Feasibility and Phase 2a Study of Relatlimab and Nivolumab (Opdualag™) in Adolescent and Young Adult Patients Newly Diagnosed With Replication Repair Deficient High-Grade Glioma (HGG), Including Diffuse Intrinsic Pontine Glioma (DIPG)

The goal of this study is to further evaluate feasibility and tolerability of Opdualag for patients with replication repair deficient HGG, including DIPG.

开始日期2027-03-01

申办/合作机构

Nationwide Children's Hospital

NCT07459543

/ Not yet recruiting临床4期

A Phase 4, Single Arm, Open Label Study to Evaluate Safety, Tolerability, and Efficacy of Nivolumab + Relatlimab Fixed-Dose Combination (FDC) in Participants With Unresectable or Metastatic Melanoma in India.

The purpose of this study is to assess the safety and tolerability of Nivolumab + Relatlimab Fixed-Dose Combination (FDC) in unresectable or metastatic melanoma participants in India.

开始日期2026-11-15

申办/合作机构

Bristol Myers Squibb Co.

NCT06319196

/ Recruiting临床2期IIT

Clear Me: Interception Trial to Detect and Clear Molecular Residual Disease in Patients With High Risk Melanoma

Clear-Me is a biomarker-driven phase II study that tests whether the combination anti- lymphocyte-activation gene-3 (LAG3)/anti-programmed cell death protein 1(PD-1) inhibition Bristol-Myers Squibb (BMS986213) is superior to anti-PD-1 inhibition in patients with detectable circulating tumor deoxyribonucleic acid (ctDNA) following definitive surgery for high risk melanoma. Patients will be allocated to either Arm A or Arm B via the process of randomization. The randomization process will be stratified according to stage (Stage 2A/2B/3A/3B/3C/3D or 4), to ensure absolute balance between stage groups. The investigators are choosing only 1 stratification factor, disease stage, as the investigators consider stage being the most significant prognosticating variable. Each stage represents a biologically distinct entity with varying recurrence rate outcomes. Block randomization will be performed to ensure equal sample sizes in the combination and monotherapy arms. At least 54 patients will be included in the randomized part of the study. The investigators are expecting approximately 20% of the patients to have detectable ctDNA after definite surgery. Therefore, approximately 270 patients are expected to be enrolled and tested for ctDNA in the entire study.

开始日期2026-08-27

申办/合作机构

University Health Network

100 项与纳武利尤单抗/瑞拉利单抗相关的临床结果

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100 项与纳武利尤单抗/瑞拉利单抗相关的专利（医药）

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项与纳武利尤单抗/瑞拉利单抗相关的文献（医药）

2025-11-26·Cureus Journal of Medical Science

Drug-Induced Bullous Pemphigoid Triggered by Immune Checkpoint Inhibitor Opdualag in an Elderly Patient With Recurrent Metastatic Melanoma: A Case Report and Treatment Course With Dupilumab

Article

作者: Lutwak, Moises ; Kerdel, Francisco ; Lutwak, Daniel ; Moreno, Brian A

Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disorder most commonly affecting elderly individuals and may be triggered by medications, including immune checkpoint inhibitors (ICIs). We present the case of an 81-year-old male with a history of recurrent metastatic melanoma previously treated with nivolumab and relatlimab (Opdualag), who developed a persistent pruritic eruption following initiation of dual PD-1/LAG-3 blockade. Despite discontinuation of immunotherapy six months before dermatologic evaluation and use of multiple topical corticosteroids and oral antihistamines, symptoms persisted. A punch biopsy and direct immunofluorescence demonstrated linear IgG and C3 deposition along the basement membrane zone, consistent with BP. On initial dermatologic examination, urticarial pink plaques involved approximately 50% of the body surface area, with lesions affecting the left medial inferior chest and epigastric region. Treatment with subcutaneous dupilumab was initiated alongside clobetasol 0.05% ointment. At follow-up, the patient reported persistent activity, receiving intramuscular triamcinolone acetonide and adjunctive therapies, including hydroxyzine, hydrocortisone 2.5% cream (for groin), and triamcinolone 0.1% ointment. By the second week of treatment, new plaques continued to appear daily without subjective improvement. Objective scoring with the Bullous Pemphigoid Disease Area Index was not obtained. This case illustrates the diagnostic and therapeutic challenges in managing ICI-induced BP and highlights the early course of dupilumab therapy, which had not yet produced clinical improvement at the time of last follow-up. Continued therapy was planned, and no adverse effects were reported.

2025-10-01·EUROPEAN JOURNAL OF PHARMACOLOGY

Safety profile of nivolumab-relatlimab in cancer patients: a living pharmacovigilance study of clinical trials and postmarketing data (version 1.0)

Review

作者: Wu, Chengmi ; Zhou, Jingyi ; Wu, Qian ; Jiang, Jie ; Yang, Ziwen ; Zhu, Jianhong ; Li, Sha ; Wu, Junyan

In 2022, the FDA approved nivolumab-relatlimab for the treatment of unresectable or metastatic melanoma. In the present study, we conducted a living pharmacovigilance study, integrating data from clinical trials and the FDA Adverse Event Reporting System (FAERS) database, to assess the safety profile of nivolumab-relatlimab. Treatment related adverse events (TRAEs) in trials of nivolumab-relatlimab available in electronic databases were systematically searched. The outcomes included were all-grade (grades 1-5) and high-grade (grades 3-5) TRAEs, considering both overall and individual aspects. Meta-analysis was conducted to calculate the incidence and risk ratio of TRAEs associated with nivolumab-relatlimab. Certainty of evidence was assessed using the GRADE system. Adverse events reports were extracted from the FAERS database, and a disproportionality analysis was carried out to estimate the safety signals of AEs associated with nivolumab-relatlimab. A total of 12 trials were included, the incidence of all-grade and high-grade TRAEs for nivolumab-relatlimab was 74.11 % and 38.05 %, respectively. Compared with nivolumab monotherapy, therapy with nivolumab-relatlimab was associated with a significantly increased risk of high-grade TRAEs, and some individual specified all-grade TRAEs, including hypothyroidism/thyroiditis, rash, diarrhea/colitis, hepatitis, adrenal insufficiency, hypophysitis, arthralgia and myalgia. Disproportionality analyses of FAERS pharmacovigilance data identified 39 positive signals, with 18 AEs not mentioned in the drug label. Nivolumab-relatlimab showed significantly higher reporting frequencies for 15 AEs than nivolumab monotherapy. Our study provides valuable insights into the potential safety profile of nivolumab-relatlimab, the results of this living study will be updated to incorporate new, robust evidence as it becomes available.

2025-01-11·Gastroenterology Report

Single-cell transcriptomic landscape indicates the potential role of immunotherapy in metastatic pancreatic angiosarcoma

Article

作者: Yang, Yizhen ; Chen, Luohai ; Zeng, Zhirong ; Peng, Sui ; Xie, Yubin ; Liu, Man ; Lin, Xiaoxuan ; Chen, Minhu ; Zhang, Ning

Abstract:

Background:

Pancreatic angiosarcoma is a rare and highly aggressive tumor originating from lymphatic or vascular endothelial cells, with poor prognosis and few effective treatments. In this study, we aimed to characterize the tumor ecosystem of metastatic pancreatic angiosarcoma, along with its potential treatment strategies.

Methods:

Single-cell RNA-sequencing and bioinformatics analysis were performed on samples obtained from one patient, including at total of 16,841 cells from pancreatic angiosarcoma liver metastasis and adjacent normal liver tissue.

Results:

Pancreatic angiosarcoma cells exhibited marked upregulation of nuclear factor kappa-B (NF-κB), hypoxia-inducible factor 1 (HIF-1), and myelocytomatosis oncogene (MYC) proto-oncogene signaling pathways, while presenting limited upregulation of actionable therapeutic targets except for cyclin-dependent kinase 4 (CDK4) and epidermal growth factor receptor. Several immune checkpoint genes, including cytotoxic T-lymphocyte-associated protein 4 (CTLA4), lymphocyte-activation gene 3 (LAG3), programmed cell death protein 1 (PDCD1), and cluster of differentiation 86 (CD86), were upregulated in tumor-infiltrating T cells, natural killer (NK) cells, and myeloid cells. Furthermore, intercellular interaction profiling demonstrated enhanced activity of the programmed death-ligand 1 (PD-L1) and CD86 signaling pathways within the tumor microenvironment. The gene-set scores of T/NK-cell exhaustion, regulatory T cell, and macrophage angiogenesis were significantly higher in tumor tissues compared with adjacent normal tissues. However, the phagocytosis scores of macrophages within the tumor-infiltrating region were significantly lower than those in the adjacent normal tissues.

Conclusions:

Our findings outlined an immunosuppressive and angiogenic tumor ecosystem in pancreatic angiosarcoma liver metastasis, suggesting that pancreatic angiosarcoma may be insensitive to most targeted therapies. Conversely, immunotherapies targeting LAG3, PD-L1, and CD86 (e.g. isatuximab, Opdualag, and abatacept) and anti-angiogenic agents may be therapeutically effective and worthy of subsequent exploration.

331

项与纳武利尤单抗/瑞拉利单抗相关的新闻（医药）

2026-08-23

·微信

一款双抗的失利，暴露了免疫双抗最难解的那道题

2026年8月17日，阿斯利康宣布终止 eVOLVE-Lung02[1]。这是 PD-1/CTLA-4 双特异性抗体 volrustomig（MEDI5752）联合化疗、头对头对比帕博利珠单抗联合化疗、一线治疗转移性非小细胞肺癌（mNSCLC）的全球 III 期试验：入组人群为 PD-L1 肿瘤细胞染色（TC）<50%，共 895 例、25 个国家[1,2] 。独立数据监查委员会按计划审查后的结论很直白：在主要分析人群——PD-L1 阴性（TC<1%）——volrustomig 联合化疗已不太可能达到无进展生存期（PFS）和总生存期（OS）的双主要终点[1]。次要终点所在的 ITT（PD-L1 TC<50%）结果、具体风险比和亚组数据，截至截稿日尚未公布。公告里还有一句容易被略过的话：联合用药的安全性与各组成药物既往研究中的特征一致，未发现新的安全信号[1]。换句话说，这次终止的直接公开原因是疗效增量在主要人群中看起来不够，而不是出现了新的毒性信号。在信息边界内，更准确的说法是「因无效性提前终止」，而不是已经读出一篇发表的头对头阴性 III 期。 PD-1 加 CTLA-4 的双重阻断，在联合用药层面早已被验证过。CheckMate-227 中，纳武利尤单抗联合伊匹木单抗对比化疗，PD-L1<1% 人群五年生存率 19% 对 7%[3]；POSEIDON 中，度伐利尤单抗联合限定疗程曲美木单抗再加化疗，对比单纯化疗的 OS 风险比为 0.77，并据此在美国获批[4,5]。这两项阳性试验的对照都是化疗，不是帕博利珠单抗联合化疗。KEYNOTE-189/407 之后，PD-1 加化疗已经是驱动基因阴性 mNSCLC 的一线标准，后来者要跨过的是另一道门槛。把这两个靶点装进同一个分子的 volrustomig，在同一适应症、同样联合化疗的条件下，没能在 PD-L1 TC<1% 人群对帕博利珠单抗联合化疗做出可预期的 PFS/OS 增量[1]。靶点组合没有变，CheckMate-227 是纳武利尤单抗每两周一次、伊匹木单抗每六周一次并可维持至两年[3]；POSEIDON 诱导期每三周一次、维持期度伐利尤单抗每四周一次，曲美木单抗只给五剂[4]。Volrustomig 则是 750 mg 每三周一次、两臂同步、最长 24 个月[1]。分子形态因此成为最值得追问的变量之一，但不是唯一变量：对照药、入组切点、CTLA-4 的剂量与时程、开放标签设计，都会写入结局。截至截稿日，全球获批上市的 PD-1/CTLA-4 双抗只有康方生物的卡度尼利单抗；根据医药魔方数据库查询，剔除复方类产品，全球范围内 PD-1/CTLA-4 相关的多特异性抗体管线共有44款之多。齐鲁制药的艾帕洛利单抗/托沃瑞利单抗（QL1706）以 MabPair 固定组合抗体的形式于 2024 年 9 月在中国获批，产品形态上更接近「两株抗体按比例共制剂」，而不是一条多肽上的双特异[6,7]。Volrustomig 曾是进度上最接近的全球挑战者。路透社引述阿斯利康口径，该分子整体峰值销售预期超过 50 亿美元，其中肺癌适应症约占两成[8]。它瞄准的肺癌一线，仍是免疫肿瘤领域体量最大的单一市场。种子选手在最宽的赛道上止步，才让这次失败超出单个项目，变成对「把两个检查点焊在同一个半衰期里」这条技术路线的一次压力测试。图源：医药魔方NextPharma全球新药数据库，点此试用结构—剂量—临床：一条需要收紧的推理链 Volrustomig 是双特异性人源化 IgG1，一价结合 PD-1，一价结合 CTLA-4，骨架采用 DuetMab，并对 Fc 做了降低效应功能的工程改造[9.10]。设计意图在五年前 Cancer Discovery 的论文里写得更细：利用 PD-1 端的高亲和力，让分子优先「坐」在 PD-1 阳性的活化 T 细胞表面，再在这些细胞上完成对 CTLA-4 的阻断，从而把 CTLA-4 的免疫激活尽量限制在肿瘤微环境内。 2022 年 ESMO 公布的 Ib/II 期数据里，1500 mg 联合化疗的疗效信号确实亮眼，但样本很小。1500 mg 组（n=20）客观缓解率 50.0%，对照帕博利珠单抗联合化疗（n=21）为 47.6%；中位缓解持续时间 20.5 个月（95% CI 4.1–NE）对 9.9 个月（95% CI 2.8–NE）；中位 PFS 15.1 个月对 8.9 个月[11]。毒性同样醒目：≥3/4 级治疗相关不良事件（TRAE）80.0% 对 61.9%，因不良事件停药 70.0% 对 28.6%，3/4 级丙氨酸转氨酶升高 30%、3/4 级天冬氨酸转氨酶升高 20%[11]。缓解持续时间几乎翻倍，但建立在二十例病人和极宽的置信区间上，不能单独支撑注册决策。首次人体试验的剂量爬坡从 2.25 mg 做到 2500 mg。按方案定义的 21 天剂量限制毒性（DLT）窗口，未达到经典 MTD；但 2000 mg 与 2500 mg 已出现 DLT，2500 mg 因窗口之外的累积毒性被判定不可耐受，免疫治疗初治扩展队列因此选在 2000 mg[10]。低于 1500 mg 的剂量耐受性明显好于 1500 mg 及以上。肾细胞癌早期队列 2000 mg 的客观缓解率在会议数据中被转述为约 37%，例数有限[12]。阿斯利康把后续扩展队列和 III 期剂量定在了 750 mg。 750 mg 的早期数据，必须把肺癌和肾癌、把 2022 年小样本和 2024 年更新分开写。ESMO 2022 肺癌 750 mg 联合化疗单臂队列（前 50 例、49 例可评估）ORR 为 40.8%，PD-L1 阴性（n=36）为 44.4%；G3/4 TRAE 50%，因 AE 停药 20%[11,13]。2024 年 WCLC 更新把肺癌 750 mg 队列扩到 140 例：非鳞状、PD-L1 TC<1% 的 ORR 42.3%（n=78），鳞状、PD-L1 TC<1% 的 ORR 50.0%（n=10）；G3/4 TRAE 75.7%（含铂类化疗贡献），治疗相关死亡 7 例[14]。「疗效尚可、毒性可控」只适合描述 2022 年那 50 例；放到 140 例更新里，毒性负担并不轻。III 期仍然选择 750 mg，说明开发团队接受了「用剂量换安全性、再拿安全性换可给药时间」的折中。 Volrustomig 是用共价键组装、不可拆分的单价单分子，两条功能臂共享同一条骨架、同一个 Fc、同一套清除途径。为了压制 CTLA-4 臂的毒性把总剂量从 1500 mg 砍到 750 mg 时，CTLA-4 与 PD-1 的名义剂量被同步砍半——分子内部没有机制允许「CTLA-4 少一点、PD-1 不变」。750 mg 下 CTLA-4 阻断被压到了临床增量以下，双抗在 PD-L1 阴性人群里退化成「并没有明显强过帕博利珠单抗」的 PD-1 阻断，再叠加化疗后做不出 OS/PFS。当然了，在 III 期详细数据公布前，这仍是假说。阿斯利康为volrustomig布下了四项 III 期。除终止的eVOLVE-Lung02 外，宫颈癌eVOLVE-Cervical（NCT06079671）、头颈鳞癌eVOLVE-HNSCC（NCT06129864）和间皮瘤eVOLVE-Meso（NCT06097728）按官方声明继续[1]。肺癌这一场的设计尤其讲究：入组限定 PD-L1 TC<50%，双主终点又聚焦 TC<1%——选择免疫治疗获益最不充分、未满足需求最高，但也最难做出增量的患者作为主战场。回过头看，这个人群设定既可以是机遇，也可以是陷阱。拿同类分子做对照：三条路线，三种命运在医药魔方数据库中对检索条件放宽，先看赛道全貌。选择PD（L）1×CTLA4作为靶点组合，筛选其中的双特异性的活跃管线，共15条；这 15 条里，百利天恒旗下 Systimmune 的 danvilostomig（SI-B003）已在 II 期，科伦博泰的 SKB337 还在 I 期，我们暂时挑选三个具备一定信息披露的分子进行初步分析。图源：医药魔方NextPharma全球新药数据库，点此试用 · 卡度尼利单抗（AK104）：把「微调」做到极致的工程榜样公开专利与结构论文描述它为由「靶向 PD-1 的免疫球蛋白 + 靶向 CTLA-4 的单链抗体」构成的对称四价分子；重链恒定区按 EU 编号 234/235/237 位点突变，降低与 FcγRIIIa 和 C1q 的亲和力，即效应功能沉默[15,16]。四价设计的意图，是在高抗原密度的肿瘤微环境里靠亲合力换局部滞留。卡度尼利 2022 年 6 月 29 日在中国获批复发或转移性宫颈癌二线及以上适应症，2024 年 9 月拓展至晚期胃或胃食管结合部腺癌一线，是全球首个获批的 PD-1/CTLA-4 双抗[6]。这个设计在临床上确实兑现了缩瘤能力。LungCadX 发表版纳入 PD-L1 阴性一线晚期 NSCLC 50 例（安全集）：卡度尼利联合含铂双药化疗的 ORR 66.0%，疾病控制率 100%，中位 PFS 9.7 个月，12 个月 PFS 率 42.1%[17]。≥3 级 TRAE 52.0%（任意级别 irAE 36.0%），≥3 级免疫相关不良事件 12.0%[17]。正在进行的 AK104-307（NCT05990127）是随机双盲 III 期，头对头替雷利珠单抗联合化疗，聚焦 PD-L1 TPS<1% 人群，计划入组 642 例[18]。图：AK104 专利 CN112300286A 来源：https://patents.google.com/patent/CN112300286A/zh 把时间轴拉长，隐患依然清晰。更早的 Ib/II 期给出了剂量与毒性的对照：联合安罗替尼、无化疗时，15mg/kg组≥3级TRAE 59.2%（n=49），10 mg/kg 组 25.0%（n=20）[19]。四价加 Fc 沉默削掉了外周免疫攻击的一部分锋芒，却没有改变一个事实：它仍然是不可拆分的刚性单分子，剂量上限依旧被 CTLA-4 相关毒性按在低位。替雷利珠单抗的 Fc 段经过工程改造，目的是尽量取消 FcγR 结合、避免巨噬细胞介导的 PD-1 阳性 T 细胞清除，而不是「把阻断效能做足」[20]。拿它当对照，AK104-307 真正要盯的是 OS 曲线后段和停药率。我们的看法是：单臂 II 期的高缓解率不能外推为 III 期一定赢下 PFS，更不能提前对 OS 下判；这个判断留给时间检验。 · Vudalimab（XmAb20717）：用亲和力差换安全性的实验 Xencor 的公开表述是：分子同时靶向 PD-1 与 CTLA-4，并优先结合双阳性 T 细胞；专利 WO2017218707A2 支持以亲和力差把 CTLA-4 阻断更多留在被 PD-1 捕获之后的局部[21,22]。这条路在安全性上有逻辑，代价是把疗效押在一个苛刻前提上——肿瘤微环境里要有足够多 PD-1 高表达、且与 CTLA-4 共表达的 T 细胞。前提不成立时，分子可能退化成一支更贵的 PD-1 单抗。它目前处于 II 期，临床读出还早。把机制完整性换成毒性空间，属于防御型创新；是否防御成功，仍取决于读出，而不是设计图。 · KN046（erfonrilimab）：跨细胞的代价专利 CN112399973A 描述为由两条多肽链形成的二聚体，每条链带 Fc 亚单位和免疫球蛋白单可变结构域（ISVD），其中至少一个结合 PD-L1、至少一个结合 CTLA-4[23]。它把锚点从 T 细胞上的 PD-1 换成肿瘤细胞和抗原递呈细胞上的 PD-L1，试图用跨细胞桥接把 CTLA-4 阻断拉到肿瘤局部。从结果看，这条路目前没有走通：KN046-303（一线胰腺癌）在 2024 年 5 月 28 日公告 OS 未达预设统计终点[24]；KN046-301（一线鳞状 NSCLC）在 2023 年 5 月 19 日公告因 OS 暂未达到统计学显著性差异而未能揭盲[25]。表：有公开信息的 PD-1/PD-L1×CTLA-4 代表分子分子原研靶点价态 / 形态阶段 Volrustomig MEDI5752AstraZenecaPD-1×CTLA-41+1 单价 IgG 样 DuetMab，Fc 效应功能降低III 期肺癌试验已终止卡度尼利 AK104康方生物PD-1×CTLA-4对称四价 Fc-null、高亲合力已批准上市 QL1706艾帕洛利/托沃瑞利齐鲁制药PD-1 + CTLA-4复方MabPair 共表达两株抗体比例可调，非单分子双抗已批准上市 Vudalimab XmAb20717XencorPD-1×CTLA-41+1 异二聚体优先结合双阳性 T 细胞II 期 Lorigerlimab MGD019MacroGenicsPD-1×CTLA-4DART/diabodyII 期 Danvilostomig SI-B003SystimmunePD-1×CTLA-4四价（公司公开表述）II 期 Erfonrilimab KN046康宁杰瑞PD-L1×CTLA-4ISVD-Fc 二聚体 PD-L1 反式桥接III 期已有阴性读出 SKB337科伦博泰PD-L1×CTLA-4公开结构信息有限I 期注：QL1706 列入是为了对照「共制剂解耦」，不把它算作经典双抗联用方案给出的是剂量解耦，并不都是时间解耦如果说从结构到临床结果的推理还需要一点想象力，那么两项经典联用 III 期的给药设计提供了更硬的证据——但必须把「剂量解耦」和「时间解耦」分开。 CheckMate-227 里，纳武利尤单抗 3 mg/kg 每两周一次，伊匹木单抗 1 mg/kg 每六周一次，两药都可维持到疾病进展或最长两年[3]。这是低剂量、低频次的 CTLA-4，不是短疗程。POSEIDON 里，度伐利尤单抗 1500 mg 联合化疗按诱导节奏给药，曲美木单抗 75 mg 在化疗的四个周期内给予，并在第 16 周再给第五剂，之后进入度伐利尤单抗维持；方案允许进展后有限再诱导，因此也不是绝对意义上的「彻底停药」[4]。CheckMate-9LA 则把双免与两程化疗搭配，用最短程的细胞毒性换早期疾病控制，同样拿到了 OS 获益[27]。把三种安排并排放在一起：伊匹木单抗 1 mg/kg 每六周一次、可持续；曲美木单抗 75 mg 以五剂为计划疗程；volrustomig 750 mg 每三周一次两臂同步直至 24 个月。全球开发团队用十年试错换来的共识，更准确的表述是：CTLA-4 需要与 PD-1 解耦——至少解耦剂量和频率，部分方案进一步解耦疗程。想把 CTLA-4 的毒性预算用完、又让 PD-1 长期占位，就不能让两臂同涨同落。所谓「临床解耦」，在联合用药层面已经完成了一半（剂量），只在部分方案里完成了另一半（时间）。刚性单分子双抗默认两半都做不到。对照之下，volrustomig 这类分子做的事情，等于把一个需要长期高占用的靶点（PD-1）和一个治疗指数更窄的靶点（CTLA-4）用肽键锁进同一个半衰期里。风险被预言过；eVOLVE-Lung02 的无效性终止，是这条预言在最高门槛适应症上的一次压力测试，但还不是对整条路线的终审判决。把尺子伸向整条 IO 赛道 · 4-1BB：高毒靶点必须解耦，条件激活是当前主流解 4-1BB 是强免疫激动靶点。BMS 第一代激动剂单抗 urelumab 在 ≥1.0 mg/kg 出现显著肝毒性（AST 升高约 27%，3/4 级约 14%–17%），2008 年 12 月因两例肝毒性相关死亡在全球暂停入组，2012 年才以更低剂量重启[28,29]。这条赛道在医药魔方里能数出 93 条活跃双抗，除上述三家外，此后在研的 PD-(L)1×4-1BB 双抗——如 Genmab/BioNTech 的 acasunlimab（GEN1046）、普米斯 PM1003、百奥泰 BAT7111——普遍采用空间条件性交联：对 PD-(L)1 相对高亲和、对 4-1BB 相对弱亲和，让分子在血液里尽量保持沉默，只有被高表达 PD-(L)1 的肿瘤大量捕获后，才把周围 T 细胞的 4-1BB 拉拢交联。这类分子最终是「加强版 PD-(L)1 单抗」还是真正的双功能药，取决于肿瘤微环境配不配合，III 期之前不宜下结论。 · LAG-3 与 TIGIT：温和靶点必须回答「双抗比联用多带来了什么」 LAG-3 和 TIGIT 属于安全性相对温和的检查点，不存在 CTLA-4、4-1BB 那种典型的剂量限制性毒性，双抗也就谈不上「毒性解耦」的红利。单抗联用的标杆已经立着：Opdualag（纳武利尤单抗 480 mg + relatlimab 160 mg 固定剂量复方）2022 年 3 月获 FDA 批准用于不可切除或转移性黑色素瘤，依据 RELATIVITY-047——联合组中位 PFS 10.1 个月、纳武利尤单抗单药 4.6 个月，HR 0.75，3/4 级药物相关不良事件 18.9% 对 9.7%[30,31]。既然输液袋里混一混就能拿到这样的结果，1:1 刚性双抗就必须回答：两种受体在 T 细胞膜上的距离未必匹配，双特异结合的效率可能并不高于两株游离单抗各自作业，那么双抗到底多带来了什么？TIGIT 单抗这边，罗氏 tiragolumab 联合阿替利珠单抗在 SKYSCRAPER 系列 III 期中的表现反复，始终没有形成一致的 OS 获益。医药魔方里 PD-1/PD-L1 × LAG-3 与 × TIGIT 的管线加起来接近五十条，PD-1×TIGIT 双抗能否在 III 期里显著优于单抗联用，才是真正的大考。 · TGF-β 的反面与 VEGF 的正面：几何决定的是天花板，不是命运默克的 M7824（bintrafusp alfa）把 PD-L1 抗体和 TGF-β 受体陷阱装在同一个分子上，一度被视为明星。结局现在很清楚：一线 PD-1 高表达 NSCLC 的 III 期 INTR@PID Lung 037（n=304）里，M7824 组中位 PFS 7.0 个月、对照帕博利珠单抗 11.1 个月，HR 1.23，试验在 2021 年 1 月因无效性提前终止；胆道癌 III 期随后终止，Merck 与 GSK 的全球联盟在 2021 年 9 月画上句号[32,33]。失败的主因是疗效，而非新的毒性信号；但它的毒性确实有特征——1200 mg 每两周一次剂量下，任意级别出血 34.8%、≥3 级 8.6%[34]。TGF-β 维持着全身血管内皮的完整性，一个游离的细胞因子陷阱不管接在哪种抗体上，都无法只吸附肿瘤里的 TGF-β；为了控制系统性毒性去降剂量，PD-L1 的阻断强度又可能不够。同样是跨界组合，康方生物的依沃西单抗（AK112，PD-1×VEGF）给出了正面读出。它的几何结构更宽容：PD-1 在 T 细胞膜上，VEGF 是游离因子，结合后者不需要把两种细胞拉到一起；VEGF 相关毒性（高血压、蛋白尿）与 PD-1 相关毒性（自身免疫性炎症）作用在不同器官系统上，两臂的毒性预算不在同一本账上。HARMONi-2（n=398，中国多中心）中，依沃西 20 mg/kg 单药对比帕博利珠单抗 200 mg 单药一线治疗 PD-L1 阳性 NSCLC，中位 PFS 11.14 对 5.82 个月，HR 0.51（95% CI 0.38–0.69）[35,36]。≥3 级蛋白尿 3.1% 对 0；≥3 级 TRAE 29.4% 对 15.6%，严重 TRAE 20.8% 对 16.1%[35,36]。它是第一个在随机 III 期、以 PFS 为终点、在中国 PD-L1 阳性人群里击败帕博利珠单抗单药的药物。OS 在该分析时不成熟，最终成色仍需等待。总结回到产业层面。阿斯利康在公告里留了余地：eVOLVE-Lung02 的终止不影响 volrustomig 其他 III 期，宫颈癌、头颈鳞癌和间皮瘤的注册研究按计划推进[1]。这个安排本身也说明了问题——在 PD-1 加化疗已是标准、且已有双免获批的肺癌一线，后来者要跨过的门槛最高；在免疫治疗渗透更浅的瘤种，同样的分子或许仍有空间。栏目介绍《医药深思考》栏目由医药魔方研究中心打造的一档行业深度解读专栏，每周精选一个热点事件或热门赛道，做结构化拆解与独立判断。文章为公开阅读，更深度的闭门研讨可报名参加「医药深思考」系列直播。 - 上下滑动查看参考资料 - 1. AstraZeneca eVOLVE-Lung02 终止公告（Investegate，2026-08-17）: https://www.investegate.co.uk/announcement/rns/astrazeneca--azn/update-on-evolve-lung02-phase-iii-trial/9724094 2. 医药魔方：阿斯利康终止 PD-1/CTLA-4 双抗治疗肺癌III期临床（2026-08-17）: https://www.163.com/dy/article/L4HRTB1T0534Q32Z.html 3. Tran B, et al. Safety, PK, PD, and Preliminary Efficacy from a FIH Study of Volrustomig. Clin Cancer Res 2026;32:2850-64: https://aacrjournals.org/clincancerres/article-split/32/14/2850/786647/Safety-Pharmacokinetics-Pharmacodynamics-and 4. Dovedi SJ, et al. Design and Efficacy of a Monovalent Bispecific PD-1/CTLA4 Antibody. Cancer Discov 2021;11(5):1100: https://aacrjournals.org/cancerdiscovery/article/11/5/1100/666290 5. 专利 CN109152835B（Volrustomig 核心序列，授权）: https://patents.google.com/patent/CN109152835B/zh 6. ESMO 2022：MEDI5752 或 pembro + CP 一线 NSCLC Ib/II 期（AZ 资源页）: https://oncologypro.esmo.org/meeting-resources/esmo-congress/medi5752-or-pembrolizumab-p-plus-carboplatin-pemetrexed-cp-in-treatment-naive-1l-non-small-cell-lung-cancer-nsclc-a-phase-ib-ii-trial 7. 行业复盘：三期折戟、AZ 豪赌落空（1500mg/750mg 组安全性数据转述）: http://m.toutiao.com/group/7675925900386435590/ 8. 专利 CN106967172B（AK104 核心序列，授权）: https://patents.google.com/patent/CN106967172B/zh 9. 专利 CN112300286A（AK104 序列与 Fc 234/235/237 突变）: https://patents.google.com/patent/CN112300286A/zh 10. AACR 2025 Abstract 3206（LungCadX 摘要版，n=56）: https://aacrjournals.org/cancerres/article/85/8_Supplement_1/3206/760844/Abstract-3206-Cadonilimabplus-chemotherapy-as 11. LungCadX 研究发表版解读（Nature Communications，n=50，ORR 66.0%、mPFS 9.7 个月）: http://m.toutiao.com/group/7670488134928400937/ 12. Chen B, et al. Cadonilimab plus anlotinib in advanced NSCLC. Br J Cancer 2024;130:450-456: https://pmc.ncbi.nlm.nih.gov/articles/PMC10844309/pdf/41416_2023_Article_2519.pdf 13. ClinicalTrials.gov NCT05990127（AK104-307）: https://clinicaltrials.gov/study/NCT05990127 14. 专利 WO2017218707A2（Vudalimab 核心序列，Xencor）: https://patents.google.com/patent/WO2017218707A2/en 15. 专利 CN112399973A（KN046 序列，授权）: https://patents.google.com/patent/CN112399973A/zh 16. Alphamab KN046-303（胰腺癌III期 OS 未达标，2024-05）: https://flcube.com/?p=3389 17. Zhao Y, et al. FIH phase I/Ib study of QL1706. J Hematol Oncol 2023;16:50: https://pmc.ncbi.nlm.nih.gov/articles/PMC10169367/ 18. Ma Y, et al. Updated efficacy and biomarkers of QL1706. Cell Rep Med 2025;6:102396: https://pmc.ncbi.nlm.nih.gov/articles/PMC12629821/pdf/main.pdf 19. ASCO 2023 TPS9139（QL1706+CT vs tislelizumab+CT III期设计，NCT05690945）: https://ascopubs.org/doi/pdfdirect/10.1200/JCO.2023.41.16_suppl.TPS9139 20. CheckMate-227 五年生存结果. J Clin Oncol（JCO.22.01503）: https://ascopubs.org/doi/pdfdirect/10.1200/JCO.22.01503 21. CheckMate-227 四年更新（ASCO abstr 9016）: https://www.asco.org/abstracts-presentations/196847/poster 22. POSEIDON 主结果. J Clin Oncol（JCO.22.00975）: https://ascopubs.org/doi/pdfdirect/10.1200/jco.22.00975 23. AZ：Imfinzi+Imjudo+化疗美国获批公告（2022-11-11）: https://www.astrazeneca-us.com/media/press-releases/2022/imfinzi-and-imjudo-with-chemotherapy-approved-in-the-us-for-patients-with-metastatic-non-small-cell-lung-cancer-11112022.html 24. 专利 US10954301B2（Lorigerlimab 序列，授权）: https://patents.google.com/patent/US10954301B2/en 25. Khushalani NI, et al. Final results of urelumab. J Immunother Cancer 2024;12:e007364: https://pmc.ncbi.nlm.nih.gov/articles/PMC10921538/ 26. Urelumab 条目（2008 年两例肝毒性死亡后全球暂停）: https://www.creativebiolabs.net/urelumab-overview.htm 27. M7824 INTR@PID Lung 037III期结果（PubMed 37597750）: https://pubmed.ncbi.nlm.nih.gov/37597750/ 28. Merck KGaA INTR@PID 项目更新公告（含 Lung 037 终止）: https://www.prnewswire.com/news-releases/merck-kgaa-darmstadt-germany-announces-update-on-the-intrpid-clinical-program-including-lung-037-study-301211771.html 29. Vugmeyster Y, et al. Bleeding risk management for bintrafusp alfa. Cancer Chemother Pharmacol 2022;90:369-379: https://pmc.ncbi.nlm.nih.gov/articles/PMC9474582/ 30. Xiong A, et al. Ivonescimab vs pembrolizumab（HARMONi-2）. Lancet 2025;405:839-849: https://pubmed.ncbi.nlm.nih.gov/40057343/ 31. Summit：HARMONi-2 主分析公告（2024-09-08）: https://www.businesswire.com/news/home/20240908828765/en/Ivonescimab-Monotherapy-Reduced-the-Risk-of-Disease-Progression-or-Death-by-49-Compared-to-Pembrolizumab-Monotherapy-in-First-Line-Treatment-of-Patients-with-PD-L1-Positive-Advanced-NSCLC-in-China 32. BMS：Opdualag FDA 获批公告（2022-03-18）: https://news.bms.com/news/details/2022/U.S.-Food-and-Drug-Administration-Approves-First-LAG-3-Blocking-Antibody-Combination-Opdualag-nivolumab-and-relatlimab-rmbw-as-Treatment-for-Patients-with-Unresectable-or-Metastatic-Melanoma/default.aspx 33. FDA Drug Trials Snapshot: Opdualag: https://www.fda.gov/drugs/drug-approvals-and-databases/drug-trials-snapshot-opdualag 34. 专利 WO2026067748A1（BAT7111，PD-1×4-1BB）: https://patents.google.com/patent/WO2026067748A1/en 35. Bose CK, et al. Bispecific immunotherapy MEDI5752 and cervical cancer. J Gynecol Oncol 2024;35:e82: https://pmc.ncbi.nlm.nih.gov/articles/PMC11262897/1. AstraZeneca eVOLVE-Lung02 终止公告（Investegate，2026-08-17）: https://www.investegate.co.uk/announcement/rns/astrazeneca--azn/update-on-evolve-lung02-phase-iii-trial/9724094 2. 医药魔方：阿斯利康终止 PD-1/CTLA-4 双抗治疗肺癌III期临床（2026-08-17）: https://www.163.com/dy/article/L4HRTB1T0534Q32Z.html 3. Tran B, et al. Safety, PK, PD, and Preliminary Efficacy from a FIH Study of Volrustomig. Clin Cancer Res 2026;32:2850-64: https://aacrjournals.org/clincancerres/article-split/32/14/2850/786647/Safety-Pharmacokinetics-Pharmacodynamics-and 4. Dovedi SJ, et al. Design and Efficacy of a Monovalent Bispecific PD-1/CTLA4 Antibody. Cancer Discov 2021;11(5):1100: https://aacrjournals.org/cancerdiscovery/article/11/5/1100/666290 5. 专利 CN109152835B（Volrustomig 核心序列，授权）: https://patents.google.com/patent/CN109152835B/zh 6. ESMO 2022：MEDI5752 或 pembro + CP 一线 NSCLC Ib/II 期（AZ 资源页）: https://oncologypro.esmo.org/meeting-resources/esmo-congress/medi5752-or-pembrolizumab-p-plus-carboplatin-pemetrexed-cp-in-treatment-naive-1l-non-small-cell-lung-cancer-nsclc-a-phase-ib-ii-trial 7. 行业复盘：三期折戟、AZ 豪赌落空（1500mg/750mg 组安全性数据转述）: http://m.toutiao.com/group/7675925900386435590/ 8. 专利 CN106967172B（AK104 核心序列，授权）: https://patents.google.com/patent/CN106967172B/zh 9. 专利 CN112300286A（AK104 序列与 Fc 234/235/237 突变）: https://patents.google.com/patent/CN112300286A/zh 10. AACR 2025 Abstract 3206（LungCadX 摘要版，n=56）: https://aacrjournals.org/cancerres/article/85/8_Supplement_1/3206/760844/Abstract-3206-Cadonilimabplus-chemotherapy-as 11. LungCadX 研究发表版解读（Nature Communications，n=50，ORR 66.0%、mPFS 9.7 个月）: http://m.toutiao.com/group/7670488134928400937/ 12. Chen B, et al. Cadonilimab plus anlotinib in advanced NSCLC. Br J Cancer 2024;130:450-456: https://pmc.ncbi.nlm.nih.gov/articles/PMC10844309/pdf/41416_2023_Article_2519.pdf 13. ClinicalTrials.gov NCT05990127（AK104-307）: https://clinicaltrials.gov/study/NCT05990127 14. 专利 WO2017218707A2（Vudalimab 核心序列，Xencor）: https://patents.google.com/patent/WO2017218707A2/en 15. 专利 CN112399973A（KN046 序列，授权）: https://patents.google.com/patent/CN112399973A/zh 16. Alphamab KN046-303（胰腺癌III期 OS 未达标，2024-05）: https://flcube.com/?p=3389 17. Zhao Y, et al. FIH phase I/Ib study of QL1706. J Hematol Oncol 2023;16:50: https://pmc.ncbi.nlm.nih.gov/articles/PMC10169367/ 18. Ma Y, et al. Updated efficacy and biomarkers of QL1706. Cell Rep Med 2025;6:102396: https://pmc.ncbi.nlm.nih.gov/articles/PMC12629821/pdf/main.pdf 19. ASCO 2023 TPS9139（QL1706+CT vs tislelizumab+CT III期设计，NCT05690945）: https://ascopubs.org/doi/pdfdirect/10.1200/JCO.2023.41.16_suppl.TPS9139 20. CheckMate-227 五年生存结果. J Clin Oncol（JCO.22.01503）: https://ascopubs.org/doi/pdfdirect/10.1200/JCO.22.01503 21. CheckMate-227 四年更新（ASCO abstr 9016）: https://www.asco.org/abstracts-presentations/196847/poster 22. POSEIDON 主结果. J Clin Oncol（JCO.22.00975）: https://ascopubs.org/doi/pdfdirect/10.1200/jco.22.00975 23. AZ：Imfinzi+Imjudo+化疗美国获批公告（2022-11-11）: https://www.astrazeneca-us.com/media/press-releases/2022/imfinzi-and-imjudo-with-chemotherapy-approved-in-the-us-for-patients-with-metastatic-non-small-cell-lung-cancer-11112022.html 24. 专利 US10954301B2（Lorigerlimab 序列，授权）: https://patents.google.com/patent/US10954301B2/en 25. Khushalani NI, et al. Final results of urelumab. J Immunother Cancer 2024;12:e007364: https://pmc.ncbi.nlm.nih.gov/articles/PMC10921538/ 26. Urelumab 条目（2008 年两例肝毒性死亡后全球暂停）: https://www.creativebiolabs.net/urelumab-overview.htm 27. M7824 INTR@PID Lung 037III期结果（PubMed 37597750）: https://pubmed.ncbi.nlm.nih.gov/37597750/ 28. Merck KGaA INTR@PID 项目更新公告（含 Lung 037 终止）: https://www.prnewswire.com/news-releases/merck-kgaa-darmstadt-germany-announces-update-on-the-intrpid-clinical-program-including-lung-037-study-301211771.html 29. Vugmeyster Y, et al. Bleeding risk management for bintrafusp alfa. Cancer Chemother Pharmacol 2022;90:369-379: https://pmc.ncbi.nlm.nih.gov/articles/PMC9474582/ 30. Xiong A, et al. Ivonescimab vs pembrolizumab（HARMONi-2）. Lancet 2025;405:839-849: https://pubmed.ncbi.nlm.nih.gov/40057343/ 31. Summit：HARMONi-2 主分析公告（2024-09-08）: https://www.businesswire.com/news/home/20240908828765/en/Ivonescimab-Monotherapy-Reduced-the-Risk-of-Disease-Progression-or-Death-by-49-Compared-to-Pembrolizumab-Monotherapy-in-First-Line-Treatment-of-Patients-with-PD-L1-Positive-Advanced-NSCLC-in-China 32. BMS：Opdualag FDA 获批公告（2022-03-18）: https://news.bms.com/news/details/2022/U.S.-Food-and-Drug-Administration-Approves-First-LAG-3-Blocking-Antibody-Combination-Opdualag-nivolumab-and-relatlimab-rmbw-as-Treatment-for-Patients-with-Unresectable-or-Metastatic-Melanoma/default.aspx 33. FDA Drug Trials Snapshot: Opdualag: https://www.fda.gov/drugs/drug-approvals-and-databases/drug-trials-snapshot-opdualag 34. 专利 WO2026067748A1（BAT7111，PD-1×4-1BB）: https://patents.google.com/patent/WO2026067748A1/en 35. Bose CK, et al. Bispecific immunotherapy MEDI5752 and cervical cancer. J Gynecol Oncol 2024;35:e82: https://pmc.ncbi.nlm.nih.gov/articles/PMC11262897/ Copyright © 2026 PHARMCUBE. All Rights Reserved.免责申明：本微信文章中的信息仅供一般参考之用，不可直接作为决策内容，医药魔方不对任何主体因使用本文内容而导致的任何损失承担责任。

2026-08-15

·研报客

20260811-东吴证券-医药生物行业点评报告_百时美施贵宝2026Q2_Eliquis驱动业绩超预期_milvexian等关

✓ 研报客AI助手 · 智能报告解读百时美施贵宝 2026Q2 业绩与研发进展总结核心内容概述 2026年第二季度，百时美施贵宝（BMS）披露了其财务表现及研发进展，整体业绩超出市场预期。公司总营收达129.7亿美元，同比增长5.7%；非GAAP每股收益为2.04美元。成长组合收入75.6亿美元，同比增长15%，成为推动公司增长的核心力量。公司同时上调了2026年全年营收及非GAAP EPS指引，显示出对市场前景的信心。主要观点 Eliquis 表现强劲：作为公司核心产品，Eliquis 在2026Q2 销售额达44.8亿美元，同比增长22%，占据美国新开具抗凝治疗处方的80%市场份额。成长组合驱动增长：成长组合中的多款药物表现亮眼，如Reblozyl、Breyanzi、Camzyos、Opdualag、Krazati及Qvantig等，均实现显著增长，显示出公司在创新药物领域的持续竞争力。 PD-1 皮下剂型放量：Qvantig作为PD-1单抗皮下剂型，在2026Q2销售额达2.61亿美元，同比增长770%，2026H1销售额达4.24亿美元，同比增长1016%，表明该剂型市场接受度迅速提升。研发进展后移：三项关键III期临床试验的揭盲时间集体后移，包括milvexian、Cobenfy及admliparant，预计分别在2027Q1、2027年初及2027年完成顶线数据。这一调整可能影响产品上市节奏，但公司仍表示将继续推进相关研究。收购与平台拓展：2026年7月，公司收购Firefly Bio，获得基于降解技术的精准ADC平台，为未来药物研发提供更多技术支撑。关键信息财务表现总营收：2026Q2为129.7亿美元（+5.7%），2026H1为244.62亿美元（+4%）。成长组合：2026Q2为75.6亿美元（+15%），成为主要增长引擎。增长阶段产品：2026H1销售额为137.87亿美元（+13%）。成熟产品：2026H1销售额为106.99亿美元（-5%）。全年指引：营收由460-475亿美元上调至490-500亿美元；非GAAP EPS由6.05-6.35美元上调至6.75-7.00美元。股票回购：剩余股票回购授权约50亿美元。研发进展 milvexian：口服因子XIa抑制剂，作为Eliquis的潜在接班人，主要终点为卒中或非中枢神经系统体循环栓塞非劣效，预计2027Q1揭盲。 Cobenfy：精神分裂症口服新药，适应症拓展至阿尔茨海默病相关精神病，ADEPT项目顶线数据推迟至2027年初。 admliparant：口服LPA1拮抗剂，同步验证60mg与120mg剂量，主要终点为52周FVC绝对变化。 Qvantig：PD-1单抗皮下剂型，市场接受度快速提升，2026H1销售额达4.24亿美元。投资建议关注抗凝药物升级：Eliquis在抗凝领域仍具主导地位，milvexian作为下一代抗凝药物，公司布局显示市场存在代际升级需求。建议关注国内布局FXIa/FXI靶点的创新药企，如恒瑞医药、瑞博生物。 CNS 新机制药物价值：Cobenfy作为70年来首个全新机制的精神分裂症药物，向阿尔茨海默病相关精神病拓展，凸显CNS新机制药物的稀缺价值。建议关注拥有该药国内权益的再鼎医药。 PD-1 皮下剂型趋势：Opdivo皮下剂型销售放量，PD-1向皮下及长效剂型迭代趋势明显，建议关注国内具备相关开发能力的头部企业。风险提示研发进展不及预期；商业化推进不及预期；海外审批或收益不达预期；国际地缘政治风险。总结百时美施贵宝在2026Q2业绩表现超预期，主要得益于核心产品Eliquis的持续增长及成长组合中多款创新药物的强劲销售。尽管部分成熟产品受仿制药冲击出现下滑，但公司通过调整研发计划及收购技术平台，积极布局下一代抗凝药物及CNS领域创新药物，展现出强大的研发与商业化能力。投资者可关注国内相关创新药企的布局进展，同时需注意潜在的研发与市场风险。 ▸ 报告内容 ▸ 点击下方卡片 · 免费获取报告源文件研报客 YANBAOKE · 智能研报聚合平台整合全球5000+研究机构 · 汇集500万+专业报告 · 全行业深度覆盖连接世界顶级智库 · 获取百万中英研报 · 一站式研究解决方案 ✓ 主要服务 📂 报告库：跨行业覆盖 · 智能搜索 · 全文定位 🔄 语言处理：多语种互译 · 原版样式保留 🤝 智能助手：文档问答 · 深度解析 · 专业应答 🔕 订阅推送：关键词订阅 · 实时更新通知 💻 多终端：PC端 · 移动APP · 微信小程序 ✓ 智能特色 🔎 意图识别：精准理解需求 · 高效匹配结果 📡 信息融合：多源交叉验证 · 综合分析输出 🧩 深度理解：超越字面 · 把握语境文化内涵 📐 领域适配：科技 · 商务 · 学术 · 专业术语 💭 对话记忆：上下文连贯 · 多轮交互支持 📖 文档精通：专业研报解读 · 结构化分析 📡 实时更新：最新资讯获取 · 主动推送 ✓ 应用领域 💰 投资决策：券商报告 · 市场研判 · 策略制定 📊 商业洞察：行业扫描 · 趋势追踪 · 竞品分析 🏗️ 产业分析：深度研究 · 价值链梳理 🔮 前瞻研判：发展走向 · 技术路径 · 政策风向 ✓ 产品入口 🌐 PC网页：pc.yanbaoke.cn 📲 移动应用：应用商店搜索「研报客」 💻 客户端：pc.yanbaoke.cn/pc2.html 🗲 微信小程序：搜索「研报客」 ▸ 多格式转换 · 文本提取 · 便捷下载分享多端数据同步 · 随时随地研读 AI生成内容 · 仅供参考

临床3期并购财报抗体药物偶联物

2026-08-05

·BioSpace

Seres Therapeutics Reports Second Quarter 2026 Financial Results and Provides Business Updates, Including Further Action to Reduce Ongoing Facilities Costs

Recently announced 80% of SER-155 recipients achieved immunosuppressive-free clinical response at day 15 for immune checkpoint inhibitor-related enterocolitis (irEC) in the investigator-sponsored trial (IST) conducted by Memorial Sloan Kettering Cancer Center (MSK) IST data support SER-155 as a potential treatment for irEC that may allow patients to continue cancer therapy; Company evaluating irEC clinical development strategy in consultation with KOLs Seres engaging potential partners, seeking capital to advance its SER-155 programs, including for the prevention of bloodstream infections in patients undergoing allo-HCT and those experiencing irEC Seres announces agreement to exit additional leased space early, further reducing ongoing facility-related cash costs, which follows announcement of balance sheet strengthening and facilities cost reduction transactions in June 2026 ezstandalone.cmd.push(function () { ezstandalone.showAds(131); }); CAMBRIDGE, Mass., Aug. 05, 2026 (GLOBE NEWSWIRE) -- Seres Therapeutics, Inc. (Nasdaq: MCRB), (Seres or the Company), a leading live biotherapeutics company, today reported second quarter 2026 financial results and provided business updates. "We are very pleased with the recent progress at Seres, including the positive topline data from the investigator-sponsored trial of SER-155 in irEC conducted by MSK, announced last month," said Richard Kender, Executive Chairman and Interim Chief Executive Officer of Seres. "The study demonstrated that 80% of participants achieved an immunosuppressive-free clinical response at day 15, and the accompanying pharmacology data reinforced that our live biotherapeutic operated as designed, including by repairing the mucosal epithelial barrier. SER-155 to treat irEC, a frequent and often severe side effect of widely used immune checkpoint inhibitor (ICI) cancer treatment, represents a meaningful therapeutic and commercial opportunity, as many patients who experience irEC are required to halt their ICI therapy and begin immunosuppressive corticosteroid treatment. We are engaging potential partners, including companies with ICI franchises, as we evaluate the clinical development pathway in this indication and consider sources of financing. In parallel, we continue to pursue partnerships and other financing sources to support development of SER-155 in allo-HCT, and to advance our broader inflammatory and immune portfolio, including SER-603 for inflammatory bowel disease." Marella Thorell, Chief Financial Officer of Seres, added, "Terminating our Sidney Street lease will substantially reduce our future lease obligations and will further lower our ongoing annual fixed costs beginning in 2027. Together with the lease restructuring we announced in June, this transaction reflects our continued focus on rigorous financial discipline, while we maintain the operational infrastructure needed to advance our live biotherapeutic pipeline, including our Phase 2-ready SER-155 program in allo-HCT." Recent Highlights SER-155 in immune checkpoint inhibitor-related enterocolitis (irEC) In July, Seres announced positive topline results from the IST of SER-155 in irEC (NCT06801067) conducted at MSK. The open-label study evaluated SER-155 in 15 participants with moderate-to-severe (Grade 2-3) irEC who were naïve to immunosuppressive therapy. irEC is among the most frequent and severe immune-related adverse reactions in recipients of ICI therapy and, at the moderate-to-severe grade, affects approximately 25% of ICI recipients in the US. In the study, 12 of 15 participants (80%) achieved an immunosuppressive-free clinical response at day 15, the primary efficacy endpoint, defined as at least a 1-grade improvement in diarrhea symptoms without immunosuppressive therapy. SER-155 was generally well tolerated with no safety concerns identified and no serious adverse events assessed as related to SER-155. Participants in the study were on a wide range of ICI types, including PD-1 inhibitors (Keytruda®, Opdivo®, Zynyz®), PD-L1 inhibitors (Imfinzi®, Bavencio®), CTLA-4 inhibitors (Yervoy®, Imjudo®), LAG-3 inhibitor (Opdualag®), and combinations thereof. The promising study results support continued development of SER-155 to treat irEC and the Company is engaging potential partners, including companies with ICI franchises, as it evaluates next steps for the development of SER-155 in irEC. Broader pipeline and portfolio SER-155 remains Phase 2 ready for the prevention of bloodstream infections in patients undergoing allogeneic hematopoietic stem cell transplant (allo-HCT) for the treatment of blood cancer. SER-155 has received Breakthrough Therapy and Fast Track designations for this indication. Efforts to secure funding to advance clinical development for this program continue. The Company continues to advance IND-enabling activities for SER-603, in development for inflammatory bowel disease, and is engaging potential collaborators to support the clinical advancement of this program as a mono and/or combination therapy. Seres continues to progress development of SER-428, an investigational oral liquid formulation based on SER-155 strains supported by a grant from CARB-X (Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator), for dosing in patients who cannot take oral capsules. Seres is designing a Phase 1b open-label trial, in collaboration with Dr. Dan Freedberg at Columbia University, to evaluate SER-428 in medical ICU patients at high risk of infection. Corporate Updates Seres completed the below transactions that will collectively strengthen the Company’s balance sheet and reduce ongoing annual facility cash costs. On July 31, Seres entered into an agreement to terminate the lease for its facility at 200 Sidney Street in Cambridge, MA. This early termination eliminates the Company's remaining obligations under the lease as of December 31, 2026 in exchange for certain consideration and will further significantly reduce ongoing facility-related cash costs beginning in 2027. Additional details regarding the agreement are included in the Company's Report on Form 8-K, which was filed with the Securities and Exchange Commission on August 4, 2026. The accounting for this transaction will be reported in the Company’s third quarter 2026 results. In June, Seres restructured the lease for its facility at 101 CambridgePark Drive in Cambridge, MA, reducing its leased space, rental rate and related operating expenses. The restructured 10-year lease is expected to materially reduce the Company's ongoing annual facility-related cash costs and long-term lease obligations. In June, Seres entered into an amendment to its asset purchase agreement with Nestlé Health Science (Nestlé) under which Nestlé will pay Seres an aggregate $25 million (the Milestone Termination Payment), in two equal installments of $12.5 million on July 1, 2026 (which was received) and $12.5 million which is expected to be received on October 1, 2026, to buy out potential future VOWST net sales-based milestones. Seres sold the VOWST business to Nestlé Health Science in 2024. Second Quarter 2026 Financial Results Net income was $4.6 million for the second quarter of 2026, compared to a net loss of $19.9 million for the same period in 2025. The difference is primarily due to a $25 million Gain on Sale of the VOWST Business recognized in the second quarter of 2026 arising from the Milestone Termination Payment due from Nestlé. Research and development expenses were $9.1 million for the second quarter of 2026, compared with $12.9 million for the same period in 2025, reflecting lower personnel-related expenses, facilities costs, transition services agreement (TSA) costs and SER-155 costs driven by lower activities in these areas and cost reduction efforts. General and administrative expenses were $7.1 million for the second quarter of 2026, compared with $10.3 million for the same period in 2025, due to lower personnel-related expenses, facilities costs, professional services fees, and IT costs, including those related to IT services provided under the TSA. In the second quarter of 2026, there was a $5.8 million impairment charge recorded related to the early termination of a portion of the Company’s leased space at 101 Cambridgepark Drive. There were no manufacturing services expenses in the second quarter of 2026, compared with $1.7 million in the second quarter of 2025, as the Company completed such services under the TSA at the end of 2025. Cash and Cash Runway As of June 30, 2026, Seres had $15.6 million in cash and cash equivalents. Based on Seres’ currently available cash resources, including the $12.5 million Milestone Termination Payment received from Nestlé on July 1, 2026, and the expected receipt of the remaining $12.5 million Milestone Termination Payment from Nestlé on October 1, 2026, and considering future operating plans, the Company expects to fund operations through the first quarter of 2027. This projection excludes proceeds from any potential future partnerships or other sources of capital. About Seres Therapeutics Seres Therapeutics, Inc. (Nasdaq: MCRB) is a clinical-stage biotechnology company developing novel live biotherapeutics products (LBP), designed to address unmet needs in oncology that can lead to interruption to patients' cancer care and/or mortality, and to treat inflammatory and immune (I&I) diseases, by modulating host function to protect and improve mucosal epithelial barrier integrity, induce immune homeostasis and tolerance, and prevent the colonization and overgrowth of pathogens in the gastrointestinal (GI) tract. The Company previously led the development and FDA approval of VOWST™, the first orally administered microbiome therapeutic, which was subsequently divested to Nestlé Health Science. SER-155, an investigational cultivated multi-strain biotherapeutic, which has received Breakthrough Therapy and Fast Track designations, is being advanced for the prevention of bloodstream infections in patients undergoing allogeneic hematopoietic stem cell transplant (allo-HCT), and is Phase 2 ready, pending receipt of funding. SER-155 is also being developed to address immune checkpoint inhibitor-related enterocolitis (irEC) to provide an immunosuppressive-free alternative and enable patients to continue their ICI cancer therapy. Having recently reported promising results from an IST, Seres is evaluating the design of a Phase 2 study in irEC. The Company is advancing IND-enabling studies for SER-603, which is in development for inflammatory bowel disease. Mechanistically, Seres' biotherapeutics target the mucosal epithelial barrier-immune interface and are optimized to modulate host function to increase mucosal epithelium integrity, induce immune homeostasis, and prevent the colonization and overgrowth of harmful bacteria in the GI tract. For more information, please visit Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including statements about: SER-155 and its intended uses and benefits in irEC; our clinical development plans for SER-155, SER-603 and SER-428; potential accessibility for patients; the timing and results of clinical studies and data readouts; current or future product candidates and their potential impacts and outcomes; engagement with potential partners and financing sources; our ability to access capital to advance our programs; expected receipt of milestone termination payments; our lease restructuring activities and anticipated cost savings and liability reductions; our cash runway; our planned strategic focus; the anticipated timing of any of the foregoing; and other statements that are not historical fact. These forward-looking statements are based on management's current expectations. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, but not limited to, the following: (1) our need for additional funding; (2) our ability to continue as a going concern; (3) we have incurred significant losses, are not currently profitable and may never become profitable; (4) our cost reduction actions may not achieve their intended benefits, including an extended cash runway; (5) our limited operating history; (6) we may not be able to realize the anticipated benefits of the VOWST sale, and may face new challenges as a smaller, less diversified company; (7) we have in the past and may in the future receive notice of the failure to satisfy a continued listing rule from The Nasdaq Stock Market LLC; (8) our novel approach to therapeutic intervention; (9) our reliance on third parties to conduct our clinical trials and manufacture our product candidates; (10) our ability to achieve market acceptance necessary for commercial success; (11) the competition we will face; (12) our ability to protect our intellectual property; (13) impact of our recent management transitions and appointments and our ability to retain key personnel; and (14) disruptions at the FDA or other government agencies. These and other important factors discussed under the caption "Risk Factors" in our Quarterly Report on Form 10-Q for the quarterly period ended June 30, 2026, to be filed with the Securities and Exchange Commission (SEC) on August 5, 2026, as well as our other reports filed with the SEC, could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. Any such forward-looking statements represent management's estimates as of the date of this press release. While we may elect to update such forward-looking statements at some point in the future, except as required by law, we disclaim any obligation to do so, even if subsequent events cause our views to change. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to the date of this press release. SERES THERAPEUTICS, INC. CONDENSED CONSOLIDATED BALANCE SHEETS (unaudited, in thousands, except share and per share data) June 30, December 31, 2026 2025 Assets Current assets: Cash and cash equivalents $ 15,594 $ 45,766 Accounts receivable due from SPN - related party 25,000 360 Accounts receivable 274 157 Prepaid expenses and other current assets 1,480 3,093 Total current assets 42,348 49,376 Property and equipment, net 5,798 7,635 Operating lease assets 51,168 72,483 Restricted cash 2,243 8,668 Other non-current assets 31 31 Total assets $ 101,588 $ 138,193 Liabilities and Stockholders’ Equity Current liabilities: Accounts payable $ 1,186 $ 1,682 Accrued expenses and other current liabilities 3,739 3,972 Accrued liabilities due to SPN - related party 3,278 3,278 Operating lease liabilities 11,828 10,390 Total current liabilities 20,031 19,322 Operating lease liabilities, net of current portion 44,816 72,576 Other long-term liabilities 2,207 2,077 Total liabilities 67,054 93,975 Commitments and contingencies (Note 9) Stockholders’ equity (deficit): Preferred stock, $0.001 par value; 10,000,000 shares authorized at June 30, 2026 and December 31, 2025; no shares issued and outstanding at June 30, 2026 and December 31, 2025 — — Common stock, $0.001 par value; 360,000,000 shares authorized at June 30, 2026 and December 31, 2025; 9,827,569 and 9,556,466 shares issued and outstanding at June 30, 2026 and December 31, 2025, respectively 10 10 Additional paid-in capital 1,022,259 1,016,611 Accumulated deficit (987,735 ) (972,403 ) Total stockholders’ equity 34,534 44,218 Total liabilities and stockholders’ equity $ 101,588 $ 138,193 SERES THERAPEUTICS, INC. CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS AND COMPREHENSIVE (LOSS) INCOME (unaudited, in thousands, except share and per share data) Three Months Ended June 30, Six Months Ended June 30, 2026 2025 2026 2025 Revenue: Grant revenue 736 — 1,094 — Total revenue 736 — 1,094 — Operating expenses: Research and development expenses 9,141 12,939 22,336 24,760 General and administrative expenses 7,061 10,253 15,131 22,141 Impairment of long-lived assets 5,807 — 5,807 — Manufacturing services — 1,689 — 5,216 Total operating expenses 22,009 24,881 43,274 52,117 Loss from operations (21,273 ) (24,881 ) (42,180 ) (52,117 ) Other income (expense): Gain on sale of VOWST Business 25,000 185 25,000 52,366 Interest income 181 546 506 1,164 Other income (expense) (1) 673 4,295 1,342 11,414 Total other income (expense), net 25,854 5,026 26,848 64,944 Net income (loss) and comprehensive income (loss) $ 4,581 $ (19,855 ) $ (15,332 ) $ 12,827 Net income (loss) per share attributable to common stockholders – basic $ 0.47 $ (2.27 ) $ (1.59 ) $ 1.47 Net income (loss) per share attributable to common stockholders – diluted $ 0.47 $ (2.27 ) $ (1.59 ) $ 1.47 Weighted average common shares outstanding - basic 9,706,193 8,743,733 9,644,704 8,723,589 Weighted average common shares outstanding - diluted 9,747,138 8,743,733 9,644,704 8,732,176 [1] Includes $0, $0, $3,490, and $9,799 for the three and six months ended June 30, 2026 and 2025 related to reimbursement received from SPN (related party) for transition services provided by the Company. Investor and Media Contact: IR@serestherapeutics.com Carlo Tanzi, Ph.D. Kendall Investor Relations ctanzi@kendallir.com

100 项与纳武利尤单抗/瑞拉利单抗相关的药物交易

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研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
转移性黑色素瘤	欧盟	Bristol-Myers Squibb Pharma EEIG	2022-09-15
转移性黑色素瘤	冰岛	Bristol-Myers Squibb Pharma EEIG	2022-09-15
转移性黑色素瘤	列支敦士登	Bristol-Myers Squibb Pharma EEIG	2022-09-15
转移性黑色素瘤	挪威	Bristol-Myers Squibb Pharma EEIG	2022-09-15
不可切除的黑色素瘤	欧盟	Bristol-Myers Squibb Pharma EEIG	2022-09-15
不可切除的黑色素瘤	冰岛	Bristol-Myers Squibb Pharma EEIG	2022-09-15
不可切除的黑色素瘤	列支敦士登	Bristol-Myers Squibb Pharma EEIG	2022-09-15
不可切除的黑色素瘤	挪威	Bristol-Myers Squibb Pharma EEIG	2022-09-15
黑色素瘤	美国	Bristol Myers Squibb Co.	2022-03-18

未上市

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适应症	最高研发状态	国家/地区	公司	日期
肿瘤	临床3期	美国	Bristol Myers Squibb Co.	2024-10-07
肿瘤	临床3期	日本	Bristol Myers Squibb Co.	2024-10-07
肿瘤	临床3期	阿根廷	Bristol Myers Squibb Co.	2024-10-07
肿瘤	临床3期	澳大利亚	Bristol Myers Squibb Co.	2024-10-07
肿瘤	临床3期	奥地利	Bristol Myers Squibb Co.	2024-10-07
肿瘤	临床3期	比利时	Bristol Myers Squibb Co.	2024-10-07
肿瘤	临床3期	巴西	Bristol Myers Squibb Co.	2024-10-07
肿瘤	临床3期	智利	Bristol Myers Squibb Co.	2024-10-07
肿瘤	临床3期	哥伦比亚	Bristol Myers Squibb Co.	2024-10-07
肿瘤	临床3期	丹麦	Bristol Myers Squibb Co.	2024-10-07

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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


NCT06101134 (CTgov)	临床2期	黑色素瘤 \| 转移性黑色素瘤	100	relatlimab+nivolumab+rHuPH20+relatlimab+nivolumab (Cohort 1: Metastatic Melanoma)	鑰糧餘壓鏇鏇製艱蓋網 = 膚獵鹹淵淵餘廠鹽憲鹽鏇網壓選製構積鏇製餘 (醖淵積顧繭鹽構淵構糧, 願壓醖鏇製築範壓積選 ~ 壓顧觸範蓋窪壓遞餘範) 更多	-	2026-04-09
				nivolumab+nivolumab+rHuPH20 (Cohort 2: Resected Melanoma)	鑰糧餘壓鏇鏇製艱蓋網 = 廠淵遞醖蓋膚窪網網糧鏇網壓選製構積鏇製餘 (醖淵積顧繭鹽構淵構糧, 繭願範膚淵壓積遞遞壓 ~ 願廠廠願醖觸遞範範願) 更多
NCT05002569 (RELATIVITY-098, CTgov)	临床3期	黑色素瘤 \| 转移性黑色素瘤	1,093	nivolumab+relatlimab (Treatment 1)	築窪鏇糧廠願獵壓鹹製(獵窪鹽餘鏇廠鑰糧艱醖) = 顧鹽憲選繭糧繭遞製鬱鹹膚觸簾願糧齋餘鬱餘 (鏇餘膚壓鑰艱餘選製積, 簾網醖憲廠夢餘夢醖膚 ~ 醖蓋築鏇願願鏇鬱獵窪) 更多	-	2026-01-08
				nivolumab (Treatment 2)	築窪鏇糧廠願獵壓鹹製(獵窪鹽餘鏇廠鑰糧艱醖) = 鹽憲積製齋蓋齋蓋顧艱鹹膚觸簾願糧齋餘鬱餘 (鏇餘膚壓鑰艱餘選製積, 壓構選鹹簾鑰觸醖淵夢 ~ 獵窪範積醖觸繭網網遞) 更多
NCT05002569 (RELATIVITY-098, Company_Website) 人工标引	临床3期	黑色素瘤辅助	-	Opdualag	鑰鏇憲淵鬱廠蓋網廠壓(醖築衊築齋餘範簾鬱選) = did not meet its primary endpoint. 淵淵蓋觸膚艱襯鏇繭鹽 (衊蓋壓積鏇餘憲糧製繭 ) 未达到	不佳	2025-02-13
				Opdivo
ESMO2024 人工标引	N/A	黑色素瘤二线 \| 一线 \| 新辅助	205	Nivolumab/Relatlimab	夢鏇憲製艱鹽蓋夢齋醖(遞淵網獵衊製鏇餘觸選) = 襯築窪醖壓繭鹹餘窪築窪觸蓋鏇觸構蓋繭夢築 (鏇獵簾鹽齋蓋遞製構構 ) 更多	积极	2024-09-14
				Nivolumab/Relatlimab (subsequent line(C2))	夢鏇憲製艱鹽蓋夢齋醖(遞淵網獵衊製鏇餘觸選) = 鹹顧蓋廠鬱鑰簾鏇鏇選窪觸蓋鏇觸構蓋繭夢築 (鏇獵簾鹽齋蓋遞製構構 ) 更多
NEWS 人工标引	临床2/3期	黑色素瘤	714	Opdualag	獵襯膚膚鏇鹽鑰餘齋積(築膚壓糧構範鏇顧鏇蓋) = 鹹襯醖網淵選膚鏇鏇鑰構齋糧夢選築齋製憲憲 (襯衊廠網築夢夢築選獵 )	积极	2024-01-03
				nivolumab	獵襯膚膚鏇鹽鑰餘齋積(築膚壓糧構範鏇顧鏇蓋) = 鏇齋範夢構範糧廠醖窪構齋糧夢選築齋製憲憲 (襯衊廠網築夢夢築選獵 )
NCT03662659 (RELATIVITY-060, CTgov)	临床2期	胃食管交界处癌 \| 胃食管交界处腺癌	274	BMS986213 (BMS986213 + Chemotherapy)	醖淵顧壓遞網遞顧鹹製 = 窪遞廠夢鏇獵衊淵願製簾構選艱鹹醖襯壓齋鹹 (鹽齋網鏇淵選鹹遞繭淵, 壓壓餘窪鹹鏇蓋衊鹹窪 ~ 壓築遞窪夢鏇鬱鑰膚壓) 更多	-	2022-05-09
				Nivolumab (Nivolumab + Chemotherapy)	醖淵顧壓遞網遞顧鹹製 = 蓋襯選壓齋醖壓襯鑰範簾構選艱鹹醖襯壓齋鹹 (鹽齋網鏇淵選鹹遞繭淵, 夢襯簾築鏇齋衊憲鹹齋 ~ 窪願簾獵窪鏇衊衊餘鬱) 更多