LIGHTBEAM-U01 Substudy 01B: A Phase 1/2 Substudy to Evaluate the Safety and Efficacy of Pembrolizumab in Combination With Investigational Agents in Pediatric and Young Adult Participants With Hematologic Malignancies or Solid Tumors

This study is a rolling arm study of pembrolizumab in combination with investigational agents in pediatric participants with relapsed or refractory classical Hodgkin lymphoma (cHL) solid tumors with microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR) or tumor mutational burden-high (TMB-H). This study will have 2 parts: a safety lead-in to demonstrate a tolerable safety profile and confirm a preliminary recommended phase 2 dose (RP2D) (Part 1) followed by an efficacy evaluation (Part 2). Participants will be assigned to a treatment arm (either Part 1 or Part 2) that is open for enrollment.
There will be no hypothesis testing in this study.

开始日期2025-01-15

申办/合作机构

Merck Sharp & Dohme LLC

NCT03598608

/ Active, not recruiting临床1/2期

A Phase 1/Phase 2 Clinical Study to Evaluate the Safety and Efficacy of a Combination of MK-4280 and Pembrolizumab (MK-3475) in Participants With Hematologic Malignancies

This study will evaluate the safety and efficacy of favezelimab (MK-4280) in combination with pembrolizumab (MK-3475) using a non-randomized study design in participants with the following hematological malignancies:
* classical Hodgkin lymphoma (cHL)
* diffuse large B-cell lymphoma (DLBCL)
* indolent non-Hodgkin lymphoma (iNHL)
This study will also evaluate the safety and efficacy of pembrolizumab or favezelimab administered as monotherapy in participants with cHL using a 1:1 randomized study design.
The study will have 2 phases: a safety lead-in and an efficacy expansion phase. The recommended Phase 2 dose (RP2D) will be determined in the safety lead-in phase by evaluating dose-limiting toxicities.
There is no primary hypothesis for this study.

开始日期2018-10-17

申办/合作机构

Merck Sharp & Dohme LLC

NCT03516981

/ Completed临床2期

A Phase 2 Precision Oncology Study of Biomarker-Directed, Pembrolizumab-(MK-3475, SCH 900475) Based Combination Therapy for Advanced Non-Small Cell Lung Cancer (KEYNOTE-495; KeyImPaCT)

This study will investigate the utility of biomarker-based triage for study participants with advanced non-small cell lung cancer (NSCLC) without prior systemic therapy. Study participants within groups defined by a biomarker-based classifier (gene expression profile [GEP] and tumor mutational burden [TMB]) will be randomized to receive pembrolizumab in combination with quavonlimab (MK-1308), favezelimab (MK-4280), or lenvatinib. The primary hypotheses are as follows: In participants receiving pembrolizumab in combination with either quavonlimab, favezelimab, or lenvatinib, the Objective Response Rate (ORR) will be 1) greater than 5% among participants with low GEP and low TMB, 2) greater than 20% among participants with low GEP and high TMB, 3) greater than 20% among participants with high GEP and low TMB, and 4) greater than 45% among participants with high GEP and high TMB.

开始日期2018-10-01

申办/合作机构

Merck Sharp & Dohme Corp.

100 项与 Favezelimab 相关的临床结果

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100 项与 Favezelimab 相关的转化医学

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100 项与 Favezelimab 相关的专利（医药）

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项与 Favezelimab 相关的文献（医药）

2025-10-14·Blood Advances

Estimating efficacy of favezelimab plus pembrolizumab relative to pembrolizumab in anti–PD-1–refractory Hodgkin lymphoma

Article

作者: Pillai, Pallavi ; Lavie, David ; Herrera, Alex F. ; Timmerman, John ; Thiagarajan, Kannan ; Armand, Philippe ; Topp, Brian G. ; Johnson, Nathalie A. ; Zinzani, Pier Luigi

Abstract:

Favezelimab plus pembrolizumab had promising efficacy in anti–programmed cell death protein 1 (PD-1)–refractory classical Hodgkin lymphoma in MK-4280-003; however, the contribution of favezelimab was unclear. Here, we assessed the relative contribution of favezelimab by comparison with data from participants treated with only pembrolizumab beyond progression in KEYNOTE-087. Participants in MK-4280-003 had received ≥2 doses of anti–PD-1 therapy and progressed <12 weeks of last dose. Participants eligible from KEYNOTE-087 had received >2 doses of pembrolizumab beyond progression, and progressed <12 weeks of last dose. Participants received pembrolizumab 200 mg plus favezelimab 200 mg or 800 mg, or pembrolizumab 200 mg IV every 3 weeks. Change in target lesion size and response per International Working Group 2007 criteria were assessed. Baseline tumor size was reset at first progression for KEYNOTE-087. A bootstrapping method compared change in target lesion size between groups. Twenty-seven participants from MK-4280-003 and 81 from KEYNOTE-087 were included. Objective response rates were 37% (95% confidence interval [CI], 15-51) for favezelimab plus pembrolizumab, and 2% (95% CI, 0-6) for pembrolizumab alone. A clinically meaningful reduction (≥50%) in target lesion size was observed in 13 (48%) vs 4 participants (5%), respectively. The mean change from baseline in target lesion size was −49% and −0.4%. In the bootstrapping analysis, 99.4% of samples showed greater decrease in tumor burden with favezelimab plus pembrolizumab. Favezelimab plus pembrolizumab had a higher response rate and greater reduction in tumor burden vs pembrolizumab alone in anti–PD-1–refractory classical Hodgkin lymphoma, suggesting favezelimab contributed substantially to efficacy in MK-4280-003. The trials were registered at www.clinicaltrials.gov as #NCT03598608 and #NCT02453594.

2025-10-01·ANNALS OF ONCOLOGY

Novel pembrolizumab-based treatments as first-line therapy in advanced clear cell renal cell carcinoma: Substudy 03A of the open-label, umbrella platform, phase I/II KEYMAKER-U03 trial

Article

作者: Shin, S J ; Hammers, H ; Kloster, A Zwenger ; Dziadziuszko, R ; Suttner, L ; Lee, J-L ; Miller, W H ; Peer, A ; Keizman, D ; Burgents, J E ; Powles, T ; Rojas, C ; Waddell, T ; Weickhardt, A ; Motzer, R ; Suarez, C ; Weber, P Yanez ; Neiman, V ; Albiges, L ; Sharma, M

BACKGROUND:

First-line triplet therapy may expand clinical benefit for advanced clear cell renal cell carcinoma (ccRCC). The phase Ib/II KEYMAKER-U03 Substudy 03A (NCT04626479) investigated novel pembrolizumab (pembro)-based regimens in this setting.

METHODS:

Participants with advanced ccRCC and no prior systemic therapy were randomized 2:1 to quavonlimab (qmab)/pembro plus lenvatinib (lenva), favezelimab (fave)/pembro plus lenva, pembro plus lenva plus belzutifan (bel), and vibostolimab (vibo)/pembro plus bel or a concurrent reference treatment (pembro plus lenva). A safety lead-in of ∼10 participants occurred for all investigative treatments before randomization. Primary endpoints were objective response rate (ORR) per RECIST v1.1 by blinded independent central review in all randomized participants (excluding safety lead-in), and safety in all treated participants. Secondary endpoints included progression-free survival (PFS) and overall survival (OS).

RESULTS:

As of March 31, 2025, 393 participants were enrolled. Median follow-up for randomized participants across the 5 cohorts ranged between 16 and 39 months. ORR (95% CI) was 80.6% (68.6-89.6) with pembro plus lenva, 71.3% (60.0-80.8) with qmab/pembro plus lenva, 62.7% (48.1-75.9) with fave/pembro plus lenva, 77.5% (66.8-86.1) with pembro plus lenva plus bel, and 42.5% (31.5-54.1) with vibo/pembro plus bel. Median PFS (95% CI) in months was 26.3 (15.3-39.8) with pembro plus lenva, 18.0 (11.6-34.3) with qmab/pembro plus lenva, 26.0 (8.2-31.8) with fave/pembro plus lenva, 31.8 (26.3-NR) with pembro plus lenva plus bel, and 15.2 (12.4-NR) with vibo/pembro plus bel. Median OS was not reached in any arm. Grade ≥3 treatment-related adverse events occurred in 71.0% (44/62) of participants treated with pembro plus lenva, 73.3% (66/90) with qmab/pembro plus lenva, 86.9% (53/61) with fave/pembro plus lenva, 70.0% (63/90) with pembro plus lenva plus bel, and 68.9% (62/90) with vibo/pembro plus bel.

CONCLUSIONS:

Observed efficacy and safety of pembro plus lenva were confirmatory of prior observations for this combination. ORR was similar to reference for pembro plus lenva plus bel and qmab/pembro plus lenva, but not the other investigative arms. Further investigation of pembro plus lenva plus bel and qmab/pembro plus lenva versus pembro plus lenva is ongoing in the phase 3 LITESPARK-012 study.

2023-10-01·STRUCTURE

CryoEM structure of a therapeutic antibody (favezelimab) bound to human LAG3 determined using a bivalent Fab as fiducial marker

Article

作者: Agnihotri, Pragati ; Hasan, S Saif ; Kolesnikov, Alexander ; Karade, Sharanbasappa S ; Mariuzza, Roy A ; Mishra, Arjun K ; Shahid, Salman

Lymphocyte activation gene 3 protein (LAG3) is an inhibitory receptor that is upregulated on exhausted T cells in tumors. LAG3 is a major target for cancer immunotherapy with many anti-LAG3 antibodies in clinical trials. However, there is no structural information on the epitopes recognized by these antibodies. We determined the single-particle cryoEM structure of a therapeutic antibody (favezelimab) bound to LAG3 to 3.5 Å resolution, revealing that favezelimab targets the LAG3-binding site for MHC class II, its canonical ligand. The small size of the complex between the conventional (monovalent) Fab of favezelimab and LAG3 (∼100 kDa) presented a challenge for cryoEM. Accordingly, we engineered a bivalent version of Fab favezelimab that doubled the size of the Fab-LAG3 complex and conferred a highly identifiable shape to the complex that facilitated particle selection and orientation for image processing. This study establishes bivalent Fabs as new fiducial markers for cryoEM analysis of small proteins.

项与 Favezelimab 相关的新闻（医药）

2025-10-30

·PRNewswire

Clinical Late-Breaking Abstracts Announced for the Society for Immunotherapy of Cancer's 40th Anniversary Annual Meeting

MILWAUKEE, Oct. 30, 2025 /PRNewswire/ -- The Society for Immunotherapy of Cancer (SITC) received an incredible number of abstract submissions in 2025, more than 1,300, including many clinical based Late-breaking Abstracts. SITC is proud to announce the titles and authors for the clinical Late-breaking Abstracts (LBA) . The abstracts will be presented at SITC's upcoming 40th Anniversary Annual Meeting & Pre-Conference Programs taking place Nov. 5–9, 2025, in National Harbor, MD and virtually. Continue Reading SITC 2025 Logo "We are excited to incorporate these clinical abstracts into an already impressive lineup of abstracts that will be presented at SITC. The Late-breaking Abstracts this year will only focus on late-breaking data from interventional clinical trials in humans and will further enhance the cutting-edge science offered at the 40th Anniversary Annual Meeting," said SITC Vice President Sandra Demaria MD. "SITC is committed to accelerating the approval of 100 novel agents by 2034, and providing a platform to showcase the latest clinical advancements at our Annual Meeting is an important component of this goal." The Late-breaking Abstracts with oral presentations at the 40th Anniversary Annual Meeting are: (1316) Initial monotherapy clinical activity of invikafusp alfa, a first-in-class TCR β-chain-targeted bifunctional antibody, in tissue-agnostic, TMB-H patients from STARt-001, a Phase 1/2 trial Aurélien Marabelle, MD, PhD – Gustave Roussy & Paris Saclay University Session 104: Clinical Oral Abstract Session – Friday, Nov. 7, 2025 – 11:30 a.m. ET (1342) First-in-human dose escalation study to investigate the safety, pharmacokinetics, pharmacodynamics and initial efficacy of mRNA-LNP MT-302 in vivo CAR therapy in solid tumors Rasha Cosman, BSc (Med), MBBS, FRACP – St. Vincent's Hospital Session 104: Clinical Oral Abstract Session – Friday, Nov. 7, 2025 – 11:30 a.m. ET (1348) Final overall survival analysis of HARMONi-A study comparing ivonescimab plus chemotherapy to chemotherapy alone in patients with EGFR+ NSCLC progressed on EGFR-TKI treatment Li Zhang, MD – Sun Yat-Sen University Cancer Center Session 104: Clinical Oral Abstract Session – Friday, Nov. 7, 2025 – 11:30 a.m. ET (1305) Coformulation of favezelimab and pembrolizumab as neoadjuvant therapy for resectable cutaneous squamous cell carcinoma (cSCC): results from cohort A of the phase 2 KeyForm-010 study Matteo Carlino, MBBS, PhD, BMedSC, FRACP – The University of Sydney Session 106a: Considerations for Incorporating Biomarkers in Perioperative/Neoadjuvant Therapy – Friday, Nov. 7, 2025 – 1:45 p.m. ET (1346) Molecular and immunologic correlates of response in a phase II study of neoadjuvant lenvatinib plus pembrolizumab in Merkel cell carcinoma Kenneth Tsai, MD, PhD – Moffitt Cancer Center Session 106a: Considerations for Incorporating Biomarkers in Perioperative/Neoadjuvant Therapy – Friday, Nov. 7, 2025 – 1:45 p.m. ET (1327) Biomarker and updated clinical data for RP1 plus nivolumab in anti-PD-1-failed melanoma from the IGNYTE trial demonstrate reversal of mechanisms of resistance to immune checkpoint blockade Trisha Wise-Draper, MD, PhD– University of Cincinnati Cancer Center Session 107d: The Next Wave: Viruses, Cells and Next-gen PD-1 Bispecifics – Friday, Nov. 7, 2025 – 3:55 p.m. ET (1328) SSGJ-707, a PD-1/VEGF bispecific antibody, combined with platinum-based chemotherapy in first-line treatment of advanced non-small cell lung cancer (NSCLC): results from a phase 2 study Lin Wu, PhD –Hunan Cancer Hospital Session 107d: The Next Wave: Viruses, Cells and Next-gen PD-1 Bispecifics – Friday, Nov. 7, 2025 – 3:55 p.m. ET (1310) A phase 1/IIa study of ILKN421H, a LNP mRNA encoding an IL2Rβγ selective IL-2v, as monotherapy and in combination with pembrolizumab, in patients with advanced solid tumors Haining Huang, PhD- ILeukon Therapeutics Session 206: Clinical Oral Abstract Session – Saturday, Nov. 8, 2025 – 1:45 p.m. ET (1325) SCOPE, an open label phase 2 parallel multi cohort clinical trial evaluating an off-the-shelf DNA plasmid vaccine in first line advanced melanoma combined with check point blockade - interim read-out Nermeen Varawalla, MD, PhD, MBA – Scancell Ltd Session 206: Clinical Oral Abstract Session – Saturday, Nov. 8, 2025 – 1:45 p.m. ET (1336) Final ph1b/2 results for Nous-209 monotherapy in Lynch syndrome carriers: Annual revaccination boosts T cell immunity informing future cancer interception strategies Anna Morena D'Alise, PhD – Nouscom SRL Session 206: Clinical Oral Abstract Session – Saturday, Nov. 8, 2025 – 1:45 p.m. ET (1340) Lead-in therapy targeting PD1 and/or LAG3 distinguishes differential impacts upon the immune response in first-line treatment of metastatic melanoma Lilit Karapetyan, MD – Moffitt Cancer Center Session 206: Clinical Oral Abstract Session – Saturday, Nov. 8, 2025 – 1:45 p.m. ET (1345) Initial phase 1a/1b results of STK-012, an α/β IL-2 receptor biased partial agonist, with pembrolizumab, pemetrexed, and carboplatin in 1L PD-L1 negative non-squamous NSCLC Adam Schoenfeld, MD – Memorial Sloan-Kettering Cancer Center Session 206: Clinical Oral Abstract Session – Saturday, Nov. 8, 2025 – 1:45 p.m. ET The full Regular and Young Investigator Award abstracts will be available on Nov. 4 at 9 a.m. ET and LBA – Clinical Only abstracts will be made available on Nov. 7 at 9 a.m. ET. Both types of abstracts will be published in the Journal for ImmunoTherapy of Cancer (JITC) Clinical Late-breaking Abstract Sessions with oral abstract presentations will take place on Friday, Nov. 7 from 11:30 a.m.–12:15 p.m. CT and Saturday, Nov. 8 from 1:45–3 p.m. ET in the Gaylord National Resort and Convention Center - Ballroom Level - Potomac Ballroom. In addition, Late-breaking Abstract posters will be presented in the Exhibit and Poster Hall and the virtual ePoster Hall beginning Friday, Nov. 7 at 10 a.m. ET. To learn more about the Late-breaking Abstracts, visit the 40th Annual Meeting & Pre-Conference Programs website. To register for the 40th Anniversary Annual Meeting and Pre-Conference Programs, click here. About SITC The Society for Immunotherapy of Cancer (SITC) is the world's leading member-driven organization specifically dedicated to improving cancer patient outcomes by advancing the science and application of cancer immunotherapy. Established in 1984, SITC, a 501(c)(3) not-for-profit organization, serves scientists, clinicians, academicians, patients, patient advocates, government representatives and industry leaders from around the world. Through educational programs that foster scientific exchange and collaboration, SITC aims to one day make the word cure a reality for cancer patients everywhere. To learn more, visit and follow us on X, LinkedIn, Facebook and YouTube. SOURCE Society for Immunotherapy of Cancer (SITC) WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

临床2期临床结果免疫疗法疫苗

2025-07-25

·贝壳社

开盘涨超110%，维立志博今日港股上市

作者：贝壳社今日，维立志博（09887.HK）正式港股上市。开盘涨幅达118.85%，市值超110亿港元。日前，维立志博公布了其全球发售H股的配发结果。全球发售3686.25万股H股，其中香港公开发售占43.48%，国际发售占56.52%。最终发售价定为每股35港元。此次IPO，维立志博认购场面火爆，据富途数据显示，其融资申购倍数已超过3000倍，融资申购金额高达3300亿港元。01达成超13亿美元BD招股书显示，维立志博成立于2012年，是一家临床阶段生物科技公司，专注于肿瘤、自身免疫性疾病及其他重大疾病新疗法的发现、开发及商业化。截至目前，维立志博拥有超10款创新候选药物的差异化临床管线，其中6款已成功进入临床阶段，4款主要产品均处于全球临床进度领先的候选药物之列。从成立至今，维立志博共完成了8轮股权融资，累计募集资金约1.51亿美元。其估值也从Pre-A轮的9,700万元增长到C+轮的31.3亿元，实现了指数级增长。此次IPO招股引入基石投资者9席，共认购6900万美元(约5.42亿港元)，包括正心谷资本、高毅、OrbiMed、TruMed、腾讯、易方达、睿远、SAGE和汉康资本。维立志博目前处于产品上市前的研发阶段，因此几乎没有营业收入。招股书显示，其在2022年和2024年上半年均无收入。2023年确认的890万元收入，并非来自产品销售，而是根据与百济神州的协议，为其提供的桥接研究服务收到的款项。对于一家未盈利的生物科技公司，获得行业领先企业的认可与合作，是其技术和管线价值最直接、最有力的证明。维立志博对外合作策略不仅带来了可观的现金流，更实现了资本效率的最大化。2021年12月，维立志博与百济神州达成协议，授予后者在大中华区以外开发、生产和商业化其LAG-3抗体LBL-007的独家权利。该交易的总金额高达7.72亿美元，包括首付款、里程碑付款以及未来销售额的分级特许权使用费。2024年11月，维立志博与Aditum Bio通过NewCo合作，致力于在全球范围内开发和商业化维立志博的CD3/CD19/BCMA三特异性T细胞衔接器LBL-051。该交易总价值高达6.14亿美元，此外维立志博还将获得潜在的特许权使用费以及在新公司中的股权。LBL-051通过同时靶向CD19和BCMA，有望在多种抗体介导的自身免疫性疾病中清除更广泛的病理性B细胞，从而激发更强效且持久的疗效。02专注创新药神经内分泌癌（NEC）是一种高度增殖性肿瘤，约占神经内分泌肿瘤的10%～20%，肺、消化道、膀胱等多种器官均可发病。其中肺外神经内分泌癌(EP-NEC)与小细胞肺癌高侵袭转移特征相似，疾病进展迅速。目前，晚期EP-NEC的一线治疗主要以含铂化疗为主，ORR约为30%～50%，中位生存时间（mOS）仅1年左右。据弗若斯特沙利文数据显示，2024年全球EP-NEC患者约5.8万，中国1.5万。4-1BB靶点因其强大的免疫激活潜力和难以克服的毒性问题，包括BMS、辉瑞在内的多家巨头都曾尝试开发4-1BB激动剂，但均因严重的肝毒性而宣告失败或中止。LBL-024是一种PD-L1与4-1BB双靶向双特异性抗体，有望成为首款获批的EP-NEC靶向疗法，目前处于关键临床阶段。LBL-024可解除PD-1/L1免疫抑制并强化4-1BB调节的T细胞激活，实现协同消灭肿瘤的效果，具有较PD-1/L1抑制剂更强的广谱癌症治疗潜力。在中国的I/II期临床试验中，LBL-024不论作为单药疗法或与化疗联合使用，均对治疗晚期EP-NEC表现出令人鼓舞的疗效信号且安全性良好。LBL-024于2024年4月30日获药品审评中心（CDE）批准开展单臂关键注册临床研究。2024年10月，LBL-024获CDE突破性治疗药物认定（BTD），2024年11月获FDA孤儿药认定（ODD）。除神经内分泌癌之外，维立志博计划逐步拓展LBL-024在非小细胞肺癌、胆道肿瘤、卵巢癌等多种常见癌症类型中的治疗应用，有望将其打造为一款前景广阔的、适用于多种适应症的有效抗肿瘤药物。除了LBL-024，维立志博还拥有一个由其他临床阶段候选药物组成的、具有深度和广度的产品组合。LBL-007：一款靶向LAG-3免疫检查点的单克隆抗体，LAG-3是继PD-1和CTLA-4之后最重要的下一代免疫检查点之一。维立志博已将该资产在大中华区外的权益授权给百济神州。此外，维立志博探索其在鼻咽癌等相对“蓝海”适应症中的应用，也体现了其差异化开发策略。BMS的Opdualag作为首个获批的LAG-3疗法，已经迅速成为重磅炸弹级产品。其2024年的销售额为8.7亿美元，BMS预计其峰值销售额有望达到40亿美元。此外，默克（Favezelimab）、再生元（Fianlimab）、诺华（LAG525）等，其中多款药物已进入后期临床开发阶段，竞争相对激烈。LBL-034：一款靶向GPRC5D和CD3的T细胞衔接器，主要用于治疗多发性骨髓瘤。GPRC5D是一个在骨髓瘤细胞上高表达的新兴靶点。LBL-034采用的2:1不对称设计旨在提升安全性，降低细胞因子风暴的风险。LBL-033：一款靶向MUC16和CD3的T细胞衔接器，MUC16（也称CA-125）是在卵巢癌等多种上皮性肿瘤中高表达的靶点。开发针对此类靶点的TCE疗法，有望将免疫治疗的范围扩大到更多“冷”肿瘤。此外，管线中还包括LBL-019（靶向TNFR2的抗体）、LBL-015（PD-1/TGFβR2双特异性抗体）等。这些项目共同展示了维立志博在肿瘤免疫领域的深度布局，其策略是系统性地开发能够克服第一代IO疗法耐药性的新机制药物。03 技术平台：创新的引擎维立志博的持续创新能力，建立在其LeadsBody™平台、X-body™平台在内的专有技术平台之上。这些平台不仅是其当前管线的基石，也是未来持续产出创新候选药物的保障。LeadsBody™平台专注于开发TCE疗法，维立志博在该平台的设计上同样追求差异化。以其GPRC5D/CD3双抗LBL-034为例，采用了非对称的2:1结构（两个GPRC5D结合域，一个CD3结合域）。这种设计旨在降低非抗原依赖性的T细胞激活，从而减少细胞因子释放综合征（CRS）等严重副作用的风险，在保证强效杀伤的同时寻求更优的安全性窗口。高价值对外授权的三特异性抗体LBL-051的成功，进一步验证了该平台的技术实力和商业潜力。X-Body™平台专注于设计靶向4-1BB的双特异性抗体，其核心产品LBL-024正是基于此平台开发。4-1BB是T细胞上一种强效的共刺激分子，能显著增强T细胞的抗肿瘤活性，但其系统性激动会导致严重的肝毒性。X-Body™平台通过设计一种特殊的2:2对称四价抗体结构，实现了“条件性激动”。康方生物、维立志博的核心战略均聚焦于开发具有FIC、BIC潜力的创新抗体药物，特别是技术壁垒较高的双特异性抗体。其中，维立志博成立之初便战略性地避开了当时竞争激烈的PD-1赛道，转而攻克更具挑战性的下一代免疫治疗靶点。其核心技术平台包括专为解决4-1BB激动剂毒性问题设计的X-Body™平台，以及开发TCE疗法的LeadsBody™平台，旨在实现差异化竞争和技术革新。康方生物核心的Tetrabody™技术平台专注于高效开发创新的四价双特异性抗体，并成功开发出全球首款获批上市的卡度尼利单抗（PD-1/CTLA-4双抗），以及依沃西单抗（PD-1/VEGF双抗），充分证明了其在双抗领域的全球领先地位。然而，康方生物多款产品获批上市，创造了显著的销售收入。而维立志博目前仍处于临床阶段，尚无产品获批上市，其估值高度依赖于核心产品LBL-024（PD-L1/4-1BB双抗）的临床和获批上市。但康方生物的成功，为维立志博展示了一条从临床研发走向商业成功的可行路径。对于维立志博而言，此次IPO只是一个新的起点。未来，LBL-024的成功将是驱动价值的核心引擎，而多元化的管线和BD合作策略则为其提供了潜在的增长空间。后续发展如何，仍需拭目以待。往期推荐1医健企业前沿动态2医健行业BD/出海/投融资洞察___*声明：本文仅为作者观点，不构成任何投资建议，且非治疗方案推荐素材来源官方媒体关于贝壳社贝壳社是国内领先的医健创新创业服务平台，构建了"产业空间+创业教育+投资孵化+资本运作"四位一体服务体系，为医健领域创业企业提供全周期赋能。通过深度挖掘高成长项目、精准匹配产业资源及全球化生态网络，覆盖企业从孵化培育到加速发展的全链路，重点提供包括空间落地、创业培训、资本运作及跨境资源链接服务。贝壳社以加速科学技术成果转化与产业升级为目标，致力于成为医健领域的孵化器、加速器、连接器。

IPO引进/卖出财报

2025-04-09

·VIP说

肿瘤免疫治疗策略2.0

# 本篇笔记仅基于公开资料和信息撰写、为个人观点、供学术交流所用、不构成任何建议 #我用了差不多一个月的时间，看了几十家代表公司的产品线、几千篇研报和点评、几万个注册临床试验，想要看清楚肿瘤免疫治疗棋局的现状和未来。这不符合我的本性，我是宁可去无人区探险，也不想投入毫厘铢锱不能差错的极致内卷中。但是，现实就是，现在和未来很长一段时间内，免疫检查点抑制剂都会是肿瘤治疗的基石，即使MNC们早就已经布局于免疫检查点抑制剂之外甚至肿瘤治疗之外，国内大多数药企还有一段国产替代的长路要走。既然不能提前退休，只能强忍着非常严重的内卷PTSD看棋局，这种不适感压制了我的段子手级别语言天赋，所以这篇笔记会写的非常......直白。我个人给免疫治疗策略1.0的定义，就是大家手里都有个PD-(L)1抑制剂产品。全球已经有32个/国内已经有24个PD-(L)1抑制剂产品上市。图片引用来自“IO笔记”。至于免疫治疗策略2.0，就是如何进一步迭代和升级。PD-(L)1抑制剂产品本身的迭代和升级，目前大家的策略非常一致，改良单抗本身没能创造出什么奇迹，就开发双抗/多抗和复方，以及皮下注射、口服小分子、ADC等新剂型。双抗/多抗和复方本质类似于联合给药方案，所以放到后面再说。开发皮下注射剂型看上去是个捷径，不过如果大家的目标是国际市场，可能会有专利侵权风险：阿斯利康7.5亿美元引进Alteogen透明质酸酶技术，后者深陷侵权风险口服小分子PD-(L)1抑制剂，我是没有“小药说药”那么关注，而且似乎已经冷却：靶向PD-1/PD-L1小分子药物的研究进展至于PD-(L)1 ADC，反正已经热闹起来：靶向PD-L1 ADC：辉瑞首次国内申报临床！复宏汉霖、映恩生物“勇攀高峰”此外，国内外很多家药企已经想开了，不搞什么伪创新药，帕博利珠单抗核心专利将于2028年到期，直接开发生物类似药。国内外我已经数出来10个帕博利珠单抗类似药在做注册临床试验了，还有3个纳武利尤单抗生物类似药。更广谱的迭代和升级策略，就是以PD-(L)1抑制剂产品为基石，开发各种联合给药方案。汇总信息还是医药魔方做得最漂亮（反正我下载了PPT）：PD-1/PD-L1抑制剂中美获批及全球注册性临床试验15年动态趋势医药魔方PPT中部分内容截图：类似的汇总信息报告和点评很多，都能让大家一眼看清楚肿瘤免疫治疗棋局已经内卷到什么地步，看完不但没有思路，反而更加焦虑了。所以我们还是采用最简单高效的fast follow的老办法，看看几十家代表公司的肿瘤免疫治疗产品线，看看follow谁家的具体策略最适合自家。1. 默沙东/默克帕博利珠单抗(PD-1单抗)，长期被群殴和围攻的药王，王冠太重。在肿瘤领域，默沙东/默克不断探索和拓展其各种联合给药方案，并且积极布局复方和皮下等新剂型，双抗等新产品，以求夯实其在肿瘤领域的领先地位。复方主要是MK-1308A(PD-1+CTLA-4，Pembrolizumab+Quavonlimab)，MK-7684A(PD-1+TIGHT，Pembrolizumab+Vibostolimab)，MK-4280A(PD-1+LAG-3，Pembrolizumab+favezelimab)，2024年12月宣布终止开发后两个，目前只有MK-1308A还在推进。皮下剂型MK-3475A的III期临床试验刚官宣成功。近年来，默沙东/默克的肿瘤产品线重点已经布局于免疫检查点抑制剂之外，但免疫检查点抑制剂还是肿瘤治疗的基石，肿瘤领域且没有禁忌症，什么新产品都尝试联联看，就像吃什么菜都要配一碗白米饭。看帕博利珠单抗适应症布局是一项极其艰巨的工作，我差不多用了半个月时间，剩下几十个产品用了剩下的半个月时间。太多了。不仅因为默沙东/默克财大气粗，有把握的III期试验开几百个，没把握的I-II期试验和IIT开几千个，更因为帕博利珠单抗是基石中的基石，米饭中的白米饭，其他药企开发联合给药方案也是首选帕博利珠单抗。即使默沙东/默克没有布局，其他药企也会填空，所有瘤种所有适应症，完全没有空缺。最后得去翻默沙东/默克官网的PPT，才能找出他家真正的主线。如果布局图里出现了个别空缺，那也是某些III期临床试验失败导致的，绝不是没人尝试过填空。比如大家都吃过瓜的LEAP系列。但是有三个瘤种，即著名的冷肿瘤们，卵巢癌、胰腺癌、前列腺癌，所有药企都是屡战屡败+屡败屡战。先驱栽坑里那是代价，后来者再盲目跳坑，我可能忍不住嘲笑了，如果不是颠覆性作用机制的新药，建议不要再尝试将免疫治疗用于这几个瘤种。2. BMS纳武利尤单抗(PD-1单抗)，没能问鼎药王，所以在此基础上早早开发出皮下注射剂型，与伊匹木单抗(Ipilimumab, CTLA-4)联合方案，与Relatlimab(LAG-3单抗)联合方案，甚至开发了复方OPDUALAG(Nivolumab+Relatlimab)，均已成功获批多个适应症。也曾在TIGHT、IDO等靶点药物联合方案上栽过跟头，最新产品是复方BMS-986489(PD-1+fucosyl-GM1, Nivolumab+BMS-986012)。近年来，BMS的肿瘤产品线重点也已经布局于免疫检查点抑制剂之外。但免疫检查点抑制剂还是肿瘤治疗的基石，主动或被动开发联合方案也非常多。3. 罗氏阿替利珠单抗(PD-L1单抗)，其实已经算差异化开发了，靶点从PD-1换成了PD-L1。阿替利珠单抗是早早成功开发了皮下注射剂型。之后开发双抗时换回PD-1单抗，包括Tobemstomig(RO7247669, PD-1/LAG-3)，Lomvastomig(PD-1/TIM-3, RO7121661)。罗氏在肿瘤免疫治疗方面不算成功，主要是因为阿替利珠单抗与Tiragolumab(TIGHT单抗)的联合方案投入太大，受伤太深。但是深挖一下新技术平台，还能翻出来PD1-IL2v，PDL1 LNA等产品。值得注意的是，阿替利珠单抗用于三阴性乳腺癌非常波折，各种姿势的III期临床试验失败和撤回适应症，鉴于特瑞普利单抗在同一适应症里取得过成功，咱们不能说三阴性乳腺癌不适合免疫治疗，但PD-1单抗似乎比PD-L1单抗强一些。肾癌、尿路上皮癌、头颈癌、宫颈癌里也有类似情况，建议谨慎选择PD-L1单抗。4. 阿斯利康度伐利尤单抗(PD-L1单抗)，早期策略和BMS类似，开发皮下注射剂型，还有和替西木单抗(Tremelimumab, CTLA-4)的联合给药方案。后来者的好处就是可以避开先驱们栽过的坑，适应症开发都比较顺利。现在已经不做复方了，直接换双抗，Volrustomig(PD-1/CTLA-4)，Sabestomig(PD-1/TIM-3)，Rilvegostomig (PD-1/TIGHT)。发起IO+ADC潮流的应该就是他家，而且他家明显艺高人胆大，最偏爱Rilvegostomig (PD-1/TIGHT)，这是要死磕TIGHT靶点的节奏。5. 辉瑞、吉列德、再生元、GSK、Incyte、BIOCAD可以说，辉瑞几乎错了肿瘤免疫治疗浪潮。Avelumab(PD-L1单抗)开发顺位非常靠后，所以从超级冷门小适应症下手—皮肤默克尔细胞癌，弯道超车获批上市后，目前仅在膀胱癌领域取得成功（联合阿昔替尼用于肾癌一线是基于PFS成功附条件获批，但是OS失败，现在很尴尬；用于非小细胞肺癌、头颈癌和胃癌都是全面失败）。后来一度想悄悄开发PD-1单抗皮下注射剂型Sasanlimab（未获批上市），最终还是抢跑PF-08046054(PD-1 ADC)。后来者后来到辉瑞这个地步，如果还不愿赌服输，就得这么另辟蹊径。但是Sasanlimab有点过，首个适应症居然选择联合BCG用于非肌层浸润性膀胱癌，之前帕博利珠单抗和纳武利尤单抗都挑战失败的适应症，全球均未有免疫检查点抑制剂类产品获批。吉列德也是后来者，但是通过收购Arcus获得了赛帕利单抗(Zimberelimab，PD-1单抗)，果然顺产没有顺手快。在国内，赛帕利单抗用于经典型霍奇金淋巴瘤和晚期宫颈癌已获批上市。但是他家的联合给药方案，目前以Domvanalimab(TIGHT单抗)为主，又是一个死磕TIGHT靶点的。再生元不算后来者，Cemiplimab(PD-1单抗)虽然不算先驱，但是通过小适应症—皮肤鳞状细胞癌和皮肤基底细胞癌，早早弯道超车获批上市。他家毕竟是资深肿瘤免疫疗法biotech，联合给药方案非常多，目前以联合Fianlimab(LAG-3单抗)为主。GSK不算后来者也不算先驱，多塔利单抗(Dostarlimab，PD-1单抗) 通过小适应症—dMMR/MSI-H子宫内膜癌，早早弯道超车获批上市，之后仅专注于子宫内膜癌、结直肠癌和头颈癌，坚定的反内卷思维，深得我心。Incyte真不容易，当初为了卡瑞利珠单抗和恒瑞分分合合，最后终于拥有了自己的Retifanlimab(PD-1单抗)。跟辉瑞类似，因为Retifanlimab开发顺位非常靠后，所以从超级冷门小适应症下手—皮肤默克尔细胞癌，弯道超车获批上市。后来居然又被再鼎引入中国继续开发，反正各种不容易。再看Incyte产品线，始终专注于肿瘤免疫疗法，口服PD-L1，PD-1/LAG-3双抗、PD-1/TGF-βRII双抗均有布局。Prolgolimab(PD-1单抗)由俄罗斯药企BIOCAD开发，获得俄罗斯卫生部批准上市，用于治疗转移性黑色素瘤。在两国总理的共同见证下，由上药集团引进入国内共同开发，上药集团不愧是一流国企，非常正确。值得一提的是，Prolgolimab都这么正确了也没有躺平，继续开发复方BCD-217(Prolgolimab+Nurulimab，PD-1+CTLA-4)，还开发了帕博利珠单抗生物类似药。6. 其他外企艾博维：Budigalimab(PD-1单抗)Budigalimab绝对算后来者，我个人高度怀疑艾博维是为了联合其他自家真爱的新产品才被迫开发了基石。到现在最高开发阶段II期临床试验。强生：Cetrelimab(PD-1单抗)也不知道这个产品是不是和辉瑞的Sasanlimab高度类似，首个适应症居然也选择非肌层浸润性膀胱癌，但联合了自家TAR-200，我个人觉得就是为了陪衬TAR-200。2025年1月15日，强生宣布递交TAR-200的上市申请，用于治疗卡介苗（BCG）不应答的高危非肌肉侵袭性膀胱癌（HR-NMIBC）伴原位癌（CIS）患者。此次递交通过实时肿瘤审评（RTOR）项目，允许FDA在完全申请正式递交之前就开始审评以加快进度。 TAR-200为一种膀胱内局部给药的新型递送系统，采用一种双重小片设计，材质为硅聚合物半透小管，吉西他滨在膀胱持续缓慢释放。BI：Ezabenlimab(PD-1单抗)反正我个人高度怀疑BI是为了联合其他自家真爱的新产品才被迫开发了基石。到现在最高开发阶段II期临床试验。安进：Zeluvalimab(PD-1单抗)在安进最新的产品线信息里已经找不到Zeluvalimab了，但是找到了纳武利尤单抗生物类似药，预期2025年获批上市。放弃死磕开发顺位过于滞后的伪创新药，拥抱生物类似药，拥抱效率和利润，毕竟肿瘤免疫治疗也不是安进公司的主线，顶多用来联合其他自家真爱的新产品。Agenus：Botensilimab(PD-1单抗)Agenus还算比较重视Botensilimab，但主要是为了配合新一代产品—Balstilimab(CTLA-4单抗)，声称可以将冷肿瘤转化为热肿瘤。首个适应症选择联合Balstilimab用于non-MSI-H结直肠癌。坚定的反内卷思维，深得我心。BioNTech：BNT327(PD-L1/VEGF双抗)等收购普米斯生物等biotechs，跳过肿瘤免疫治疗1.0时代，直接飞跃至2.0时代潮头，拥有各种最热门双抗和ADC，又是顺产哪有顺手快的成功案例和典型代表。不过最新的消息是BNT311(PD-L1/4-1BB双抗)退回Genmab，这不是一个好消息，真正成功的双抗也不多。BioNTech的策略虽然有抄袭AZ，但非常清晰明确，值得学习。先分析免疫检查点抑制剂单药或既往的联合给药方案，在全球范围内获批过哪些适应症，还有哪些细分人群中有未被满足的临床需求，既往放弃开发或开发失败适应症的困难在哪里。再分析或补充自家产品线里的产品，是否有新颖的作用机制可能攻克之前的困难。最后设计BNT327的临床开发计划：第一步，联合化疗去攻克确定性高、能快速实现高市场价值的适应症；第二步，联合各种新颖作用机制的新产品，填补之前未被满足的临床需求；第三步，探索更多、更新的联合给药方案和适应症。篇幅原因，写完外企部分已经快5000字了，改天再写国内企业部分。信息量过大，CPU干烧到头晕，所有重点点到即止，如有疏漏错误，请大家多包涵。# 本篇笔记仅基于公开资料和信息撰写、为个人观点、供学术交流所用、不构成任何建议 #

抗体药物偶联物免疫疗法生物类似药

100 项与 Favezelimab 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
实体瘤	临床3期	美国	Merck Sharp & Dohme Corp.	2018-08-21
实体瘤	临床3期	中国	Merck Sharp & Dohme Corp.	2018-08-21
实体瘤	临床3期	日本	Merck Sharp & Dohme Corp.	2018-08-21
实体瘤	临床3期	阿根廷	Merck Sharp & Dohme Corp.	2018-08-21
实体瘤	临床3期	澳大利亚	Merck Sharp & Dohme Corp.	2018-08-21
实体瘤	临床3期	奥地利	Merck Sharp & Dohme Corp.	2018-08-21
实体瘤	临床3期	比利时	Merck Sharp & Dohme Corp.	2018-08-21
实体瘤	临床3期	巴西	Merck Sharp & Dohme Corp.	2018-08-21
实体瘤	临床3期	加拿大	Merck Sharp & Dohme Corp.	2018-08-21
实体瘤	临床3期	智利	Merck Sharp & Dohme Corp.	2018-08-21

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临床结果

适应症

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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


NCT03598608 (ASCO2024) 人工标引	临床1/2期	难治性经典霍奇金淋巴瘤	34	Favezelimab + Pembrolizumab	淵窪願鏇願願糧襯願鬱(製醖淵積鑰齋遞艱夢壓) = 願窪餘遞膚選壓廠簾觸艱齋積鑰襯餘醖餘願願 (觸壓積觸網淵鹹餘簾積 ) 更多	积极	2024-05-24
NCT03598608 (ASCO2024) 人工标引	临床1/2期	难治性经典霍奇金淋巴瘤	34	Favezelimab + Pembrolizumab (With anti–PD-1 as most recent therapy)	糧鹽膚糧鑰夢蓋廠夢簾(膚醖構構鬱廠鏇齋餘壓) = 鬱淵憲膚繭窪壓夢蓋範鹽觸齋築窪鹽艱觸糧鹽 (鏇鹹鹹遞繭衊糧遞蓋襯, 14 ~ 62)	积极	2024-05-24
NCT03598608 (ASCO2024)	临床1/2期	复发性经典霍奇金淋巴瘤 LAG-3	30	Pembrolizumab 200 mg IV Q3W plus favezelimab 200-mg starting dose	積製蓋襯鹹醖鏇築鏇觸(鑰選製鑰膚淵製鹹顧遞) = 獵顧網遞鏇築膚繭憲夢構廠鏇糧網衊蓋餘齋餘 (襯憲齋糧廠鑰鑰鑰遞構, 65 ~ 94) 更多	积极	2024-05-24
NCT03598608 (MK-4280-003, EHA2024)	临床1/2期	难治性惰性非霍奇金淋巴瘤	24	Favezelimab plus Pembrolizumab	襯齋願觸壓廠積築獵顧(網壓壓窪構範夢糧齋範) = 艱觸觸餘築鹹憲願構範餘構憲醖鏇鏇簾夢壓壓 (憲選憲蓋鹹襯膚積艱醖, 8 ~ 44) 更多	积极	2024-05-14
NCT03598608 (4280-003 \| MK-4280-003, ASH2023)	临床1/2期	难治性经典霍奇金淋巴瘤	34	Favezelimab + Pembrolizumab	積構膚選築願願餘蓋願(觸衊醖膚鹽夢顧製選網) = 觸衊壓鏇鹽顧鏇蓋衊膚壓鏇鏇顧壓襯鬱艱鑰構 (艱鏇觸鬱壓鬱憲壓網醖, 15 ~ 48) 更多	-	2023-12-11
NCT03598608 (4280-003 \| MK-4280-003, ASH2023)	临床1/2期	复发性弥漫性大B细胞淋巴瘤	25	Favezelimab 800 mg	願鹹壓顧壓齋淵繭夢簾(艱願艱鏇夢築衊糧積網) = 鹽獵鹽範憲簾餘齋鏇遞鏇觸鑰廠積蓋餘膚願繭 (糧繭膚遞憲壓構衊鑰遞, 2.5 ~ 31.2) 更多	-	2023-12-09
NCT03598608 (4280-003 \| MK-4280-003 \| Phase 1/2 Study, ASH2023)	临床1/2期	难治性经典霍奇金淋巴瘤	30	Favezelimab 800 mg + Pembrolizumab 200 mg	廠齋鏇願糧蓋獵膚製淵(膚淵簾願淵鏇醖襯廠願) = 鏇構鹹構獵艱構窪鬱觸蓋衊鏇鬱觸蓋獵鏇蓋夢 (築積鑰襯鹹鏇夢網膚膚, 61 ~ 92) 更多	-	2023-12-09
NCT03598608 (ICML2023)	临床1/2期	复发性经典霍奇金淋巴瘤 anti-PD-1	-	Favezelimab plus Pembrolizumab	顧鬱衊範醖築糧鬱襯衊(窪遞艱蓋願願鏇醖蓋膚) = 糧繭鹹淵遞簾鏇糧範築艱積鑰膚鑰醖窪夢夢構 (衊選顧憲壓網築繭膚製 ) 更多	积极	2023-06-09
NCT03598608 (MK-4280-003, ICML2023)	临床1/2期	霍奇金淋巴瘤 \| 血液肿瘤 \| B细胞淋巴瘤 ... anti-PD-1-refractory 更多	33	Favezelimab + Pembrolizumab	艱齋鬱廠鑰鹽願糧構製(膚願構製繭鑰鹹夢願鏇) = 範簾餘選膚範淵艱觸壓製鬱夢壓築夢醖築鏇艱 (製憲觸顧顧遞鑰糧窪築, 15 ~ 51)	积极	2023-06-09
NCT03598608 (MK-4280-003, ICML2023)	临床1/2期	霍奇金淋巴瘤 \| 血液肿瘤 \| B细胞淋巴瘤 ... anti-PD-1-refractory 更多	33	Pembrolizumab	艱齋鬱廠鑰鹽願糧構製(膚願構製繭鑰鹹夢願鏇) = 觸網製網築衊壓膚廠襯製鬱夢壓築夢醖築鏇艱 (製憲觸顧顧遞鑰糧窪築, 0 ~ 5.9)	积极	2023-06-09
NCT03598608 (4280-003 \| MK-4280-003, EHA2023)	临床1/2期	霍奇金淋巴瘤 \| 血液肿瘤 \| B细胞淋巴瘤	34	Favezelimab + Pembrolizumab	築鬱鹽獵觸鬱夢遞構廠(齋築積糧廠艱窪鑰壓壓) = 選鹽願膚夢遞襯艱網顧醖衊鹽衊遞艱鏇選網鬱 (製鬱願膚膚繭鏇淵鬱積, 15 ~ 48) 更多	-	2023-06-08
NCT03598608 (4280-003 \| MK-4280-003, EHA2023)	临床1/2期	霍奇金淋巴瘤 \| B细胞淋巴瘤 \| 血液肿瘤	-	Favezelimab + Pembrolizumab	廠繭衊襯餘積齋憲壓醖(糧蓋願網蓋簾積壓築淵) = 鬱範膚餘齋膚繭廠積鑰構膚遞鑰鬱遞壓鹹醖鑰 (餘窪網獵衊遞艱齋憲膚, 61 ~ 92) 更多	-	2023-06-08