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]

NCT05868226

/ Recruiting临床1期

PRE-Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging And moLecular Analysis: A Phase I/Ib Platform Trial

I-SPY Phase I/Ib (I-SPY-P1) is an open-label, multisite platform study designed to evaluate single agents or combinations in a metastatic treatment setting that may be relevant for breast cancer patients with the overall goal of moving promising drug regimens into the I-SPY 2 SMART Design Trial (NCT01042379) and/or other oncology-based trials in a timely manner.

开始日期2023-02-15

申办/合作机构

Quantumleap Healthcare Collaborative

NCT05524545

/ Recruiting临床1期

A Phase 1, Open-label, Multicenter, Safety, Pharmacokinetic, Pharmacodynamic Study of ALX148 in Combination With Enfortumab Vedotin and/or Other Anticancer Therapies in Subjects With Urothelial Carcinoma (ASPEN-07)

AT148007 is a Phase 1, open-label, multicenter, safety, pharmacokinetic, pharmacodynamic study of ALX148 in combination with enfortumab vedotin and/or other anticancer therapies in subjects with urothelial carcinoma.

开始日期2022-11-02

申办/合作机构

ALX Oncology, Inc.

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 reviewThis 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 findingsThe 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.SummaryThe 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.

2024-01-01·Transfusion Medicine and Hemotherapy

Evorpacept-Induced Interference and Application of a Novel Mitigation Agent, Evo-NR, in Pretransfusion Testing

Article

作者: Kim, Tae Yeul ; Kim, Hyungsuk ; Cho, Duck ; Yoon, Eungjun

Introduction: Evorpacept is a CD47-blocking agent currently being developed for the treatment of various cancers. Interference by evorpacept in pretransfusion compatibility testing has been reported at limited plasma concentrations. Although various mitigation strategies have been proposed, none are practical. This in vitro study assessed evorpacept-induced interference at extended concentrations and investigated the capability of a novel mitigation agent, Evo-NR. Methods: Antibody screening tests were performed on evorpacept-spiked plasma with (anti-E and anti-Jka) or without alloantibodies at evorpacept concentrations up to 2,000 μg/mL using manual gel cards and automated analyzers. Evorpacept-coated red blood cells (RBCs) (rr [ce/ce], Fy[a+b−], S−s+) were tested by direct antiglobulin testing (DAT) and antigen typing using anti-Fyb and anti-S reagents at indirect antiglobulin testing (IAT) phase. Evo-NR was used to resolve the interference in plasma and RBC samples. Flow cytometry was used to assess the mitigation effects. Results: Evorpacept-spiked plasma showed panreactive interference in antibody screening tests using manual gel cards (2+ to 3+) and automated analyzers (4+). A carryover effect was also observed in the automated analyzers. The use of a 3- to 6-fold molar excess of Evo-NR effectively resolved the interference in the plasma and enabled accurate alloantibody identification. Although the reduction in evorpacept binding to RBCs was identified via flow cytometry, Evo-NR was incapable of resolving the serologic interference observed in DAT and antigen typing at IAT phase. Discussion: Evorpacept showed constant panreactivity and a carryover effect at high concentrations. Evo-NR successfully resolved the interference in the plasma samples and could be considered a practical and efficient mitigation solution. Implementation of Evo-NR has the potential to support RBC transfusion for patients undergoing evorpacept treatment.

2021-12-01·The Lancet Oncology1区 · 医学

Evorpacept alone and in combination with pembrolizumab or trastuzumab in patients with advanced solid tumours (ASPEN-01): a first-in-human, open-label, multicentre, phase 1 dose-escalation and dose-expansion study

1区 · 医学

Article

作者: Hong I Wan ; Yung-Jue Bang ; Patricia LoRusso ; Feng Jin ; Sophia S Randolph ; Hyun Cheol Chung ; Jaume Pons ; Pierre Squifflet ; Keun-Wook Lee ; Frank Stephen Hodi ; Wells A Messersmith ; Jeeyun Lee ; Justin F Gainor ; Won Seog Kim ; Nehal J Lakhani ; Tracy C Kuo ; Rafael Santana-Davila ; Laura Q M Chow ; Philip Fanning

BACKGROUNDBoth innate and adaptive immune responses are important components of anticancer immunity. The CD47-SIRPα interaction could represent an important pathway used by tumour cells to evade immune surveillance. We aimed to evaluate the safety, pharmacokinetics, pharmacodynamics, and anticancer activity of evorpacept (also known as ALX148), a high-affinity CD47-blocking protein with an inactive IgG Fc region in patients with solid tumours.METHODSWe did a first-in-human, open-label, multicentre, phase 1 dose-escalation and dose-expansion study at nine hospitals and one clinic in the USA and Korea. Eligible patients for the dose-escalation and safety lead-in phases were aged 18 years or older with histological or cytological diagnosis of advanced or metastatic solid tumours with no available standard therapy, measurable or unmeasurable disease according to the Response Evaluation Criteria in Solid Tumors version 1.1, and an Eastern Cooperative Oncology Group performance status score of 0 or 1. In the dose-escalation phase, which used a 3 + 3 design, patients received intravenous evorpacept at either 0·3, 1, 3, or 10 mg/kg once per week in 21-day cycles, or 30 mg/kg once every other week in 28-day cycles. In the safety lead-in phase, patients were given the maximum tolerable dose of evorpacept from the dose-escalation phase plus either intravenous pembrolizumab (200 mg administered once every 3 weeks) or intravenous trastuzumab (8 mg/kg loading dose followed by 6 mg/kg once every 3 weeks). In the dose-expansion phase, additional patients aged 18 years or older with second-line or later-line advanced malignancies were enrolled into three parallel cohorts: those with head and neck squamous cell carcinoma (HNSCC) and those with non-small-cell lung cancer (NSCLC) were given the maximum tolerated dose of evorpacept plus intravenous pembrolizumab (200 mg administered once every 3 weeks), and patients with HER2-positive gastric or gastroesophageal junction cancer were given the maximum tolerated dose of evorpacept plus intravenous trastuzumab (8 mg/kg loading dose followed by 6 mg/kg once every 3 weeks) until disease progression, voluntary withdrawal from the study, or unacceptable toxicity. The primary endpoint was the maximum tolerated dose of evorpacept administered as a single agent and in combination with pembrolizumab or trastuzumab, measured by the occurrence of dose-limiting toxicities during the first cycle, and was assessed in all patients who had received at least one dose of evorpacept. Secondary outcomes included the safety, tolerability, and antitumour activity of evorpacept, alone or in combination with pembrolizumab or trastuzumab. The primary outcome, safety, and tolerability were assessed in all patients who had received at least one dose of evorpacept, and antitumour activity was assessed in those who recieved at least one dose of study treatment and underwent at least one post-baseline tumor assessment. This trial is registered with ClinicalTrials.gov, NCT03013218.FINDINGSBetween March 6, 2017, and Feb 21, 2019, 110 patients received single-agent evorpacept (n=28), evorpacept plus pembrolizumab (n=52), or evorpacept plus trastuzumab (n=30), and were included in the safety analysis. Median follow-up was 29·1 months (95% CI not calculable [NC]-NC) in the single-agent cohort, 27·0 months (25·1-28·8) in the evorpacept plus pembrolizumab cohort, and 32·7 months (27·0-32·7) in the evorpacept plus trastuzumab cohort. Two (7%) dose-limiting toxicities in the first cycle were reported in patients who received single-agent evorpacept; neutropenia with an associated infection in one patient with gastroesophageal junction cancer who received 3 mg/kg once per week, and thrombocytopenia with associated bleeding in one patient with pancreatic cancer who received 30 mg/kg once every other week. No maximum tolerated dose was reached; the maximum administered doses were 10 mg/kg once per week or 30 mg/kg once every other week. The 10 mg/kg once per week dose was used in the expansion cohorts in combination with pembrolizumab or trastuzumab. The most common grade 3 or worse treatment-related adverse events were thrombocytopenia with single-agent evorpacept (two [7%] patients) and evorpacept plus pembrolizumab (two [4%]), and thrombocytopenia (two [7%]) and neutropenia (two [7%]) with evorpacept plus trastuzumab. In patients who received single-agent evorpacept, four treatment-related serious adverse events were reported. Five serious treatment-related adverse events related to evorpacept plus pembrolizumab were reported, and one serious adverse event related to evorpacept plus trastuzumab was reported. In response-evaluable patients in the dose-escalation phase (n=15) receiving single-agent evorpacept once per week, four (27%) had a best overall response of stable disease (two received 0·3 mg/kg, one received 3 mg/kg, and one received 10 mg/kg); in the 11 patients who received single-agent evorpacept at the highest dose of 30 mg/kg once every other week, two (18%) had stable disease. In the dose-expansion cohort, overall responses were recorded in four (20·0%; 95% CI 5·7-43·7) of 20 patients with HNSCC who received evorpacept plus pembrolizumab, in one (5·0%; 0·1-24·9) of 20 patients with NSCLC who received evorpacept plus pembrolizumab, and in four (21·1%; 6·1-45·6) of 19 patients with gastric or gastroesophageal junction cancer who received evorpacept plus trastuzumab.INTERPRETATIONThe safety findings support the use of evorpacept in combination with pembrolizumab or trastuzumab for patients with advanced solid tumours. Preliminary antitumour activity results support future investigation of evorpacept combined with pembrolizumab or trastuzumab in patients with HNSCC, gastric or gastroesophageal junction cancer, and NSCLC.FUNDINGALX Oncology.

159

项与 Evorpacept 相关的新闻（医药）

2025-05-02

·ir.alxoncology.com

ALX Oncology to Report First Quarter 2025 Financial Results on May 8, 2025

SOUTH SAN FRANCISCO, Calif., May 02, 2025 (GLOBE NEWSWIRE) -- ALX Oncology Holdings Inc., ("ALX Oncology" or the "Company") (Nasdaq: ALXO), a clinical-stage biotechnology company advancing a pipeline of novel therapies designed to treat cancer and extend patients’ lives, today announced plans to report its first quarter 2025 financial results on Thursday, May 8th, 2025, before market open. The company will not be hosting a teleconference in conjunction with its financial results press release. 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 and is anticipated to enter Phase 1 trials mid-2025. 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: Audra Friis, Sam Brown, Inc. audrafriis@sambrown.com (917) 519-9577

抗体药物偶联物财报临床1期

2025-04-28

·药明康德

使80%患者肿瘤细胞完全消失的组合疗法；使多种癌症类型患者疾病稳定的抗体疗法…… | 一周盘点

本期看点1. 下一代CD47阻断疗法evorpacept联用标准化疗方案治疗复发或难治性B细胞非霍奇金淋巴瘤（R/R B-NHL）的早期临床试验结果亮眼，80%患者获得完全缓解（CR），两年总生存（OS）率为84%。2. T细胞激活剂invikafusp alfa的1/2期临床试验结果积极，在肿瘤突变负荷高（TMB-H），对PD-1/PD-L1耐药且接受过大量前期治疗的难治性患者中的疾病控制率（DCR）为67%。3. Dectin-2靶向抗体BDC-3042在1期临床试验中展现积极抗肿瘤作用，在17例患有6种不同类型肿瘤的患者中，80%（12/15）的可评估患者达到了疾病稳定（SD）或更好的状态。Evorpacept（ALX148）：公布1/2期联合治疗试验数据ALX Oncology公司公布了其CD47抑制剂evorpacept与标准治疗方案利妥昔单抗和来那度胺（R²）联用的1/2期由研究者发起的临床试验（IST）的积极数据，该试验针对复发或难治性B细胞非霍奇金淋巴瘤患者。Evorpacept是一种下一代CD47阻断疗法，它将高亲和性CD47结合结构域与经特殊处理的Fc结构域相结合，因此无法激活Fc受体，有望降低CD47靶向抗体因激活Fc受体可能产生的毒副作用。此外，与其它抗CD47抗体相比，evorpacept的分子量更小，更容易渗透到实体瘤中，从而提高疗效。此次试验共纳入20例惰性（18例）和侵袭性（2例）R/R B-NHL患者，所有患者均曾接受过抗CD20单抗治疗。在中位随访28个月后，联合治疗组患者的两年无进展生存（PFS）率为69%，两年OS率为84%。16例患者（80%）达到CR，最佳总缓解率（ORR）为90%。18例接受evorpacept联用R²方案的惰性NHL患者的CR率为83%，高于历史上在仅使用R²方案的类似患者中观察到的34%的CR率。此外，治疗期间观察到T细胞和抗肿瘤巨噬细胞显著增加。安全性方面，该联合治疗方案耐受性良好，未出现剂量限制性毒性。Invikafusp alfa（STAR0602）：公布1/2期临床试验数据Marengo Therapeutics公司将公布其潜在“first-in-class”T细胞激活剂invikafusp alfa的1/2期临床试验更新结果。Invikafusp alfa是一款双特异性融合蛋白，它不但可以与T细胞受体的Vβ链结合，还可以激活另一条T细胞共刺激信号通路，促进特定效应Vβ T细胞的扩增，从而增强抗肿瘤免疫反应。摘要结果显示，在肿瘤突变负荷高（TMB-H），对PD-1/PD-L1耐药且接受过大量前期治疗的难治性患者中，优化剂量的invikafusp alfa在9名可评估疗效的患者中达到67%的DCR，其中两名患者获得确认部分缓解（PR），一名患者缓解持续时间超过12个月。此外，研究发现CD8阳性、Vβ T细胞的剂量依赖性、选择性扩增，在2期临床推荐剂量下最高扩增600%。扩增的Vβ T细胞表现出记忆表型并表达细胞毒性效应分子。基于初步临床及临床前结果，美国FDA已授予invikafusp alfa治疗TMB-H结直肠癌的快速通道资格。BDC-3042：公布1期临床试验数据Bolt Biotherapeutics公司公布了其抗体疗法BDC-3042的1期剂量递增研究结果。BDC-3042是一种靶向dectin-2的激动剂抗体，dectin-2是一种由肿瘤相关巨噬细胞（TAM）表达的免疫激活受体。作为C型凝集素受体，dectin-2在病原体识别及诱导保护性免疫反应中发挥着关键作用。截至2025年4月7日的数据，BDC-3042在10 mg/kg每两周一次的剂量下表现出良好的耐受性，未出现剂量限制性毒性或药物相关严重不良事件。同时，该药物显示出明确的生物学活性，促炎细胞因子和趋化因子水平呈剂量依赖性升高。BDC-3042展现出潜在的抗肿瘤活性，80%的可评估患者（12/15）的最佳缓解为SD或更好，所有3例非小细胞肺癌患者均实现≥12周的SD，包括1例未确认的PR。Tovecimig（CTX-009）：研究者发起的临床试验完成首例患者给药Compass Therapeutics公司宣布，其靶向DLL4和VEGF-A的双特异性抗体tovecimig（CTX-009）用于一线治疗胆道癌（BTC）的IST研究已完成首例患者给药。Tovecimig通过同时阻断促血管生成的DLL4和VEGF-A信号通路发挥抗肿瘤作用。临床前及早期临床数据显示，其在结直肠癌、胃癌、胆管癌、胰腺癌和非小细胞肺癌等多种实体瘤中具有活性。在既往接受过多种治疗且对已获批抗VEGF疗法产生耐药的晚期癌症患者群体中，已观察到接受tovecimig单药治疗的患者获得了PR。VS-7375：IND申请获得FDA许可Verastem Oncology公司宣布，美国FDA已批准其口服KRAS G12D（ON/OFF）抑制剂VS-7375的IND申请，公司预计将于2025年年中启动一项1/2a期临床研究，并计划在晚期实体瘤（如胰腺癌、结直肠癌和非小细胞肺癌）中开展多个扩展队列试验，包括联合疗法评估。VS-7375由Verastem Oncology与劲方医药合作开发，是一款口服高活性、高选择性小分子KRAS G12D（ON/OFF）抑制剂，通过非共价形式结合KRAS G12D蛋白，抑制其与下游效应蛋白结合，从而在细胞中破坏KRAS G12D对下游通路的持续活化，最终高效抑制肿瘤细胞增殖。参考资料（可上下滑动查看）[1] Korea’s InThera receives IND approval for norovirus vaccine candidate. Retrieved April 25, 2025, from https://www.koreabiomed.com/news/articleView.html?idxno=27327[2] Compass Therapeutics Announces First Patient Dosed in an Investigator Sponsored Trial of Tovecimig in the First-Line Setting for Patients with Biliary Tract Cancer. Retrieved April 25, 2025, from https://www.globenewswire.com/news-release/2025/04/21/3064600/0/en/Compass-Therapeutics-Announces-First-Patient-Dosed-in-an-Investigator-Sponsored-Trial-of-Tovecimig-in-the-First-Line-Setting-for-Patients-with-Biliary-Tract-Cancer.html[3] Aclaris Therapeutics Secures U.S. Food and Drug Administration IND Clearance for ATI-052, Enabling Advancement of its Novel Bispecific Anti-TSLP/IL-4R Investigational Antibody. Retrieved April 25, 2025, from https://www.globenewswire.com/news-release/2025/04/22/3065328/37216/en/Aclaris-Therapeutics-Secures-U-S-Food-and-Drug-Administration-IND-Clearance-for-ATI-052-Enabling-Advancement-of-its-Novel-Bispecific-Anti-TSLP-IL-4R-Investigational-Antibody.html[4] Tagworks Pharmaceuticals Announces FDA Clearance of IND Application and Initiation of Phase 1 Clinical Trial for TGW101 and Appoints Keith Orford, MD, PhD, as Chief Medical Officer. Retrieved April 25, 2025, from https://www.prnewswire.com/news-releases/tagworks-pharmaceuticals-announces-fda-clearance-of-ind-application-and-initiation-of-phase-1-clinical-trial-for-tgw101-and-appoints-keith-orford-md-phd-as-chief-medical-officer-302433654.html[5] Ensem Therapeutics Announces U.S. FDA IND Clearance to Initiate Clinical Development of ETX-636. Retrieved April 25, 2025, from https://www.businesswire.com/news/home/20250422440145/en/Ensem-Therapeutics-Announces-U.S.-FDA-IND-Clearance-to-Initiate-Clinical-Development-of-ETX-636[6] AP Biosciences Doses First Patient in Phase 1/2 Clinical Trials of AP402 for HER2+ Cancer Patients. Retrieved April 25, 2025, from https://www.globenewswire.com/news-release/2025/04/22/3065502/0/en/AP-Biosciences-Doses-First-Patient-in-Phase-1-2-Clinical-Trials-of-AP402-for-HER2-Cancer-Patients.html[7] Kymera Therapeutics Announces First Patient Dosed in BROADEN Phase 1b Atopic Dermatitis Clinical Trial of KT-621, a First-in-Class Oral STAT6 Degrader. Retrieved April 25, 2025, from https://www.globenewswire.com/news-release/2025/04/22/3065332/0/en/Kymera-Therapeutics-Announces-First-Patient-Dosed-in-BROADEN-Phase-1b-Atopic-Dermatitis-Clinical-Trial-of-KT-621-a-First-in-Class-Oral-STAT6-Degrader.html[8] Onward Therapeutics Announces IMPD Approval for Its Subsidiary Emercell to Start Clinical Investigation of Allogeneic NK Cell Therapy OT-C001 in Combination with Rituximab. Retrieved April 25, 2025, from https://www.prnewswire.com/news-releases/onward-therapeutics-announces-impd-approval-for-its-subsidiary-emercell-to-start-clinical-investigation-of-allogeneic-nk-cell-therapy-ot-c001-in-combination-with-rituximab-302433928.html[9] CytoAgents Announces Completion of Cohort 1 Dose-escalation Stage of Clinical Phase 1B to Advance Research on Cytokine Release Syndrome. Retrieved April 25, 2025, from https://www.businesswire.com/news/home/20250424559289/en/CytoAgents-Announces-Completion-of-Cohort-1-Dose-escalation-Stage-of-Clinical-Phase-1B-to-Advance-Research-on-Cytokine-Release-Syndrome[10] Verastem Oncology Announces U.S. IND Clearance of VS-7375, Oral KRAS G12D (ON/OFF) Inhibitor, Enabling Phase 1/2a Trial in Advanced Solid Tumors. Retrieved April 25, 2025, from https://pipelinereview.com/verastem-oncology-announces-u-s-ind-clearance-of-vs-7375-oral-kras-g12d-on-off-inhibitor-enabling-phase-1-2a-trial-in-advanced-solid-tumors/[11] Ascletis Announces Positive Topline Results of U.S. Phase Ib Multiple Ascending Dose Study of Small Molecule Oral GLP-1R Agonist ASC30 and Submission of 13-week Phase IIa Study Protocol to FDA. Retrieved April 25, 2025, from https://www.prnewswire.com/news-releases/ascletis-announces-positive-topline-results-of-us-phase-ib-multiple-ascending-dose-study-of-small-molecule-oral-glp-1r-agonist-asc30-and-submission-of-13-week-phase-iia-study-protocol-to-fda-302434655.html[12] Marengo to Share Updated Clinical Results from STARt-001 Phase 1/2 Clinical Trial Featuring Invikafusp Alfa Monotherapy Activity in PD1 Resistant Tumors at Upcoming AACR 2025 Clinical Plenary Oral Presentation. Retrieved April 25, 2025, from https://www.prnewswire.com/news-releases/marengo-to-share-updated-clinical-results-from-start-001-phase-12-clinical-trial-featuring-invikafusp-alfa-monotherapy-activity-in-pd1-resistant-tumors-at-upcoming-aacr-2025-clinical-plenary-oral-presentation-302437765.html[13] CT206 - ICAM-1 directed chimeric antigen receptor (CAR) T cells (AIC100) in patients with advanced thyroid cancers: Clinical and translational data from the phase 1 dose escalation study. Retrieved April 25, 2025, from https://www.abstractsonline.com/pp8/#!/20273/presentation/10430[14] Bolt Biotherapeutics Presents Results from the Phase 1 Dose-Escalation Clinical Study of BDC-3042 at AACR Annual Meeting 2025. Retrieved April 25, 2025, from https://www.globenewswire.com/news-release/2025/04/25/3068520/0/en/Bolt-Biotherapeutics-Presents-Results-from-the-Phase-1-Dose-Escalation-Clinical-Study-of-BDC-3042-at-AACR-Annual-Meeting-2025.html免责声明：本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新2

临床结果基因疗法临床1期细胞疗法

2025-04-27

·PipelineReview

ALX Oncology Reports ASPEN-03 and ASPEN-04 Phase 2 Trials Evaluating Evorpacept with a Checkpoint Inhibitor for the Treatment of Head and Neck Cancers Did Not Meet Primary Endpoints

SOUTH SAN FRANCISCO, CA, USA I April 25, 2025 I ALX Oncology Holdings Inc., (“ALX Oncology” or the “Company”) (Nasdaq: ALXO), a clinical-stage biotechnology company advancing a pipeline of novel therapies designed to treat cancer and extend patients’ lives, today announced topline data from its Phase 2 ASPEN-03 and ASPEN-04 clinical trials. The company’s investigational CD47-blocker evorpacept, when added to Merck’s (known as MSD outside of the US and Canada) anti-PD-1 therapy, KEYTRUDA ® (pembrolizumab) with or without chemotherapy, did not meet the primary endpoints in the ASPEN-03 and ASPEN-04 trials of improved objective response rates (ORR) as compared to historical controls of pembrolizumab alone and pembrolizumab with chemotherapy, respectively, as a first-line treatment in patients with advanced head and neck squamous cell carcinoma (HNSCC). The combination of evorpacept and pembrolizumab with or without chemotherapy in ASPEN-03 and ASPEN-04 demonstrated a manageable safety profile and was consistent with what has been previously reported for pembrolizumab and chemotherapy in this setting. Although the company will no longer pursue evorpacept in combination with pembrolizumab in HNSCC, multiple clinical trials of evorpacept in combination with anti-cancer antibodies will continue based on established proof-of-concept. Evorpacept blocks the ‘don’t eat me’ signal transmitted by CD47 on the surface of cancer cells that these cells use to evade detection by the immune system. As its primary mechanism of action, evorpacept is uniquely designed to stimulate macrophages to selectively attack cancer cells and not healthy cells, when combined with active anti-cancer antibodies. This mechanism has translated into durable clinical responses and a well-tolerated safety profile in HER2-positive gastric and HER2-positive breast cancer clinical trials. To further explore the benefit in this setting, evorpacept is currently being evaluated in combination with various anti-cancer antibodies in colorectal cancer, breast cancer, non-Hodgkin lymphoma and multiple myeloma. In the ASPEN-03 and ASPEN-04 clinical trials, evorpacept was combined with pembrolizumab with or without chemotherapy to investigate a second and distinct mechanism of action. This discrete approach explored the concept that evorpacept may enhance T-cell priming by activating dendritic cells and stimulating the adaptive immune system. The trial outcomes were not sufficiently supportive of advancing evorpacept in combination with pembrolizumab in HNSCC into a registrational trial. “While there were encouraging trends in ASPEN-03 in ORR versus the historical and internal control, we’ve decided not to pursue evorpacept and pembrolizumab in head and neck cancer in light of our prioritization of the more established anti-cancer antibody combination program based on multiple positive studies,” said Alan Sandler, M.D., Chief Medical Officer at ALX Oncology. “We are disappointed that these studies did not meet their primary endpoints, most importantly for the patients for whom current standard-of-care treatment approaches fall short, and we thank all who participated in the trials.” “Moving forward, we are continuing to rapidly advance our clinical program combining evorpacept with anti-cancer antibodies supported by robust clinical data across trials in multiple tumor types. Evorpacept has demonstrated response rates and durability beyond what is expected from standard of care across several studies when combined with HERCEPTIN ® , zanidatamab and RITUXAN ® ,” said Jason Lettmann, Chief Executive Officer at ALX Oncology. “Based on the positive data and strong mechanistic rationale, we maintain our confidence in the evorpacept clinical development program and intend to deliver on that promise with additional clinical data in breast cancer and colorectal cancer in the near-term. With evorpacept and ALX2004, our novel EGFR-targeted antibody-drug conjugate, we continue our commitment to bringing forth meaningful therapies for patients living with cancer.” Detailed findings from the ASPEN-03 and ASPEN-04 trials will be submitted to a future medical meeting. KEYTRUDA ® is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. About ASPEN-03 and ASPEN-04 Clinical Trials ASPEN-03 and ASPEN-04 are randomized, multi-center, international Phase 2 trials evaluating evorpacept, ALX Oncology’s investigational CD47-blocking therapeutic that uniquely combines a high-affinity CD47-binding domain with an inactivated proprietary Fc domain, in patients with metastatic or unresectable, recurrent HNSCC who have not yet been treated for their advanced disease. The ASPEN-03 trial ( NCT04675294 ) is evaluating evorpacept in combination with Merck’s anti-PD-1 therapy, KEYTRUDA ® (pembrolizumab) against pembrolizumab alone for the treatment of patients whose HNSCC is PD-L1 positive. The ASPEN-04 trial ( NCT04675333 ) is evaluating evorpacept in combination with pembrolizumab and chemotherapy against pembrolizumab and chemotherapy alone in patients with HNSCC, regardless of PD-L1 status. Patient characteristics in the trials (N=346) were generally well-balanced across arms. The primary endpoints for the ASPEN-03 and ASPEN-04 trials is ORR compared to historical control. Key secondary endpoints for both trials are safety, duration of response (DOR), progression-free survival (PFS) and overall survival (OS). About Head and Neck Squamous Cell Carcinoma (HNSCC) HNSCC is a serious and life-threatening disease that originates in the squamous cells lining the mucosal surfaces of the head and neck, including the mouth, throat, voice box, sinuses and nasal cavity. HNSCC is the seventh most common cancer worldwide and the incidence of HNSCC is expected to increase 30% by 2030. Despite current standard-of-care therapies and recent advancements in diagnosis and treatment, people with HNSCC face a poor prognosis, particularly when diagnosed at advanced stages. Further, the survival rate for HNSCC has only modestly improved in recent years, even with the availability of new treatment modalities, underscoring a need for improved therapeutics. About Evorpacept ALX Oncology’s lead therapeutic candidate, evorpacept, is a highly differentiated potential best- and first-in-class CD47 checkpoint inhibitor and one of the most advanced checkpoint inhibitors to target and activate the innate immune system. Evorpacept was intentionally designed to maximize the clinical potential of blocking CD47, while reducing the toxicities associated with previous approaches to CD47 blockade. In clinical studies across a wide spectrum of tumor types in more than 700 patients to date, evorpacept has demonstrated potential to enhance the therapeutic activity of many of the most important cancer therapies available today, contributing an additional, differentiated immuno-oncology mechanism. Based on this potential, ALX Oncology is advancing a robust clinical program evaluating evorpacept in a wide range of cancer indications, prioritizing its combination with anti-cancer antibodies in breast, gastric and colon cancers. The U.S. Food and Drug Administration (FDA) has granted Fast Track designation to evorpacept for the second-line treatment of patients with HER2-positive gastric or GEJ carcinoma. Additionally, both the FDA and European Commission have granted Orphan Drug Designation for this indication. 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 and is anticipated to enter Phase 1 trials mid-2025. More information is available at www.alxoncology.com and on LinkedIn @ALX Oncology . SOURCE: ALX Oncology

临床2期孤儿药免疫疗法临床结果快速通道

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
转移性胃腺癌	临床3期	法国	Eli Lilly & Co.	2022-01-15
转移性胃腺癌	临床3期	捷克	Eli Lilly & Co.	2022-01-15
转移性胃腺癌	临床3期	新加坡	Eli Lilly & Co.	2022-01-15
转移性胃腺癌	临床3期	意大利	ALX Oncology, Inc.	2022-01-15
转移性胃腺癌	临床3期	英国	ALX Oncology, Inc.	2022-01-15
转移性胃腺癌	临床3期	日本	ALX Oncology, Inc.	2022-01-15
转移性胃腺癌	临床3期	法国	ALX Oncology, Inc.	2022-01-15
转移性胃腺癌	临床3期	英国	Eli Lilly & Co.	2022-01-15
转移性胃腺癌	临床3期	比利时	Eli Lilly & Co.	2022-01-15
转移性胃腺癌	临床3期	西班牙	ALX Oncology, Inc.	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 (AACR2025) 人工标引	临床1期	非霍奇金淋巴瘤	20	Evorpacept + lenalidomide + rituximab	(艱觸簾鏇淵衊鹽壓廠鬱) = 繭壓製餘積夢艱範鑰積蓋觸顧蓋夢鹽簾鏇醖蓋 (膚築齋積壓齋網遞範鹽 ) 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	-	Evorpacept + pembrolizumab	(網蓋夢構艱構鹽簾繭顧) = Not Meet Primary Endpoints 齋積願糧鏇構願憲顧壓 (構獵鹽鬱構鏇構鑰夢構 ) 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	(簾選餘鹹鏇鏇糧鑰膚衊) = Not Meet Primary Endpoints. 廠廠築構築壓觸廠醖膚 (鑰艱醖淵艱齋鏇鏇選糧 ) 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)	(蓋鹽壓鬱簾廠廠膚鑰網) = 網願製構繭鏇鑰範積鹹憲獵遞鏇獵襯淵獵繭鹽 (壓齋壓遞壓鹹鹽蓋憲淵 ) 更多	积极	2025-01-23
				Trastuzumab (T) + Ramucirumab (R) + Paclitaxel (P)	(蓋鹽壓鬱簾廠廠膚鑰網) = 衊淵淵築淵膚繭範簾醖憲獵遞鏇獵襯淵獵繭鹽 (壓齋壓遞壓鹹鹽蓋憲淵 ) 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	127	Evorpacept + Trastuzumab + Ramucirumab + Paclitaxel	(夢憲夢餘遞醖構獵築網) = 製獵觸鹹積窪鏇觸糧鑰遞遞鑰膚衊鏇淵鹹鏇夢 (鹹糧築製糧蓋簾願艱襯, 29.0 ~ 54.4) 更多	积极	2025-01-23
				Trastuzumab + Ramucirumab + Paclitaxel	(夢憲夢餘遞醖構獵築網) = 襯齋壓夢齋窪鑰範鹽艱遞遞鑰膚衊鏇淵鹹鏇夢 (鹹糧築製糧蓋簾願艱襯, 16.3 ~ 39.1) 更多
NCT05002127 (ASPEN-06, Company_Website) 人工标引	临床2/3期	HER2阳性胃癌 \| HER2阳性胃食管结合部腺癌	127	Evorpacept + trastuzumab + CYRAMZA + paclitaxel	(築壓製鹽夢簾鹽淵選構) = 鑰齋觸鹽鏇繭鹹構顧簾築鬱醖製簾構鏇觸選憲 (鬱艱鹹願鏇鏇膚積觸製 ) 更多	积极	2024-07-31
				Trastuzumab + CYRAMZA + paclitaxel	(築壓製鹽夢簾鹽淵選構) = 醖鹹鹹憲觸廠製鹽夢觸築鬱醖製簾構鏇觸選憲 (鬱艱鹹願鏇鏇膚積觸製 ) 更多
NCT05524545 (ASCO2024) 人工标引	临床1期	局部晚期尿路上皮癌 \| 转移性尿路上皮癌	20	Evorpacept 20 mg/kgenfortumab vedotin	(顧網鬱構積願簾膚範鹽) = Not observed. 窪淵鑰鑰製構餘築獵艱 (齋製積醖範壓夢選淵艱 ) 更多	积极	2024-05-24
NCT05167409 (ASCO2024) 人工标引	临床2期	转移性微卫星稳定结直肠癌	16	Evorpacept (E) 15 mg/kgcetuximabpembrolizumab	(獵顧鹽齋製蓋憲鹽蓋鏇) = 遞獵觸構獵廠簾夢範範鏇獵範襯觸顧襯遞獵餘 (觸選鑰糧憲窪繭淵夢構 ) 更多	不佳	2024-05-24
NCT05025800 (AACR2024) 人工标引	临床1期	非霍奇金淋巴瘤	20	Evorpacept+rituximab+lenalidomide	願淵願鬱糧積鏇積夢齋(鬱觸網繭廠憲網鏇選淵) = 壓築艱窪鹽壓簾鹽簾艱鏇鑰窪窪憲襯艱艱夢醖 (鬱繭願範膚鑰鹽膚衊糧 ) 更多	积极	2024-04-05
NCT05002127 (ASPEN-06, NEWS) 人工标引	临床2期	转移性 HER2 阳性胃食管结合部癌 \| HER2阳性胃癌二线 HER2 Positive	54	Evorpacept 30 mg/kg+trastuzumab + CYRAMZA + paclitaxel	(製願艱鹽鏇簾簾網鏇製) = 憲簾獵餘醖鹽淵選鬱鹽廠壓鹹齋遞簾獵鑰觸積 (膚艱壓範繭艱鏇觸夢觸 ) 更多	积极	2023-10-03
				trastuzumab + CYRAMZA + paclitaxel	(製願艱鹽鏇簾簾網鏇製) = 鑰餘製餘壓鹹顧淵網餘廠壓鹹齋遞簾獵鑰觸積 (膚艱壓範繭艱鏇觸夢觸 ) 更多