胞诱导带来的深度、持久获益，三者的共同作用方才促成此次缓解率的近翻倍。更具体地，可从三个层面理解： 4.分子决定“能否激活”：缺乏六价高阶聚簇，OX40 通路在人体内难以被充分激活，任何适应症均难以弥补——此为历史失败的第一性原因。 5.适应症决定“激活的效应大小”：仅在抗原充足、T 细胞浸润的免疫原性肿瘤中，被激活的 T 细胞方有明确的攻击靶点，信号方能放大至统计学显著。 6.联合与终点决定“获益的程度”：PD-1 阻断解除衰竭 T 细胞的抑制，OX40 的记忆诱导属性将缓解转化为持久缓解，直接贡献于 CR 率与 PFS 的改善。需要说明的是：由于既往二价 OX40 激动剂未曾在一线 HPV⁺ 头颈鳞癌联合 PD-1 的精确场景中进行随机对照，现有数据尚不能完全排除“仅依赖适应症选择与二价分子亦可取得类似效果”的可能性。四、展望与风险4.1　后续开发与商业信号注册路径：Inhibrx 计划在 II 期部分扩组约 50 例 HPV⁺ 口咽鳞癌（OPSCC，CPS≥1），以支持加速批准；随后启动 HexAgon III 期作为确证性研究，并与 FDA 对齐框架。管理层认为，该数据足以支持基于随机 II 期研究的突破性疗法认定与加速批准。拓展方向：围手术期非小细胞肺癌（NSCLC）I/II 期（首批数据预计 2027 年中）、一线转移性 NSCLC，以及与治疗性肿瘤疫苗、T 细胞衔接器、CAR-T 的联合。商业信号：据路透社 4 月报道，默沙东、德国默克、小野制药等对 INBRX-106 表现出兴趣，该资产估值约 80 亿美元；连同四价 DR5 激动剂 ozekibart（INBRX-109，已提交 BLA，PDUFA 日期 2027-04-14），整体交易价值或超 90 亿美元。考虑到帕博利珠单抗 2025 年销售额约 317 亿美元、且 2028 年面临专利悬崖，INBRX-106 具备延长其生命周期、形成组合的潜力。4.2　风险分析样本量有限：全人群 63 例可评估，HPV⁺ 亚组仅 19 例（联合组 10 例），80% 的 ORR 对应较宽置信区间，该亚组数据应视为强信号而非定论；数据尚未成熟：中位 PFS（尤其是联合组）仍在随访中，最终数据可能回落；同类靶点历史：OX40 赛道十余年缺乏临床获益，单次 II 期结果尚不足以完全改变市场判断，仍需 III 期确证；4.3　结语 OX40 这一被多家跨国药企反复验证失败的靶点，首次在随机对照研究中显示出清晰获益。该阳性数据的获得，除了分子的高度差异化之外，也有一定适应症方面的优势。能否拓展到别的适应症，尤其是NSCLC还需要更多的临床研究。但总体给我的感觉，IO激动剂抗体的市场价值和应用场景还是比较有限的。参考来源 [1]Inhibrx 官方新闻稿（2026-09-08）：INBRX-106 Nearly Doubles Response Rate and Achieves Interim Median PFS of 9.6 months in Phase 2 HNSCC Studyhttps://inhibrxbiosciences.investorroom.com/2026-09-08-Inhibrxs-INBRX-106-Nearly-Doubles-Response-Rate-and-Achieves-Interim-Median-PFS-of-9-6-months-in-Phase-2-HNSCC-Study [2]Fierce Biotech：Inhibrx CEO says progression-free survival data leave 'no question' about OX40 agonist's durabilityhttps://www.fiercebiotech.com/biotech/inhibrxs-profound-dataset-boosts-hopes-accelerated-approval-ox40-agonist [3]微信公众号文章：六价 OX40 激动剂 INBRX-106 联合 K药 II 期数据 [4]Elpiscience（科望医药，ES102 大中华区权益方）中期数据与药效学披露https://www.elpiscience.com/new/interim-phase-2-data-for-hexavalent-ox40-agonist-combination-therapy-in-first-line-hnscc-demonstrate-potential-benefit--over-pd-1-monotherapy.html [5]Holay N, Yadav R, et al. INBRX-106: a hexavalent OX40 agonist that drives superior antitumor responses via optimized receptor clustering. J Immunother Cancer（DOI 10.1136/jitc-2025-011524）https://digitalcommons.providence.org/publications/10496/ [6]Frontiers in Oncology（2025）：OX40/OX40L: a new target for tumor immunotherapy and its clinical research progress（含各失败分子的临床结局表）https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2025.1730620/full [7]网易/药时空（2026-09-09）：II期临床大成功，默沙东欲掷80亿美元收购（含 M&A、K药专利悬崖背景）https://www.163.com/dy/article/L6D0HFD00532CO9S.html [8]AllSci（2026-09-08）：Inhibrx's OX40 agonist nearly doubles response rate（含 KEYNOTE-048、petosemtamab 竞品背景）https://allsci.com/news/clinical-trials/inbrx-106-head-and-neck-cancer-inhibrxs-nearly/ 免责声明：本报告基于公开信源整理与分析，仅供行业研究参考，不构成任何投资建议或诊疗建议。所引数据以原始披露为准；II 期中期数据存在样本量小、随访未成熟等局限，最终结论需待 III 期确证性研究验证。

临床3期免疫疗法

2026-01-20

·星际微光

冷肿瘤免疫疗法获投1.41亿美金！Agenus联手Zydus加速III期临床和全球商业化

2026年1月，免疫肿瘤企业Agenus宣布与Zydus Lifesciences达成1.41亿美元战略合作，推动其免疫治疗组合BOT+BAL的全球开发及商业化。交易包括7500万美元现金、1600万美元股权投资及最多5000万美元里程碑付款，Zydus还获得该组合在印度和斯里兰卡的独家权利。 Agenus保留美国生产能力，支持其全球III期注册试验BATTMAN在MSS结直肠癌领域的推进。BOT+BAL此前在临床中显示出显著生存优势，合作将进一步强化其供应链及全球商业化布局。有问题，问星光智能体！人类基地：惊天反转！“微塑料恐慌”是场科学乌龙？《自然》论文遭同行狠批！投资亮点一、产品价值验证与全球化加速 BOT+BAL组合是Agenus在免疫肿瘤领域的核心产品，已在晚期MSS结直肠癌患者中展现出中位总生存期21个月、2年生存率达42%的卓越数据，远超传统免疫疗法对“冷瘤”的治疗效果。此次交易代表全球市场，尤其是新兴市场（如印度）的潜在合作方已充分认可其临床价值。 Zydus获得该组合在印度与斯里兰卡的独家商业化权利，将极大推动Agenus在发展中国家的市场渗透，同时Agenus可通过5%的销售提成（royalty）长期受益。二、释放非核心资产、优化现金流 Agenus将位于加州的两处生物药生产设施出售给Zydus，获得7500万美元现金，进一步改善其资产负债表和现金流状况，有助于支撑其III期临床和注册申报开支。此外，Agenus无需完全退出制造能力，而是通过本次协议保留长期生产配额（committed capacity），实现“资产轻”但“控制强”的灵活制造策略，降低运营负担的同时保障药物供应。三、通过股权投资绑定战略合作关系 Zydus同时以每股7.5美元价格，认购了Agenus价值1600万美元的股份，成为战略股东。这一安排既体现出Zydus对BOT+BAL组合长期前景的信心，也增强了双方合作的粘性与协同动力。四、未来里程碑收入与产能收益具潜力该协议还包含最高5000万美元的产能激励（milestone payments），未来随着BOT+BAL进入商业化阶段或临床试验扩大，Agenus有望获得额外现金流补充。而Zydus新成立的Zylidac Bio LLC不仅承接制造设施，还将面向全球提供CDMO服务，为其自身打开新的营收渠道。五、Agenus战略聚焦，提升执行力本次合作使Agenus能集中资源推进其III期注册临床试验BATTMAN项目，这是面向MSS结直肠癌的一项关键性全球注册研究，预计覆盖100+国际临床中心。此次交易正值其商业化前夜，及时补充资源和产能，有助于其加速向全球监管申报与早期支付机制（如法国AAC）推进。 Agenus的价值分析一、产品优势：差异化免疫组合疗法BOT+BAL 核心产品为BOT（Botensilimab）+ BAL（Balstilimab）组合，针对传统免疫治疗无效的“冷瘤”（如MSS结直肠癌）展现出显著疗效。多项临床试验（包括NEST-1、NEOSIS、BATTMAN）数据支持其在多种实体瘤（结直肠癌、卵巢癌、软组织肉瘤等）中具有深度和持久的应答率。可用于新辅助治疗、三线及更晚期治疗，具备较强的适应症扩展潜力。二、技术优势：创新靶点机制+ 免疫系统双向激活 1、BOT为增强型Fc抗体，可激活先天+适应性免疫，包括T细胞、髓系细胞和记忆免疫反应。 2、BAL为高亲和力PD-1单抗，具备良好的安全性和耐受性，且与BOT形成互补协同。 3、重点突破“免疫耐药肿瘤”，填补目前PD-1/PD-L1疗法无效人群的治疗空白。三、平台优势：完整的端到端免疫药物研发体系 1、拥有自研抗体库、细胞治疗平台、疫苗佐剂平台，形成组合式创新研发策略。 2、具备临床前至III期、全球临床操作、以及GMP生产设施（部分已转让但保留产能）。 3、多管线协同，具备开发下一代免疫组合药的强大平台能力。四、服务优势：多样化患者可及路径 1、在法国、美国等国家开通早期使用通道（如AAC），并由国家医保全额报销（法国）。 2、开展“付费命名患者计划”，在尚未获批国家通过商业化路径提供药品，提升可及性。 3、提供清晰的患者教育与用药资源，强调对患者结果负责的企业文化。五、商业模式：核心产品主导+ 灵活合作 1、核心管线BOT+BAL由Agenus主导开发与全球布局，但通过与Zydus、Ligand等企业合作，释放非核心资产、引入资金并拓展区域市场。 2、高度灵活的交易结构，包括股权、产能换现金、授权换提成等方式，优化资源配置。 3、通过CDMO、License-out等方式，建立稳定的现金流支撑创新投入。六、医疗价值：面向“免疫盲区”人群的转化疗法 1、针对目前免疫治疗获益较低的MSS结直肠癌、复发难治卵巢癌、软组织肉瘤等人群提供新疗法。 2、以“免疫组合治疗”理念，推动从一线至新辅助等全治疗周期的应用，提升患者长期生存。 3、有望替代传统放化疗、减少手术需求，改变部分实体瘤的治疗范式。七、未来前景：数据驱动注册、全球化商业加速 1、正在推进全球注册III期试验（BATTMAN），预计将成为MSS CRC领域首个获批免疫疗法。 2、法国、加拿大、澳洲等国临床基地已激活，全球化布局逐步落地。 3、公司愿景是成为冷瘤免疫治疗的领导者，预计BOT+BAL首个适应症峰值销售潜力超10亿美元，后续有望在更多瘤种中复制成功路径。癌症免疫循环一、核心科学理念：调动人体免疫系统抗癌与传统治疗手段（化疗、放疗、手术）不同，Agenus的免疫疗法（IO）目标是利用人体自身免疫系统识别并清除癌细胞，同时保护正常细胞，减少长期副作用和并发症。其治疗逻辑紧密围绕“癌症免疫循环（Cancer Immunity Cycle）”设计，分为以下几个阶段： 1、识别与启动（Priming & Activation）：肿瘤通过多种机制“伪装”以逃避免疫系统。Agenus的药物能够“揭示”隐藏肿瘤，激活T细胞等免疫因子。 2、持续攻击与清除（Sustained Attack & Elimination）：其免疫调节剂可维持免疫活性，直到彻底清除癌细胞并建立免疫记忆，防止复发。二、关键技术组合：BOT + BAL 联合疗法 Agenus目前的明星产品组合为： 1、Botensilimab (BOT)：一种Fc结构增强型抗CTLA-4抗体，不仅激活T细胞，还可重新编程抑制性免疫微环境，提高对“冷瘤”的免疫应答。 2、Balstilimab (BAL)：一种高亲和力的PD-1抑制剂，可阻断肿瘤诱导的T细胞“疲劳”，恢复其攻击能力。这两种免疫检查点抑制剂协同作用，可实现更深层次、更持久、更广谱的抗肿瘤反应。该组合正在进行全球III期临床（BATTMAN试验），用于MSS型结直肠癌治疗。三、科学创新点总结项目描述治疗机制不依赖直接杀伤肿瘤，而是激发机体自身免疫力清除癌细胞，具有“训练+记忆”功能。靶点技术创新性双靶点（CTLA-4 + PD-1）联用，增强免疫激活同时降低毒副作用。治疗人群针对传统疗法效果不佳的“冷瘤”如MSS 结直肠癌、卵巢癌、软组织肉瘤等。疗效特征临床研究显示治疗反应更深、更持久，部分患者可达完全缓解（CR）或病理完全缓解（pCR）。长期防复发强调“免疫记忆”机制，治疗后仍能维持抗肿瘤警觉性，有效减少复发率。四、平台化布局与战略协同 Agenus的IO 管线围绕免疫循环多个环节布局，除了BOT+BAL组合，还拥有多个早期单抗、联合免疫方案、疫苗佐剂平台等技术储备。致力于实现组合免疫治疗平台化发展，并推动多适应症拓展。与多国临床试验网络及战略伙伴合作，加快临床开发与注册步伐。 Agenus的Pipeline 一、总体概况：布局全面、靶点创新、组合策略清晰 Agenus作为一家临床阶段的免疫肿瘤公司，其产品管线围绕癌症免疫循环多个关键环节布局，开发具有互补机制的免疫疗法。核心特色是： 1、多靶点联合策略（CTLA-4 + PD-1为核心） 2、多适应症并行推进，重点在“冷瘤”领域 3、多个药物进入2期/3期，具备中后期商业转化潜力二、明星产品组合：BOT + BAL 1、药物信息： Botensilimab（AGEN1181）：Fc增强型抗CTLA-4抗体，具多机制增强免疫激活 Balstilimab：人源化PD-1单抗，已验证安全性良好 2、临床布局：适应症项目名称阶段状态 MSS转移性结直肠癌（四线以上） BATTMAN III期进行中（全球多中心） MSS mCRC 非肝转移（三线） C-800-25 II期已完成招募新辅助mCRC NEST / 24-389 II期已招募/ 招募中胰腺癌（联合化疗） C-800-22 II期已完成招募多种肿瘤新辅助治疗 NEOASIS II期招募中一线MSS CRC UNICORN / FOLFOX组合 II期招募中复发/难治黑色素瘤未命名 II期开展中亮点：该组合在MSS-CRC（一种传统免疫耐药瘤种）中展现突破性疗效，具备First-in-Class潜力。三、多靶点免疫资产布局（早期产品）药物代号靶点联合策略适应症阶段 AGEN2373 CD137激动剂 ± BOT 实体瘤、黑色素瘤 I/II期 AGEN1571 抗ILT-2 ± BOT/BAL 实体瘤 I期 AGEN1777 双特异抗体（TIGIT × CD96） + BAL 实体瘤 I期 AGEN1423 CD73 × TGF-β 双靶点抗体单药实体瘤 I期 AGEN1949 OX40激动剂单药实体瘤 I期 INCAGN1876 GITR激动剂单药实体瘤 I期亮点：Agenus通过多个激动性抗体、双靶点抗体等新兴免疫机制补强产品线，有望实现未来免疫组合个性化治疗。四、平台策略与临床转化特色组合治疗为主线：几乎所有资产均为联合疗法开发，强调协同机制。适应症聚焦“免疫盲区”：优先布局传统免疫无效癌种（如MSS CRC、胰腺癌等）。新辅助治疗探索活跃：尝试通过免疫疗法提升早期肿瘤治疗反应率与根治率。合作广泛：与CCTG、Weill Cornell、Duke、MSKCC、City of Hope等全球顶尖肿瘤中心合作开展临床。欲深入了解更多行业洞察，请扫以下二维码加入社群：公司已完成项目星际微光已完成的项目（截至2023.9，仍在继续......）圆满中秋 | 星际微光七年完成100个咨询项目咨询、调研、PR、投资、融资、营销、技术转化项目需求请扫码联系我们：点击“阅读原文”，看看：全身MRI是虚假的安全感吗？

免疫疗法临床3期AACR会议引进/卖出临床结果

2023-05-09

·Business Wire

Agenus Provides Corporate Update and First Quarter 2023 Financial Results

LEXINGTON, Mass.--( BUSINESS WIRE )--Agenus Inc. (Nasdaq: AGEN), an immuno-oncology company with an extensive pipeline of clinical and preclinical-stage cancer treatments, today provided a corporate update and reported financial results for the first quarter 2023. "With over 350 patients dosed with botensilimab in our Phase 1 study, we have demonstrated 20-50% response rates in 9 solid tumor cancers. These results suggest that botensilimab could provide significant benefit to patients who have not responded to or failed other available treatments,” said Dr. Garo Armen, Chief Executive Officer of Agenus. “Agenus is committed to advancing our development programs to make botensilimab available to patients ASAP." Botensilimab Combination Unprecedented activity in 70 patients with non-MSI-H colorectal cancer and 24 patients with recurrent platinum resistant/refractory ovarian cancer : Agenus presented botensilimab/balstilimab combination data at a late-breaking oral session at the American Society of Clinical Oncology – Gastrointestinal Cancers Symposium (ASCO-GI) in January 2023 and at the Society of Gynecologic Oncology (SGO) 2023 Annual Meeting on Women’s Cancer in March 2023 The combination showed unprecedented responses and survival benefit in 70 patients with non-microsatellite instability-high (non-MSI-H) colorectal cancer, including: 12-month overall survival of 63% (compared to 25% reported for standard of care) 1,2 Overall response rate of 23% (compared to 1-2% 1,2 reported for standard of care and 1-5% 3,4 reported for other PD-(L)1 + CTLA-4 combinations) In April 2023, the FDA granted Fast Track Designation to the botensilimab/balstilimab combination for the treatment of non-MSI-H/deficient mismatch repair (dMMR) metastatic colorectal cancer patients without active liver involvement who are resistant or intolerant to fluoropyrimidine, oxaliplatin, or irinotecan, and have also received a VEGF inhibitor, an EGFR inhibitor, and/or a BRAF inhibitor Agenus is conducting a global, randomized Phase 2 trial in this patient population under its ACTIVATE trial program, and a global Phase 3 trial is expected to commence in 2023 In 24 ovarian cancer patients who were resistant or refractory to platinum chemotherapy, the botensilimab/balstilimab combination showed a 33% response rate (compared to ~10% reported for standard of care 5 and 3-10% for other PD-(L)1 + CTLA-4 combinations 6,7 ) Agenus continues to enroll PD-(L)1 relapsed/refractory NSCLC patients in its Phase 1b study and plans to launch a randomized phase 3 study if the previously reported ~50% response rates continue Upcoming Presentations Updated data on the botensilimab/balstilimab combination in non-MSI-H metastatic colorectal cancer patients selected for a late breaking oral presentation at the upcoming ESMO World Congress on Gastrointestinal Cancer (ESMO-GI), to be held June 18 – July 1, 2023 in Barcelona, Spain Data from a single-arm, open-label Phase 2 study of balstilimab and zalifrelimab (1 st generation CTLA-4) plus doxorubicin in patients with advanced sarcomas selected for oral presentation at the ASCO 2023 Annual Meeting, to be held June 2-6 in Chicago, IL Complete results from the monotherapy arm of the first-in-human dose escalation study of AGEN2373 in patients with advanced solid tumors will also be presented in a poster discussion at ASCO Clinical Pipeline and Corporate Partnerships Additional presentation at ASCO involving Agenus's clinical pipeline involving collaborations include: Abstract #424868: Targeting minimal residual disease (MRD) in resected RAS mutated pancreatic cancer with vaccine TG01/QS-21 +/- PD-1 inhibitor, balstilimab: A randomized phase II study (TESLA) Abstract # TPS6104: Phase 2 Trial of Retifanlimab (anti–PD-1) in Combination With INCAGN02385 (anti–LAG-3) and INCAGN02390 (anti–TIM-3) as First-Line Treatment in Patients With PD-L1–Positive Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck Abstract #2599: A Phase 1/2 Study of retifanlimab (INCMGA00012, Anti–PD-1), INCAGN02385 (Anti–LAG-3), and INCAGN02390 (Anti–TIM-3) Combination Therapy in Patients (Pts) With Advanced Solid Tumors Abstract #2541: A phase 1/2 study of the safety, tolerability, and preliminary efficacy of the anti-GITR monoclonal antibody, INCAGN01876, combined with immunotherapies (IO) in patients (Pts) with advanced cancers Agenus shareholders received dividend of shares in MiNK Therapeutics (NASDAQ: INKT) On May 1 st , 2023, Agenus distributed a dividend of approximately 5,000,000 shares it owned of its subsidiary MiNK Therapeutics’ common stock to shareholders who held Agenus shares as of April 17, 2023, with a ratio of 0.0146 shares of MiNK (NASDAQ: INKT) per share of Agenus. The announced dividend distribution preceded MiNK's presentation of its lead product, agenT-797 , an allo-INKT cell therapy, showing clinical and biomarker responses in solid tumor cancers at AACR in April 2023. This distribution allows Agenus shareholders to benefit from future growth of MiNK through direct ownership. The shares that were distributed as part of this dividend were not part of a new stock offering. First Quarter 2023 Financial Results: We ended our first quarter 2023 with a cash, cash equivalent and short-term investment balance of $189.2 million, compared to $193.4 million at December 31, 2022. Since quarter end we have raised $13.6 million through sales under our at market issuance sales agreement. For the first quarter ended March 31, 2023, we recognized revenue of $22.9 million and incurred a net loss of $70.9 million (including non-cash expenses of $24.9 million) or $0.22 per share. Financial Highlights (in thousands, except per share data) (unaudited) March 31, December 31, 2023 2022 Cash, cash equivalents and short-term investments $ 189,233 $ 193,358 Three months ended March 31, 2023 2022 Revenues, research and development $ 2,612 $ 6,740 Revenues, non-cash royalty 19,106 17,634 Revenues, other 1,184 1,567 Total Revenue 22,902 25,941 Research and development expenses 57,118 42,442 General and administrative expenses 18,237 18,953 Cost of service revenue 2,294 543 Other (income) loss (721 ) 191 Non-cash interest expense 17,273 14,952 Non-cash contingent consideration fair value adjustment (406 ) (536 ) Net loss $ (70,893 ) $ (50,604 ) Net loss per share attributable to Agenus Inc. common stockholders $ (0.22 ) $ (0.19 ) Cash used in operations $ 58,526 $ 52,391 Non-cash operating expenses $ 24,935 $ 21,069 Conference Call Date : May 9, 2023, 8:30am ET Dial-in numbers : 646-307-1963 (US-NY) & 800-715-9871 (Ex-US) Event ID : 9144113 Webcast A webcast and replay of the conference call will be accessible from the Events & Presentations page of the Company’s website at https://investor.agenusbio.com/events-and-presentations and via https://edge.media-server.com/mmc/p/v54y2wy9 . References 1 Mayer et al. NEJM 2015 2 Grothey et al. Lancet 2013 3 Chen et al. JAMA Oncol. 2020 4 Overman et al. ASCO 2016 5 Mutch DG, et al. J Clin Oncol. 2007;25(19): 2811-2818 6 https://clinicaltrials.gov/ct2/show/results/NCT01928394 7 Hinchcliff et al. Gynecologic Oncology 2021 About Botensilimab Botensilimab is a novel, multifunctional CTLA-4 investigational antibody that has been designed to extend clinical benefits to “cold” tumors that have not historically responded to standard of care or investigational therapies, as well as to expand clinical benefit in “hot” tumors, where immunotherapies are approved but benefit only a minority of patients. In addition to binding to the CTLA-4 receptor, its Fc-enhanced structure induces a memory immune response, downregulates regulatory T cells, activates existing T cells, as well as primes and expands new T cells, thereby promoting a more effective and durable immune response to cancer. In a Phase 1 clinical study of more than 350 patients, botensilimab has demonstrated clinical responses in nine different cold and treatment-refractory solid tumor cancers, either alone or in combination with Agenus’ PD-1 antibody, balstilimab (data presented at ASCO GI 2023 , SGO 2023 , SITC 2022 , and CTOS 2022 ). Agenus is conducting global, randomized Phase 2 trials in non-MSI-H colorectal cancer, melanoma, and pancreatic cancer as part of its ACTIVATE trial programs. Additional information about these botensilimab trials can be found at www.clinicaltrials.gov under the identifiers NCT05608044 , NCT05630183 , and NCT05529316 , respectively. A global Phase 3 trial in non-MSI-H colorectal cancer is expected to launch in 2023. About AGEN2373 AGEN2373 is a novel anti-CD137 agonist that has been designed to activate T and NK cells while mitigating liver toxicities common to the CD137 target class. CD137 (4-1BB) is an activating receptor expressed on T and NK cells. Upon binging to CD137, AGEN2373 is designed to stimulate the growth and activation of cytotoxic T and NK cells, triggering a lasting memory response to cancer. AGEN2373 binds to a unique epitope designed to achieve this response specifically within the tumor microenvironment. This selective binding is designed to avoid serious side effects associated with CD137 activation in the liver that have been reported by competitor molecules. AGEN2373 has demonstrated preliminary clinical activity and has been well tolerated by patients without signs of liver toxicity (Tolcher et al. ASCO 2021). About Agenus Agenus is a clinical-stage immuno-oncology company focused on the discovery and development of therapies that engage the body's immune system to fight cancer and infections. The Company's vision is to expand the patient populations benefiting from cancer immunotherapy by pursuing combination approaches that leverage a broad repertoire of antibody therapeutics, adoptive cell therapies (through its subsidiary MiNK Therapeutics), and adjuvants (through its subsidiary SaponiQx). The Company is equipped with a suite of antibody discovery platforms and a state-of-the-art GMP manufacturing facility with the capacity to support clinical programs. Agenus is headquartered in Lexington, MA. For more information, please visit www.agenusbio.com and our Twitter handle @agenus_bio. Information that may be important to investors will be routinely posted on our website and Twitter. About MiNK Therapeutics MiNK Therapeutics is a clinical-stage biopharmaceutical company pioneering the discovery, development, and commercialization of allogeneic invariant natural killer T (iNKT) cell therapies to treat cancer and other immune-mediated diseases. MiNK is advancing a pipeline of both native and next-generation engineered iNKT programs, with a platform designed to facilitate scalable and reproducible manufacturing for off-the-shelf delivery. The company is headquartered in New York, NY. For more information, visit https://minktherapeutics.com/ and Twitter handle @MiNK_iNKT. Forward-Looking Statements This press release contains forward-looking statements that are made pursuant to the safe harbor provisions of the federal securities laws, including statements relating to our technologies, therapeutic candidates, and capabilities, for instance, statements regarding therapeutic benefit and efficacy, mechanism of action, potency, durability, and safety and tolerability profile of our therapeutic candidates, both alone and in combination with each other and/or other agents; statements regarding future plans, including research, clinical, regulatory, and commercialization plans; and any other statements containing the words "may," "believes," "expects," "anticipates," "hopes," "intends," "plans," "will" and similar expressions are intended to identify forward-looking statements. These forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially. These risks and uncertainties include, among others, the factors described under the Risk Factors section of our most recent Quarterly Report on Form 10-Q or Annual Report on Form 10-K filed with the Securities and Exchange Commission and available on our website: www.agenusbio.com . Agenus cautions investors not to place considerable reliance on the forward-looking statements contained in this release. These statements speak only as of the date of this press release, and Agenus undertakes no obligation to update or revise the statements, other than to the extent required by law. All forward-looking statements are expressly qualified in their entirety by this cautionary statement.

临床结果免疫疗法临床2期临床1期ASCO会议

100 项与 INCAGN-1949 相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
局部晚期恶性肿瘤	临床2期	美国	Incyte Biosciences International SARL	2017-10-09
转移性胃癌	临床2期	美国	Incyte Biosciences International SARL	2017-10-09
转移性实体瘤	临床2期	美国	Incyte Biosciences International SARL	2017-10-09
非小细胞肺癌	临床2期	美国	Incyte Biosciences International SARL	2017-10-09
头颈部鳞状细胞癌	临床2期	美国	Incyte Biosciences International SARL	2017-10-09
肾细胞癌	临床2期	美国	Incyte Biosciences International SARL	2017-10-09
晚期恶性实体瘤	临床2期	美国	Incyte Biosciences International SARL	2016-10-31
晚期恶性实体瘤	临床2期	西班牙	Incyte Biosciences International SARL	2016-10-31
晚期恶性实体瘤	临床2期	瑞士	Incyte Biosciences International SARL	2016-10-31
晚期恶性实体瘤	临床2期	英国	Incyte Biosciences International SARL	2016-10-31

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临床结果

适应症

分期

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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


NCT04387071 (CTgov)	临床1/2期	局部晚期恶性实体瘤 \| 转移性胰腺腺癌 \| 黑色素瘤 ... 更多	2	VLP-encapsulated TLR9 Agonist CMP-001+CMP-001+INCAGN01949	糧鏇顧顧觸願積壓鹹選 = 糧壓範襯構醖鏇襯廠齋餘齋積鏇積壓鹽齋淵遞 (構選窪製獵網醖齋範壓, 憲夢艱糧糧顧願鑰夢夢 ~ 製齋獵構壓構襯窪廠餘) 更多	-	2026-02-17
NCT02923349 (Pubmed)	临床1/2期	晚期恶性实体瘤	87	INCAGN01949 monotherapy	襯襯獵壓憲膚鏇獵鹽網(遞壓壓膚鹹繭憲壓夢鹽) = 6 (6.9%) 願願窪膚鬱獵壓選糧顧 (觸範鑰壓觸蓋獵遞糧蓋 ) 更多	不佳	2022-10-01
NCT02923349 (CTgov)	临床1/2期	转移性肿瘤 \| 晚期恶性实体瘤	87	INCAGN01949 (PART 1 Dose 1 (7 mg))	淵顧觸鹹網廠醖襯憲夢 = 蓋鑰觸構鬱襯蓋憲齋衊廠鹽選鏇鏇鏇製醖範蓋 (鏇廠憲獵鹽積艱築遞積, 構顧願襯簾願淵淵膚艱 ~ 簾廠鹹鏇衊獵製糧範顧) 更多	-	2020-05-12
NCT02923349 (CTgov)	临床1/2期	转移性肿瘤 \| 晚期恶性实体瘤	87	INCAGN01949 (PART 1 Dose 2 (20 mg))	淵顧觸鹹網廠醖襯憲夢 = 鏇鹽願遞觸醖構網蓋選廠鹽選鏇鏇鏇製醖範蓋 (鏇廠憲獵鹽積艱築遞積, 膚獵簾艱積鏇襯網積憲 ~ 鹹鹽膚鑰糧觸網繭製鬱) 更多	-	2020-05-12