The purpose of this study is to evaluate evorpacept with anti-cancer therapies in advanced/metastatic malignancies. The study is comprised of the following substudies:
* Metastatic HER2+ breast cancer (MBC) - single-arm substudy evaluating the efficacy, safety, and tolerability of evorpacept in combination with trastuzumab and chemotherapy in participants with HER2-positive metastatic breast cancer who have previously received trastuzumab-deruxtecan. This substudy is actively recruiting.
* Metastatic colorectal cancer (CRC) - dose escalation phase to evaluate evorpacept in combination with other drugs. This substudy is not recruiting.
* Recurrent/metastatic head and neck cancer (HNSCC) - dose escalation phase to evaluate evorpacept in combination with other drugs. This substudy is not recruiting.

开始日期2025-04-28

申办/合作机构

ALX Oncology, Inc.

NCT05787639

/ Recruiting临床2期IIT

Neoadjuvant Radiation and Evorpacept (ALX148) in Combination With Pembrolizumab In Patients With Previously Untreated Locally Advanced, Resectable, HPVOPC (Human Papilloma Virus Oropharynx Cancer)

The majority of head and neck cancer patients do not respond to immunotherapies, and clinical responses are often not durable. However, targeting tumors with stereotactic radiation in combination with immunotherapy while sparing draining lymphatics enhances anticancer immunity, resulting in dramatic response in HPV (Human Papilloma Virus) virus related cancers of the throat. This trial will leverage targeted tumor radiation and immunotherapy in advance of standard surgical therapy to improve the response of HPV (Human Papilloma Virus) throat cancer to radiation and immunotherapy.

开始日期2024-02-20

申办/合作机构

University of California San Diego

NCT05467670

/ Recruiting临床2期IIT

Safety and Efficacy of Anti-CD47, ALX148 in Combination with Liposomal Doxorubicin and Pembrolizumab in Patients with Recurrent Platinum-resistant Ovarian Cancer: Phase II Study

Immunotherapy with immune checkpoint inhibitors, including pembrolizumab, have emerged as a promising option in several solid cancers with durable effect and low toxicity profile. However, the benefit is limited to smaller subset of solid tumors. This trial involves the enhancement of current immune checkpoint-based immunotherapy with ALX148, an agent that inhibits CD47 (a trans-membrane protein that is highly expressed on the surface of many solid tumors as compared to normal cells).

开始日期2023-03-30

申办/合作机构

University of Pittsburgh

[+2]

100 项与 Evorpacept 相关的临床结果

登录后查看更多信息

100 项与 Evorpacept 相关的转化医学

登录后查看更多信息

100 项与 Evorpacept 相关的专利（医药）

登录后查看更多信息

项与 Evorpacept 相关的文献（医药）

2024-07-01·CURRENT OPINION IN ONCOLOGY

State of the art and upcoming trends in HER2-directed therapies in gastrointestinal malignancies

Review

作者: Lee, Jaeyop ; Ku, Geoffrey

Purpose of review:

This review critically evaluates the evolution and current status of human epidermal growth factor receptor 2 (HER2)-directed therapies in upper gastrointestinal (GI) malignancies, a timely and relevant inquiry given the dynamic shifts in therapeutic strategies over the past decade. Initial enthusiasm following the Trastuzumab for Gastric Cancer (ToGA) study's demonstration of trastuzumab's efficacy, however, encountered hurdles due to subsequent trials showing limited progress, underscoring the necessity for a reevaluation of therapeutic approaches and the exploration of novel agents.

Recent findings:

The review highlights significant breakthroughs in the form of immune checkpoint inhibitors and innovative therapeutic technologies, which have redefined treatment paradigms and shown promising efficacy in HER2-positive cases. Emerging treatments such as trastuzumab deruxtecan (T-DXd), zanidatamab and evorpacept further illustrate the ongoing efforts to leverage unique mechanisms of action for improved HER2-positive antitumor activity.

Summary:

The advancements in HER2-directed therapies underscore a pivotal era in the management of upper GI malignancies. These developments not only reflect the profound impact of integrating novel therapeutic combinations but also highlight the critical role of ongoing research in overcoming resistance mechanisms and tailoring treatment to individual disease profiles.

2020-04-01·Seminars in oncology3区 · 医学

Just eat it: A review of CD47 and SIRP-α antagonism

3区 · 医学

Review

作者: Oronsky, Bryan ; Reid, Tony ; Carter, Corey ; Knox, Susan J ; Brinkhaus, Franck

The mammalian immune system consists of two distinct arms, nonspecific innate and more specific adaptive, with the innate immune response as the first line of defense and protection, which primes and amplifies subsequent adaptive responses. On the basis of this binary immune interplay, stimulation of T cells through checkpoint inhibitors (CIs), which bypasses innate involvement, seems likely to engender suboptimal or incomplete anticancer immunity, given that the successful induction of effect or responses depends on two-way innate/adaptive coordination. Indeed, the majority of patients-70%-80%, do not respond to CIs, which is potentially problematic if access to more optimal standard therapies is withheld or delayed in favor of ineffective or only marginally effective anti-PD-1/PD-L1 treatment. Therefore, stimulation of the innate immune response in combination with CIs (or other inducers of T cell cytotoxicity) has the potential to make the immune system "whole" and thereby to enhance and broaden the anti-tumor activity of PD-1/PD-L1 inhibitors for example, in relatively nonimmunogenic or "cold" tumor types. A critical innate macrophage immune checkpoint and druggable target is the antiphagocytic and "marker of self" CD47-SIRPα pathway, which is co-opted by cancer cells to mediate escape from immune-mediated clearance and checkpoint inhibition. This review summarizes the status of key CD47 antagonists in clinical trials, including the biologics, Hu5F9-G4 (5F9), TTI-621, and ALX148, as well as the small molecule, RRx-001, now in a Phase 3 clinical trial, which has not been previously included in CD47-SIRPα reviews focused on biologics. Hu5F9-G4 (5F9), TTI-621, ALX148, and RRx-001 are chosen as compounds with potentially promising data that have advanced the farthest in clinical development.

2018-11-01·Blood reviews2区 · 医学

Blocking “don't eat me” signal of CD47-SIRPα in hematological malignancies, an in-depth review

2区 · 医学

Review

作者: Montfort, William R ; Anwer, Faiz ; Carew, Jennifer S ; Persky, Daniel ; Hua, Anh B ; Riaz, Irbaz Bin ; Khalid, Muhammad Umar ; Russ, Atlantis ; Rahman, Bushra ; Nawrocki, Steffan T

Hematological malignancies express high levels of CD47 as a mechanism of immune evasion. CD47-SIRPα triggers a cascade of events that inhibit phagocytosis. Preclinical research supports several models of antibody-mediated blockade of CD47-SIRPα resulting in cell death signaling, phagocytosis of cells bearing stress signals, and priming of tumor-specific T cell responses. Four different antibody molecules designed to target the CD47-SIRPα interaction in malignancy are currently being studied in clinical trials: Hu5F9-G4, CC-90002, TTI-621, and ALX-148. Hu5F9-G4, a humanized anti-CD47 blocking antibody is currently being studied in four different Phase I trials. These studies may lay the groundwork for therapeutic bispecific antibodies. Bispecific antibody (CD20-CD47SL) fusion of anti-CD20 (Rituximab) and anti-CD47 also demonstrated a synergistic effect against lymphoma in preclinical models. This review summarizes the large body of preclinical evidence and emerging clinical data supporting the use of antibodies designed to target the CD47-SIRPα interaction in leukemia, lymphoma and multiple myeloma.

192

项与 Evorpacept 相关的新闻（医药）

2026-01-08

·ir.alxoncology.com

ALX Oncology Advances Separate Clinical Trials Evaluating Investigational CD47-Inhibitor Evorpacept and Novel EGFR-Targeted Antibody-Drug Conjugate ALX2004

- First patient dosed in Phase 2 ASPEN-09-Breast trial evaluating evorpacept in combination with trastuzumab and physician’s choice of chemotherapy in HER2-positive metastatic breast cancer; interim analysis anticipated Q3 2026 – - Third dose cohort initiated in Phase 1 trial of ALX 2004; study remains on track to provide initial safety data in 1H 2026 - SOUTH SAN FRANCISCO, Calif., Jan. 08, 2026 (GLOBE NEWSWIRE) -- ALX Oncology Holdings Inc. ("ALX Oncology," Nasdaq: ALXO), a clinical-stage biotechnology company advancing a pipeline of novel therapies designed to treat cancer and extend patients’ lives, announced that the first patient has been dosed in the Company’s Phase 2 ASPEN-09-Breast trial evaluating its investigational CD47-inhibitor evorpacept. This trial will evaluate the combination of evorpacept with trastuzumab and physicians’ choice of chemotherapy in patients with HER2-positive metastatic breast cancer whose disease has progressed after ENHERTU® (T-DXd). Additionally, after successfully clearing the second dose cohort, the Phase 1 trial evaluating the Company’s epidermal growth factor receptor (EGFR)-targeted antibody-drug conjugate (ADC) ALX2004 for the treatment of EGFR-expressing solid tumors has begun enrolling patients in the third dose cohort at 4mg/kg. No dose-limiting toxicities were observed in the prior two dose cohorts. "We are extremely pleased with the progress we are making on these clinical trials," said Jason Lettmann, Chief Executive Officer at ALX Oncology. "We believe both evorpacept and ALX2004 have the potential to fill significant gaps in the standard of care for many types of cancer." Evorpacept is the first CD47 inhibitor to show substantial tumor response and a well-tolerated safety profile in a randomized trial. Data from this prior gastric cancer trial, ASPEN-06, show that evorpacept demonstrated benefit across all efficacy parameters in patients with HER2-positive disease and high CD47 expression levels. Research has demonstrated that increased CD47 expression is correlated with poor patient outcomes in many tumor types, including breast cancer. The Phase 2 ASPEN-09-Breast clinical trial (NCT07007559) is a single-arm, open-label, multicenter study evaluating evorpacept plus trastuzumab and physicians’ choice of chemotherapy in 80 patients with HER2-positive breast cancer previously treated with ENHERTU® (fam-trastuzumab deruxtecan-nxki), which was recently approved as first-line therapy. The trial will utilize participants’ CD47 expression levels as a biomarker to assess responses. The primary endpoint of the trial is overall response rate (ORR) in patients who are confirmed HER2 positive by circulating tumor DNA (ctDNA). Key secondary endpoints are ORR in the HER2 ctDNA+ subpopulation by level of CD47 expression, clinical benefit rate (CBR), duration of response (DOR), progression-free survival (PFS) and overall survival (OS), and safety. ORR in the HER2 ctDNA-negative subpopulation is an exploratory endpoint. ALX Oncology anticipates sharing interim data from the trial in Q3 2026. The ALX2004 Phase 1 clinical trial (NCT07085091) is a first-in-human, open-label, multicenter trial evaluating ALX2004 in participants with advanced or metastatic select EGFR-expressing solid tumors. The study consists of a Phase 1a dose escalation portion followed by optional dose exploration, and a Phase 1b dose expansion. The dose escalation portion of the trial is enrolling patients with previously treated advanced or metastatic non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), esophageal squamous cell carcinoma (ESCC) and colorectal cancer (CRC). "Preclinical data suggest that ALX2004 has the potential to overcome the toxicity challenges associated with earlier generation EGFR-targeted ADCs," said Lettmann. "It is encouraging that, after clearing the second dose cohort in our Phase 1 trial at 2mg/kg, we are able to double the dosage to 4mg/kg in the third cohort." ALX Oncology expects to provide an initial safety update from the Phase 1 ALX2004 trial during 1H 2026. About ALX Oncology ALX Oncology (Nasdaq: ALXO) is a clinical-stage biotechnology company advancing a pipeline of novel therapies designed to treat cancer and extend patients’ lives. ALX Oncology’s lead therapeutic candidate, evorpacept, has demonstrated potential to serve as a cornerstone therapy upon which the future of immuno-oncology can be built. Evorpacept is currently being evaluated across multiple ongoing clinical trials in a wide range of cancer indications. ALX Oncology’s second pipeline candidate, ALX2004, is a novel EGFR-targeted antibody-drug conjugate with a differentiated mechanism of action. A Phase 1, dose-escalation trial of ALX2004 is ongoing in patients with EGFR-expressing solid tumors. Cautionary Note Regarding Forward-Looking Statements This press release contains forward-looking statements that involve substantial risks and uncertainties. Forward-looking statements include statements regarding future results of operations and financial position, business strategy, product candidates, planned preclinical studies and clinical trials, results of clinical trials, research and development costs, regulatory approvals, timing and likelihood of success, plans and objects of management for future operations, as well as statements regarding industry trends. Such forward-looking statements are based on ALX Oncology’s beliefs and assumptions and on information currently available to it on the date of this press release. Forward-looking statements may involve known and unknown risks, uncertainties and other factors that may cause ALX Oncology’s actual results, performance or achievements to be materially different from those expressed or implied by the forward-looking statements. These and other risks are described more fully in ALX Oncology’s filings with the Securities and Exchange Commission (SEC), including ALX Oncology’s Annual Reports on Form 10-K, Quarterly Reports on Form 10-Q and other documents ALX Oncology files with the SEC from time to time. Except to the extent required by law, ALX Oncology undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made. More information is available at www.alxoncology.com and on LinkedIn @ALX Oncology. Investor Relations Contact: Elhan Webb, CFA, IR Consultant ewebb@alxoncology.com Media Contact: Michele Parisi, SparkPoint Healthcare Communications mparisi@sparkpointpr.com (925) 864-5028

临床1期抗体药物偶联物临床2期上市批准免疫疗法

2026-01-07

·有驾

抗癌新突破！CD47靶点药物如何破解“别吃我”信号难题

科学界历经十余年攻坚，曾经因血液毒性险些被放弃的CD47靶点，如今正成为肿瘤免疫治疗的新希望。2009年，斯坦福大学Irving Weissman教授团队在《细胞》杂志上发表两项开创性研究，首次揭示癌细胞通过表面高表达的CD47蛋白与巨噬细胞表面的SIRPα结合，发出“别吃我”信号，从而逃避免疫系统的吞噬清除。这一发现点燃了科学界对CD47靶点的研发热情。CD47作为肿瘤免疫治疗的新星靶点，其发展历程却充满挑战与突破。从最初因血液毒性险些被放弃，到如今第三代技术带来新的希望，CD47靶向药物的研发历程堪称一部创新药发展的缩影。 01 靶点机制：癌细胞如何利用“别吃我”信号逃避免疫监视 CD47是一种广泛表达于多种细胞表面的跨膜糖蛋白，也被称为整合素相关蛋白（IAP）。它通过与免疫细胞上的信号调节蛋白α（SIRPα）结合，发出“别吃我”的信号，抑制巨噬细胞的吞噬作用，从而保护健康细胞不被免疫系统破坏。研究表明，大多数肿瘤细胞均存在CD47的过度表达，且CD47高表达与患者不良预后密切相关。肿瘤细胞利用这一机制，伪装成“自己人”，逃避免疫系统的攻击。CD47靶向药物的核心作用机制是通过阻断CD47-SIRPα信号通路，解除肿瘤细胞的“别吃我”信号，同时通过抗体Fc段介导的效应功能，如抗体依赖性细胞吞噬作用（ADCP），激活巨噬细胞杀伤肿瘤细胞。 02 发展历程：CD47靶点药物研发的三代技术演进第一代CD47抗体：血液毒性成绊脚石 CD47药物研发初期，最大的挑战是红细胞表面也大量表达CD47，导致抗体在攻击肿瘤细胞的同时也会误伤红细胞，引起严重贫血和血小板减少等副作用。最具代表性的第一代CD47抗体是吉利德公司的Magrolimab（原Hu5F9-G4）。为解决血液毒性问题，研究人员采用了预激给药策略：先给予低剂量（1mg/kg）清除衰老红细胞，刺激新红细胞生成，再逐步增加剂量。这一策略在早期临床试验中显示出 promise。2019年美国血液学会（ASH）年会上公布的数据显示，Magrolimab与阿扎胞苷联合治疗骨髓增生异常综合征（MDS）和急性髓系白血病（AML）患者，客观缓解率（ORR）分别高达92%和64%。然而，2023年，Magrolimab在三期临床研究中因疗效不足接连受挫，吉利德终止了其针对MDS和AML的多项临床试验。第二代CD47抗体：优化设计降低毒性第二代CD47抗体致力于通过分子优化减少与红细胞的结合。信达生物的IBI188和ALX Oncology的Evorpacept（ALX-148）是这一代代表作品。Evorpacept采用Fc结构域灭活策略，完全消除了Fc效应功能，虽然避免了血液毒性，但单药治疗效果不佳，必须依赖联合用药。2023年，ALX Oncology宣布终止Evorpacept治疗MDS和AML的临床研究，主因疗效不足。第三代CD47抗体：精准靶向突破毒性瓶颈第三代CD47抗体通过精准靶向技术，实现了对肿瘤细胞的特异性识别，同时最小化对红细胞的影响。天境生物的开发团队采用噬菌体展示技术筛选CD47抗体，并通过负向筛选找到与红细胞低亲和力的抗体。在约200个CD47结合阳性克隆中，他们发现了唯一一个同时具有高肿瘤结合力和低红细胞结合力的抗体——来佐利单抗（lemzoparlimab，TJC4）。来佐利单抗的独特之处在于它能识别CD47的特殊表位，该表位在红细胞上因糖基化修饰而无法充分暴露，从而大大降低了与红细胞的结合能力。临床数据显示，来佐利单抗无需预激给药，在高达30mg/kg的剂量下仍表现出良好安全性。康方生物的AK117则采用不同的策略，通过在IgG4抗体基础上改造Fc结构，调整CD47结合的表位及复合物角度，减少红细胞凝集现象。 03 研究意义：CD47靶点为何成为必争之地 CD47靶点被誉为继PD-1/PD-L1之后最具潜力的肿瘤免疫治疗靶点，其研究意义重大。CD47信号通路在多种血液肿瘤和实体瘤中发挥关键作用。特别是在目前治疗选择有限的MDS和AML领域，CD47靶向药物展现出巨大潜力。CD47靶点的重要性还体现在其与现有疗法的协同作用。临床前研究显示，CD47抗体与阿扎胞苷联用可产生协同抗肿瘤效应。阿扎胞苷可增强“吃我”信号，而CD47抗体则阻断“别吃我”信号，共同增强对肿瘤细胞的吞噬作用。此外，CD47靶向药物在解决肿瘤耐药性问题方面也展现出潜力。研究表明，CD47在肿瘤干细胞上高表达，这可能是导致肿瘤复发和治疗抵抗的重要原因之一。靶向CD47有望消除肿瘤干细胞，从而防止肿瘤复发。 04 未来发展方向：联合治疗与创新策略尽管CD47靶点研发遭遇挫折，但未来仍有多条路径可能引领这一领域走向成功。联合治疗策略 CD47靶向药物与其它疗法的联合应用是主要发展方向。目前研究的联合策略包括： (1) 与化疗药物联用：如与阿扎胞苷、维奈克拉等联合治疗血液肿瘤 (2) 与免疫检查点抑制剂联用：如与PD-1/PD-L1抗体联合，同时激活先天性和适应性免疫 (3) 与靶向药物联用：如与CD20抗体、HER2抗体等联合应用 ALX Oncology的Evorpacept在联合治疗方面已取得初步成功。其与曲妥珠单抗、雷莫西尤单抗和紫杉醇联用治疗HER2阳性胃癌/胃食管结合部癌的二期研究显示，客观缓解率达到52%，显著优于对照组的22%。双特异性抗体开发双特异性抗体是CD47靶点发展的另一重要方向。天境生物开发的TJ-L1C4（靶向PD-L1和CD47）和TJ-C4GM（靶向CD47和GM-CSF）等双特异性抗体，可同时阻断多个免疫抑制信号，增强抗肿瘤效果。实体瘤治疗探索虽然CD47抗体在血液肿瘤中效果更为明确，但实体瘤才是CD47靶向药物的终极目标。目前，多个CD47靶向药物已在实体瘤中展开临床研究。例如，Evorpacept联合帕博利珠单抗一线治疗头颈部鳞状细胞癌的客观缓解率达到38.5%。这些早期数据为CD47靶向药物在实体瘤中的应用提供了初步证据。创新分子设计未来的CD47靶向药物将更加注重分子设计的创新。宜明昂科开发的IMM01采用SIRPα-Fc融合蛋白设计，选择具有较强Fc效应功能的IgG1亚型，同时通过改造避免与红细胞结合。IMM01已在中国进入三期临床试验，早期数据显示其在不使用低初始剂量的情况下，联合阿扎胞苷治疗较高危MDS患者的客观缓解率达到64.7%。据医药魔方NextPharma数据库显示，全球共有65款CD47靶点药物进入临床阶段，其中超过半数来自中国药企。天境生物、康方生物、宜明昂科等国内企业的创新研发，正使中国在CD47靶点领域跻身世界前列。CD47靶向药物的研发历程印证了创新药开发的普遍规律：真正的突破往往源于对失败经验的深刻理解。随着对CD47生物学机制的深入理解和药物技术的持续创新，CD47靶点有望在未来五年内迎来重要突破，为肿瘤患者提供新的治疗选择。科学界历经十余年攻坚，曾经因血液毒性险些被放弃的CD47靶点，如今正迎来新的曙光。文章来源于网络、如有侵权请联系作者删除

2026-01-06

·生物制药小编

CD47如何逆袭？盘点2025年6项CD47疗法最新临床研究数据

如果说制药界也有“意难平”，CD47绝对高居榜单前列。曾经，它是免疫肿瘤领域的重磅靶点，而伴随着血液毒性或疗效不足等原因造成的临床试验接连失利，先驱Arch Oncology、吉利德、辉瑞、艾伯维等公司相继离场。初代CD47药物失败的故事，源于阻断癌细胞CD47的“别吃我”信号时，把红细胞、血小板上的CD47信号也阻断了，好比炸了整条街，敌人没了，但路上行人也遭了殃；如果火力不足，就会竹篮打水一场空。然而，故事并未终结。CD47靶向先天免疫（巨噬细胞）的机制，与PD-1/PD-L1靶向适应性免疫（T细胞）有本质不同，这为大量PD-1/PD-L1疗法无效的“冷肿瘤”患者提供了全新的希望。因此，如何“精巧调控”，在确保安全的前提下最大化发挥CD47通路作用就成了关键。转折正在发生。2025年，一批新一代CD47疗法，在ASCO、ESMO等国际大会上公布了令人瞩目的早期临床数据，初步证明了在显著降低甚至规避血液毒性的同时，能够激发可观的抗肿瘤活性。下面，小编就为读者盘点2025年6款CD47靶向疗法及其临床数据，看它们如何逆袭新生。单抗进阶优化：选择性靶向CD47，与肿瘤细胞高效力结合的同时，避免血液毒性。代表产品：ImmuneOncia Therapeutics | IMC-002 (CD47单抗) 在2025年ASCO美国临床肿瘤学会年会上，ImmuneOncia Therapeutics公布了其新一代CD47抗体IMC-002联合仑伐替尼治疗晚期肝细胞癌（HCC）患者的1b期临床试验中期结果。在这项剂量扩展阶段研究，IMC-002展现出良好的安全性特征，未报告中性粒细胞减少症或血小板减少症病例。13例患者中有2例（15%）出现轻度贫血，96%的不良事件为1-2级，且主要发生在首个治疗周期。多数患者既往接受过抗PD-(L)1治疗（11例），且ECOG体能状态评分为1分（9例）。在10例可评估疗效的患者中，客观缓解率（ORR）为30%，疾病控制率（DCR）为70%。中位疾病进展时间（TTP）为8.3个月。小编点评：根据ImmuneOncia Therapeutics披露的信息，IMC-002具备独特的结合构象与抗原表位，可最大限度地减少与红细胞的结合，是其解决血液毒性的主要方式。 SIRPα-Fc融合蛋白：使用SIRPα的CD47结合域融合蛋白，阻断CD47信号通路代表产品1：ALX Oncology | Evorpacept（SIRPα-Fc融合蛋白）在2025年ASCO GI美国临床肿瘤学会胃肠道肿瘤研讨会上，ALX Oncology公布了Evorpacept（Evo）与标准曲妥珠单抗（T）、雷莫西尤单抗（R）和紫杉醇（P）联合治疗HER2阳性胃癌患者的ASPEN-06研究随机II期部分的最终分析。在全部随机化人群（N=127）中，Evo-TRP组的ORR为40.3%，对照组（TRP）为26.6%。Evo-TRP组的ORR在探索性分析中较TRP组显示出13.7%的显著增加（P=0.028）。Evo-TRP和TRP的中位缓解持续时间（DOR）分别为15.7个月和7.6个月。在预先指定的经抗HER2治疗后的新鲜肿瘤活检组织中检测为HER2阳性的患者群体中（N=48），Evo-TRP的ORR为54.8%，相较于TRP组的ORR高出31.7%（探索性分析中P=0.004）。Evo-TRP组耐受性良好，其安全性特征与既往的研究经验一致。小编点评：根据ALX Oncology披露的信息，Evorpacept的Fc域经工程化突变失活，消除了对Fcγ受体的结合作用，是其解决血液毒性的主要方式。代表产品2：汉康生技 | HCB101（SIRPα-Fc融合蛋白）在2025年ESMO IO免疫肿瘤学大会上，汉康生技公布了HCB101的最新临床试验数据（数据截至2025年10月）。在单药治疗研究中，在12个剂量队列中（最高至36 mg/kg，每周一次）均显示出对血细胞影响轻微的特性。无出血事件或免疫相关毒性：大多数治疗相关不良事件为1-2级。疗效方面，已展现抗肿瘤活性，包括2例确认的部分缓解：一例为头颈鳞状细胞癌，肿瘤缩小约42%，缓解持续≥32周；1例为边缘区淋巴瘤，肿瘤缩小约89%，缓解持续≥16周。在与标准治疗的联合治疗研究中，耐受性良好，无新的安全性信号，血细胞减少完全归因于化疗，而非HCB101。二线胃癌中：客观缓解率达58.3%（7/12），疾病控制率达100%，肿瘤最大缩小幅度达-78.2%。一线HER2阳性胃癌中：客观缓解率为33%（1/3）。一线三阴性乳腺癌中：客观缓解率为33%（2/6），疾病控制率达100%。小编点评：根据汉康生技披露的信息，HCB101的SIRPα结构域引入了利用AI引导的结构建模发现的关键突变点，大幅降低与红细胞CD47的结合力，同时保留对肿瘤细胞CD47的高亲和力，是其解决血液毒性的主要方式。双抗精准定位：一边结合肿瘤特异靶点，另一边结合CD47，相当于给巨噬细胞装了GPS，指哪打哪。代表产品1：Light Chain Bioscience | NI-1801（CD47 x MSLN双抗）在2025年ESMO欧洲肿瘤内科年会上，Light Chain Bioscience公开了NI-1801单药治疗和与帕博利珠单抗联合治疗在既往接受过至少4线治疗且表达间皮素的铂类耐药上皮性卵巢癌（PROC）患者中的数据（截至2025 年 5 月 12 日）。在单药治疗中，600 mg和900 mg剂量组共治疗21例PROC患者中，客观缓解率为5%，1年OS率为35.3%。在联合帕博利珠单抗治疗中，600 mg和900 mg剂量组共治疗21例PROC患者中，客观缓解率为28.5%，1年OS率为75.2%，未成熟的9个月PFS rate为32.7%。与标准治疗相比，在至少接受过一线化疗的铂类耐药卵巢癌患者群体中，标准化疗的中位总生存期在9至12个月之间，NI-1801展现出显著的协同增效潜力。小编点评：根据Light Chain Bioscience披露的信息，NI-1801的抗CD47单臂采用低亲和力，抗MSLN单臂采用高亲和力，以加强与MSLN阳性肿瘤细胞的结合，是其解决血液毒性的主要方式。代表产品2：宜明昂科 | IMM0306（CD47×CD20双抗）在2025年第67届ASH美国血液学会年会上，宜明昂科公开了阿沐瑞芙普α（IMM0306）联合来那度胺治疗复发/难治性CD20阳性滤泡性淋巴瘤患者的I/II期临床研究数据（数据截至2025年7月10日）。该联合方案在既往接受过至少一线含抗CD20单抗治疗失败的患者中，II期34例疗效可评估患者的分析结果显示，客观缓解率（ORR）达91.2%，CR率高达67.6%（23/34），中位随访9.02个月，中位PFS尚未达到，6个月PFS率为91.2%（95%CI: 75.1-97.1）。在预后更差的抗CD20难治性亚组（18例）中，ORR仍达88.9%，CR率为66.7%。安全性总体可控且无细胞因子风暴风险。小编点评：根据宜明昂科披露的信息，IMM0306由CD20单克隆抗体与SIRPα的CD47结合域融合而成，IMM0306对CD20的亲和力高于CD47，因此可以优先与恶性B细胞上的CD20及CD47结合，减少了与正常细胞CD47靶点的结合，是其解决血液毒性的主要方式。双重免疫调节：SIRPα和4-1BBL融合蛋白，局部、有条件激活先天和适应性免疫反应。代表产品：KAHR Bio | DSP107（SIRPα和4-1BBL三聚体融合蛋白）在2025年ASCO美国临床肿瘤学会上，KAHR Bio报告了DSP107联合或不联合阿替利珠单抗在转移性微卫星稳定型结直肠癌患者的II期剂量扩展研究的结果。研究纳入既往接受过包括标准化疗±靶向抗体的二线治疗后进展的转移性/不可切除MSS CRC患者（n=50），被随机分配接受每周静脉输注DSP107（10 mg/kg/剂）单药治疗或联合阿替利珠单抗（1200 mg，每3周一次）。在接受DSP107单药治疗（n=19）和DSP107联合阿替利珠单抗治疗（n=21）疗效可评估患者中，中位总生存期（OS）尚未达到，截至2024年12月的生存期分别为7.6个月和14.6个月。在可评估患者中，疾病控制率（DCR）分别为26%（单药）和62%（联合），其中包括一名达到完全缓解（>2.5年）的患者，以及一名获得深度（靶病灶缩小86%）且持久（>16个月）部分缓解并伴有肺部和肝转移灶消失的患者。DSP107单药及联合阿替利珠单抗治疗耐受性良好，未观察到DLT。小编点评：根据KAHR披露的信息，DSP107在I期临床试验中（最高剂量探索至10 mg/kg）显示其具有出色的安全性，无血液学、肝脏或其他剂量限制性毒性；DSP107与红细胞结合微弱，可能归因于红细胞膜上CD47结构活动性有限，限制了DSP107中含有三个SIRPα结构域与红细胞表面CD47结合。结语 CD47的故事，在2025年被改写了叙事基调。这条一度被冰封的赛道，凭借分子工程学的精巧智慧已然解冻。以上6项临床数据，不仅是6份成绩单，更是6种破解“CD47悖论”的路径宣言： IMC-002用优化抗体证明，血液毒性并非不可逾越，安全窗可以被显著拓宽。 Evorpacept和HCB101则展示了SIRPα-Fc融合蛋白策略的潜力，在与化疗、靶向药的联用中不断验证协同价值。 NI-1801和IMM0306代表的双抗模式，将疗效精准导向肿瘤，带来惊喜。 DSP107则探索了更复杂的双重免疫调节，为创新药研发带来了新的可能性。这些数据共同指向一个核心结论：CD47的研发竞赛，已从“能否成药”的生死质疑，全面进入 “谁更优、更精准、更具协同价值”的角逐。展望未来，CD47的逆袭之路将取决于两个关键：一是这些明星分子在更大规模的II期临床试验中能否展示彻底解决血液毒性的问题；二是不同技术路径（如单抗、双抗、融合蛋白）将在不同肿瘤适应症中展开一场关于疗效、安全性管理和联合治疗潜力的综合竞争，谁能脱颖而出。对于患者而言，这意味着针对“冷肿瘤”和PD-1/PD-L1耐药患者，一个全新的先天免疫治疗工具箱正在成型。对于行业与投资者，CD47的故事则从一个关于“靶点风险”的警示案例，演变为一个关于“价值重塑”的契机：真正的赢家，将是那些能用最终临床数据，将这份“逆袭”的潜力转化为真正患者获益的智者。

ASCO会议临床结果免疫疗法临床1期临床2期

100 项与 Evorpacept 相关的药物交易

登录后查看更多信息

外链

KEGG	Wiki	ATC	Drug Bank
D12193	-	-	-

研发状态

10 条进展最快的记录,

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
HER2表达胃腺癌	临床3期	美国	ALX Oncology, Inc.	2022-01-15
HER2表达胃腺癌	临床3期	美国	Eli Lilly & Co.	2022-01-15
HER2表达胃腺癌	临床3期	日本	Eli Lilly & Co.	2022-01-15
HER2表达胃腺癌	临床3期	日本	ALX Oncology, Inc.	2022-01-15
HER2表达胃腺癌	临床3期	澳大利亚	Eli Lilly & Co.	2022-01-15
HER2表达胃腺癌	临床3期	澳大利亚	ALX Oncology, Inc.	2022-01-15
HER2表达胃腺癌	临床3期	比利时	Eli Lilly & Co.	2022-01-15
HER2表达胃腺癌	临床3期	比利时	ALX Oncology, Inc.	2022-01-15
HER2表达胃腺癌	临床3期	捷克	ALX Oncology, Inc.	2022-01-15
HER2表达胃腺癌	临床3期	捷克	Eli Lilly & Co.	2022-01-15

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT05025800 (ASH2025)	临床2期	惰性B细胞非霍奇金淋巴瘤一线	24	Evorpacept (ALX148) + Lenalidomide + Rituximab	糧壓構齋選獵願齋廠顧(壓醖構遞窪築艱遞積膚) = 壓艱構簾膚顧鹹範襯壓衊築選淵襯廠製艱廠獵 (觸蓋顧鬱積憲選鬱獵窪 ) 更多	积极	2025-12-06
NCT04675294 (ASPEN-03, ESMO2025)	临床2期	PD-L1阳性头颈部鳞状细胞癌 PD-L1 positive	181	Evorpacept (evo) + Pembrolizumab	憲鬱鬱憲製願願齋艱積(獵構繭憲築餘蓋壓範齋) = 餘壓糧衊觸艱襯糧齋醖鏇觸願憲鹽獵餘襯鹽艱 (鬱鹽鬱顧壓膚齋鑰餘製, 18.8 ~ 35.2)	不佳	2025-10-17
				Pembrolizumab	憲鬱鬱憲製願願齋艱積(獵構繭憲築餘蓋壓範齋) = 鏇網鏇鑰衊廠壓醖範築鏇觸願憲鹽獵餘襯鹽艱 (鬱鹽鬱顧壓膚齋鑰餘製 )
NCT04675333 (ASPEN-04, ESMO2025)	临床2期	复发性头颈部鳞状细胞癌	165	Evorpacept (evo) + Pembrolizumab + Chemotherapy	積餘簾鏇範遞窪衊壓積(範襯蓋構膚構鹹製簾衊) = 廠廠鹹鏇壓夢簾繭鹹齋簾膚鏇齋鏇蓋艱積齋醖 (膚範鏇願夢範蓋淵構築, 28.2 ~ 47.0)	不佳	2025-10-17
				Pembrolizumab + Chemotherapy	積餘簾鏇範遞窪衊壓積(範襯蓋構膚構鹹製簾衊) = 鹹齋積憲積鏇範繭蓋蓋簾膚鏇齋鏇蓋艱積齋醖 (膚範鏇願夢範蓋淵構築, 32.0 ~ 59.4)
ASPEN-09-03 (ESMO2025)	临床2期	HER2阳性转移性乳腺癌 HER2-positive	80	Evorpacept + Trastuzumab + Chemotherapy	憲艱製遞鹹鹹襯憲積窪(顧憲糧艱齋鹽艱壓簾壓) = 襯餘膚鑰鏇鏇鬱鏇積鏇夢遞醖簾蓋衊蓋鏇憲鏇 (願糧願夢鏇構廠壓遞製 )	积极	2025-10-17
NCT05787639 (Phase II trial of neoadjuvant SBRT followed by combination evorpacept/pembrolizumab in HPV+ HNSCC, ASCO2025)	临床2期	头颈部鳞状细胞癌新辅助 HPV+	27	evorpacept (Neoadjuvant SBRT)	鹽夢範衊鏇膚鹹選醖繭(鹹遞艱蓋獵廠繭簾鹽網) = 廠鬱觸憲積蓋選觸鑰鬱衊獵顧鬱範衊廠夢壓夢 (糧顧獵選窪襯築窪願築 )	积极	2025-05-30
NCT05025800 (AACR2025) 人工标引	临床1期	非霍奇金淋巴瘤	20	Evorpacept + lenalidomide + rituximab	艱觸鹽蓋鏇積淵獵鬱網(網築廠繭憲網簾願餘繭) = 夢範觸鏇膚繭廠顧艱糧鑰襯觸鹽顧鏇襯鏇願糧 (製膚選衊憲簾廠範獵鏇 ) 更多	积极	2025-04-29
NCT04675294 (ASPEN-03, Company_Website) 人工标引	临床2期	晚期头颈部鳞状细胞癌一线 PD-L1 Positive	-	Evorpacept + pembrolizumab	網窪餘膚襯艱餘繭醖膚(襯膚廠糧鑰鏇範壓襯憲) = Not Meet Primary Endpoints 窪淵繭糧膚選遞衊壓衊 (齋夢構醖簾觸獵壓製獵 ) 未达到	不佳	2025-04-25
				pembrolizumab
NCT04675333 (ASPEN-04, Company_Website) 人工标引	临床2期	晚期头颈部鳞状细胞癌	-	evorpacept + pembrolizumab + chemotherapy	願繭膚觸醖窪範鑰簾衊(襯膚網夢選築製艱網網) = Not Meet Primary Endpoints. 構範鏇網構壓壓醖顧壓 (獵願淵積蓋鹽網壓廠獵 ) 未达到	不佳	2025-04-25
				pembrolizumab + chemotherapy
NCT05002127 (ASPEN-06, ASCO_GI2025) 人工标引	临床2/3期	HER2阳性胃食管腺癌 \| HER2阳性胃癌 HER2+	127	EvorpaceptEvorpacept (ALX148) + Trastuzumab (T) + Ramucirumab (R) + Paclitaxel (P)	窪壓鹽範夢鬱鹽鏇襯壓(壓願糧繭鹽淵艱選襯淵) = 構鬱艱鹹顧願憲築獵築簾願築艱蓋鑰鏇壓餘餘 (鹹獵積淵蓋願願鹹觸遞 ) 更多	积极	2025-01-23
				Trastuzumab (T) + Ramucirumab (R) + Paclitaxel (P)	窪壓鹽範夢鬱鹽鏇襯壓(壓願糧繭鹽淵艱選襯淵) = 膚鏇艱齋範獵構鹹鏇簾簾願築艱蓋鑰鏇壓餘餘 (鹹獵積淵蓋願願鹹觸遞 ) 更多
NCT05002127 (ASPEN-06, Corporate Publications) 人工标引	临床2/3期	HER2阳性胃食管交界处癌 \| HER2阳性胃癌 HER2 Positive	127	Evorpacept + Trastuzumab + Ramucirumab + Paclitaxel	繭廠壓構構網齋構繭簾(衊遞鬱壓顧繭齋繭醖鹹) = 鹽構遞簾鹹觸築窪範艱淵鬱鑰遞繭壓鹹餘窪構 (繭獵襯顧膚築網夢艱糧, 29.0 ~ 54.4) 更多	积极	2025-01-23
				Trastuzumab + Ramucirumab + Paclitaxel	繭廠壓構構網齋構繭簾(衊遞鬱壓顧繭齋繭醖鹹) = 構壓鹹顧餘壓艱繭獵淵淵鬱鑰遞繭壓鹹餘窪構 (繭獵襯顧膚築網夢艱糧, 16.3 ~ 39.1) 更多