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2022-12-22

申办/合作机构

Quantumleap Healthcare Collaborative

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2022-12-16

申办/合作机构

ALX Oncology, Inc.

[+1]

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）

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

BACKGROUND:

Both 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.

METHODS:

We 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.

FINDINGS:

Between 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.

INTERPRETATION:

The 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.

FUNDING:

ALX Oncology.

2020-10-01·Transfusion3区 · 医学

Assessing and mitigating the interference of ALX148, a novel CD47 blocking agent, in pretransfusion compatibility testing

3区 · 医学

Article

作者: Hustinx, Hein ; Yoon, Mi Sook ; Kim, Hyungsuk ; Kim, Tae Yeul ; Wan, Hong I. ; Sim, Janet

Background:

ALX148, a novel CD47 blocking agent, is in clinical development for the treatment of advanced solid tumors and lymphoma. Because CD47 is highly expressed on red blood cells (RBCs), its therapeutic blockade can potentially interfere with pretransfusion compatibility testing. This study describes the interference of ALX148 in pretransfusion compatibility testing and evaluates the methods used for mitigating such interference.

Study Design and Methods:

Routine serologic tests were performed on six samples from four patients treated with ALX148. Antibody screening tests were performed on ALX148‐spiked plasma, and RBC testing including antigen typing was performed on ALX148‐coated RBCs. Soluble CD47 or high‐affinity signal regulatory protein α (SIRPα) monomers were used to remove the false‐positive reactivity of ALX148‐spiked plasma with or without anti‐E.

Results:

ALX148 caused false‐positive reactivity in antibody screening using indirect antiglobulin testing (IAT) and two‐stage papain testing. However, false‐positive reactivity was not observed at the immediate spin (IS), room temperature (RT), and 37°C phases. Direct antiglobulin testing, autologous controls, and eluates showed positive results. ALX148 did not affect blood group antigen typing performed at the IS or RT phases. The use of 50‐ to 100‐fold molar excess of soluble CD47 or 300‐fold molar excess of high‐affinity SIRPα monomers removed false‐positive reactivity in IAT without affecting anti‐E detection.

Conclusion:

ALX148 generates false‐positive reactivity in IAT, interfering with pretransfusion compatibility testing. The use of soluble CD47 or high‐affinity SIRPα monomers can resolve the interference without possibly missing clinically significant alloantibodies.

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.

117

项与 Evorpacept 相关的新闻（医药）

2024-06-09

·药明康德

疾病控制率达100%的免疫联合疗法；使月度发作率下降98%的基因编辑疗法…… | 一周盘点

▎药明康德内容团队编辑本期看点 1. 新型口服双重抑制剂TU2218联用PD-1抑制剂pembrolizumab治疗晚期实体瘤患者，在一项1b期临床试验中的疾病控制率（DCR）达100%。 2. 用于治疗遗传性血管水肿（HAE）的在研体内CRISPR基因编辑疗法NTLA-2002早期临床数据亮眼，单次给药后使患者的月度发作率平均下降了98%。 3. 现货型基因疗法PRGN-2012治疗复发性呼吸乳头状瘤病（RRP）患者的1/2期临床试验达到主要终点，有望成为首个获得FDA批准的用于治疗RRP的疗法。 4. 男性无激素避孕药YCT-529完成了1a期临床试验，在临床前研究中，该候选疗法预防小鼠妊娠的有效率为99%，且100%可逆。药明康德内容团队整理 TU2218：公布1b期临床试验的中期数据 TiumBio公司公布了新型口服双重抑制剂TU2218联用PD-1抑制剂pembrolizumab治疗晚期实体瘤患者1b期临床试验的中期结果。TU2218靶向转化生长因子β受体1（TGFR1）和血管内皮生长因子受体2（VEGFR2）。肿瘤微环境中的TGF-ß和VEGF通路会干扰免疫检查点抑制剂的抗肿瘤活性，因此TU2218有望通过抑制这两种通路最大限度地提高免疫疗法的疗效。此次公布的结果显示，5名接受2期推荐剂量（RP2D）TU2218联用pembrolizumab治疗的患者的DCR为100%，其中两名患者达到了部分缓解（PR），3名患者达到了疾病稳定（SD）。所有剂量组中，12名接受联合治疗的患者中有2人达到了PR，6人达到了SD。在这项研究中，TU2218联用pembrolizumab的耐受性良好，没有观察到剂量限制性毒性（DLT），这与之前的单药治疗试验一致。 NTLA-2002：公布1期临床试验的长期数据 Intellia Therapeutics公司宣布其用于治疗遗传性血管水肿的在研疗法NTLA-2002的1期临床试验的长期数据。NTLA-2002是一种体内CRISPR基因编辑候选疗法，通过脂质纳米颗粒（LNP）以mRNA形式递送CRISPR-Cas9基因编辑系统，靶向敲除血浆前激肽释放酶（KLKB1）基因，以永久性降低血浆中激肽释放酶活性，从而防止遗传性血管水肿的发作。此次公布的结果显示，中位随访时间为20.1个月时，单次NTLA-2002治疗让患者的月均疾病发作率平均减少了98%，中度至重度发作平均减少了99%。在测试的每个剂量水平上，HAE发作率均显著减少。单次输注后，患者最长的无发作期超过26个月，并且仍在持续。此外，100%接受NTLA-2002治疗的患者在停止其他预防性治疗后无需再进行预防性治疗。 PRGN-2012：公布1/2期临床试验的新数据 Precigen公司公布了其现货型基因疗法PRGN-2012治疗复发性呼吸乳头状瘤病患者的1/2期临床试验数据。PRGN-2012旨在激发对抗受HPV6或HPV11感染细胞的免疫反应，以治疗RRP。此前，PRGN-2012已获得FDA和欧盟委员会授予的孤儿药资格，还获得了FDA授予的突破性疗法认定。此次公布的结果显示，该1/2期临床试验达到了主要的安全性和疗效终点。中位随访时间为20个月时，51%（18/35）接受PRGN-2012治疗的患者达到了完全缓解（CR），且不再需要进行手术治疗，CR持续时间超过12个月。86%的患者在接受PRGN-2012治疗后的一年内需要进行的手术次数较治疗前一年减少，从治疗前一年的中位次数4次减少到接受治疗后的0次。此外，PRGN-2012显著改善了达到CR患者的Derkay评分（一种用于测量RRP生长程度的量表）和生活质量评分。安全性方面，PRGN-2012的耐受性良好，无DLT，也没有＞2级的治疗相关不良事件。 ▲PRGN-2012的1/2期临床试验结果（图片来源：参考资料[9]）该公司计划在2024年下半年通过加速批准途径提交PRGN-2012的滚动生物制品许可申请（BLA）。新闻稿指出，如果获得批准，PRGN-2012有可能成为首个获得FDA批准用于治疗RRP的疗法。 YCT-529：公布1a期临床试验数据 YourChoice Therapeutics公司公布其男性无激素避孕药YCT-529的1a期临床试验结果。YCT-529是一种视黄酸受体-α（RAR-a）抑制剂，通过阻断RAR-α来阻止睾丸中精子的产生和释放。临床前研究表明，YCT-529在预防小鼠妊娠方面有99%的有效性，且100%可逆。该研究的结果表明，YCT-529是安全的。 C-CAR031：公布1期临床试验的初步数据阿斯利康（AstraZeneca）公布其GPC3靶向CAR-T疗法C-CAR031的最新临床试验结果。GPC3是一种在肝癌中过表达的表面抗原，该蛋白在健康组织中几乎不存在。C-CAR031是一种GPC3靶向的自体CAR-T疗法，这款CAR-T疗法还同时“装备”了TGFβ以抵抗免疫抑制微环境，以增强其效力。此次公布的结果显示，中位随访时间为5.82个月时，22例可评估疗效的GPC3阳性晚期肝细胞癌（HCC）患者的DCR为90.9%，客观缓解率为50.0%，且该疗法的安全性可控。阿斯利康的早期肿瘤学开发负责人Matt Hellmann博士在接受行业媒体STAT采访时表示：“这是首个在肝癌治疗上显示具疗效的CAR-T疗法。这也是GPC3靶点的首次临床验证。” ▲C-CAR031的疗效结果摘要（图片来源：参考资料[1]） CB-010：公布1期临床试验数据 Caribou Biosciences公司公布了其同种异体CAR-T细胞疗法CB-010治疗复发/难治性B细胞非霍奇金淋巴瘤患者的新数据。CB-010利用基因编辑技术生成，除了表达靶向CD19的嵌合抗原受体，还利用基因编辑技术敲除了免疫检查点蛋白PD-1的表达，旨在提高抗肿瘤活性的持久性。截至2024年4月1日的数据，CB-010的疗效和安全性可与已获批的自体CAR-T细胞疗法相媲美。13名部分人类白细胞抗原（HLA）匹配（≥4个等位基因）患者的总缓解率达92%，CR率为46%，中位无进展生存期（PFS）获得改善，为14.4个月。 ▲接受CB-010治疗患者的无进展生存曲线（图片来源：参考资料[4]） ▲接受CB-010治疗患者的疗效结果（图片来源：参考资料[4]） INB-200：公布1期临床试验的新数据 IN8bio公司公布其耐化疗的转基因自体γδ T细胞疗法INB-200用于治疗新确诊的多形性胶质母细胞瘤的积极早期数据。INB-200是一种强大的协同治疗方法，能在患者接受化疗时持续存在，并保持其识别、参与和杀死癌细胞的自然能力。截至2024年5月30日的数据，中位随访时间为11.7个月，92%接受INB-200治疗的可评估患者的中位PFS超过了7个月（即接受标准治疗方案的患者的中位PFS）。一名患有IDH突变神经胶质瘤的患者在接受治疗后的34.9+个月时仍然存活，且疾病没有进展。近期发表的一项IDH抑制剂治疗IDH突变脑胶质瘤患者的临床试验中，对照组患者的中位PFS为11.1个月，试验组患者的中位PFS为28.5个月。安全性方面，在任何队列中均未报告与治疗相关的严重不良事件、DLT、细胞因子释放综合征、输注反应或免疫效应细胞相关神经毒性综合征。 IFx-2.0：公布1b期临床试验数据 TuHURA Biosciences公司公布了其个体化的候选癌症疫苗IFx-2.0治疗对免疫检查点抑制剂（ICI）耐药的晚期Merkel细胞癌（MCC）和皮肤鳞状细胞癌（cSCC）患者的1b期试验的初步结果。该候选疗法旨在克服患者对ICI的原发性耐药。此次公布的结果显示，连续三周每周给药一次IFx-2.0的耐受性良好。5名此前接受ICI治疗后在3.8个月内疾病就发生进展的晚期MCC患者中，有4人在接受IFx-2.0治疗后重新对ICI治疗产生了持久的应答，包括1例CR、1例病理完全缓解（pCR）和两例PR。患者的平均缓解时间为25个月，其中两名患者已分别持续缓解19个月和23个月，并且仍在持续缓解中。 MDNA11：公布1/2期临床试验的新数据 Medicenna Therapeutics公司公布了其下一代长效IL-2超级激动剂MDNA11治疗晚期实体瘤的新临床结果。MDNA11具有优秀的CD122（IL-2受体β）结合作用，而没有CD25（IL-2受体α）亲和力，从而能优先刺激癌症杀伤效应T细胞和NK细胞。此次公布的结果显示，MDNA11的耐受性良好，没有报告DLT和血管渗漏综合征。MDNA11在胰腺癌患者中表现出持久的缓解，1例转移性胰腺导管腺癌患者在基线时存在的所有病灶均完全消退，已维持超过104周，在停止治疗4个月后仍然保持着缓解。一例双检查点抑制剂治疗后进展的黑色素瘤患者的靶病灶在第28周时完全消退，在第44周的扫描时靶病灶仍保持完全消退。目前，该患者仍在接受MDNA11的治疗，非靶病灶也在继续消退。 WTX-124：公布1/1b期临床试验数据 Werewolf Therapeutics公司公布了其条件激活的白介素-2（IL-2）候选疗法WTX-124治疗接受过ICI治疗的局部晚期或转移性实体瘤患者的1/1b期临床试验数据。结果显示，WTX-124在此类患者中具有临床活性，且耐受性良好。截至2024年5月1日的数据，接受WTX-124单药治疗的患者中有1人获得了持久并经过确认的CR，2人达到了PR。获得缓解的患者在治疗的前两个治疗周期内就出现了缓解，并且靶病灶实现了100%的消退。此外，没有发现WTX-124联用pembrolizumab出现新的安全信号。 ▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放参考资料（可上下滑动查看） [1] Phase I study of C-CAR031, a GPC3-specific TGFβRIIDN armored autologous CAR-T, in patients with advanced hepatocellular carcinoma (HCC). Retrieved June 4, 2024 from https://meetings.asco.org/abstracts-presentations/234377 [2] Virion Therapeutics Reports Positive First-in-human, First-in-class, Phase 1b Immunogenicity Data of VRON-0200, a Novel Checkpoint Modifier for HBV Functional Cure at EASL Congress. Retrieved June 5, 2024, from https://www.prnewswire.com/news-releases/virion-therapeutics-reports-positive-first-in-human-first-in-class-phase-1b-immunogenicity-data-of-vron-0200-a-novel-checkpoint-modifier-for-hbv-functional-cure-at-easl-congress-302161948.html [3] TiumBio Presents Phase 1b Interim Results for TU2218 in Combination with Pembrolizumab at ASCO 2024 Annual Meeting. Retrieved June 7, 2024, from https://www.prnewswire.com/news-releases/tiumbio-presents-phase-1b-interim-results-for-tu2218-in-combination-with-pembrolizumab-at-asco-2024-annual-meeting-302160236.html [4] Caribou Biosciences Presents Encouraging Clinical Data from CB-010 ANTLER Phase 1 Trial in Second-line LBCL Patients at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting. Retrieved June 7, 2024, from https://www.globenewswire.com/news-release/2024/06/02/2891868/0/en/Caribou-Biosciences-Presents-Encouraging-Clinical-Data-from-CB-010-ANTLER-Phase-1-Trial-in-Second-line-LBCL-Patients-at-the-2024-American-Society-of-Clinical-Oncology-ASCO-Annual-M.html [5] Werewolf Therapeutics to Present Data from Ongoing Phase 1/1b Clinical Trial of WTX-124 as Monotherapy and in Combination with Pembrolizumab in Solid Tumors. Retrieved June 7, 2024, from https://investors.werewolftx.com/news-releases/news-release-details/werewolf-therapeutics-present-data-ongoing-phase-11b-clinical [6] Medicenna To Present Evidence of Durable Single Agent Activity and Potent Immune Effector Response with MDNA11 in the Dose Escalation Portion of Phase 1/2 ABILITY-1 Study at the 10th Annual Oncology Innovation Forum. Retrieved June 7, 2024, from https://ir.medicenna.com/news-releases/news-release-details/medicenna-present-evidence-durable-single-agent-activity-and [7] Intellia Therapeutics Announces Positive Long-Term Data from Ongoing Phase 1 Study of NTLA-2002, an Investigational In Vivo CRISPR Gene Editing Treatment for Hereditary Angioedema (HAE). Retrieved June 3, 2024, from https://ir.intelliatx.com/news-releases/news-release-details/intellia-therapeutics-announces-positive-long-term-data-ongoing [8] TuHURA Biosciences and Kintara Therapeutics Announce Positive Results from Phase 1b Trial of IFx-2.0, a Novel Personalized Cancer Vaccine, in Checkpoint Inhibitor Resistant Advanced Merkel Cell Carcinoma (MCC) and Cutaneous Squamous Cell Carcinoma (cSCC). Retrieved June 7, 2024, from https://www.prnewswire.com/news-releases/tuhura-biosciences-and-kintara-therapeutics-announce-positive-results-from-phase-1b-trial-of-ifx-2-0--a-novel-personalized-cancer-vaccine-in-checkpoint-inhibitor-resistant-advanced-merkel-cell-carcinoma-mcc-and-cutaneous-squamo-302161301.html [9] Precigen Announces Groundbreaking Pivotal Study Data for PRGN-2012 in Patients with Recurrent Respiratory Papillomatosis in Which More than Half of Patients Achieved Complete Response. Retrieved June 7, 2024, from https://www.prnewswire.com/news-releases/precigen-announces-groundbreaking-pivotal-study-data-for-prgn-2012-in-patients-with-recurrent-respiratory-papillomatosis-in-which-more-than-half-of-patients-achieved-complete-response-302161493.html [10] YourChoice Therapeutics Completes Phase 1a Clinical Study for First Hormone-Free Male Birth Control Pill. Retrieved June 7, 2024, from https://www.businesswire.com/news/home/20240603886060/en/ [11] IN8bio Presents Progression-Free Survival Update from Phase 1 Study of INB-200 at 2024 American Society of Clinical Oncology Annual Meeting. Retrieved June 7, 2024, from https://investors.in8bio.com/news-releases/news-release-details/in8bio-presents-progression-free-survival-update-phase-1-study [12] 4DMT Presents Positive Interim Data from Phase 1/2 AEROW Clinical Trial of Aerosolized 4D-710 for Modulator-Ineligible/-Intolerant Cystic Fibrosis at 47th European Cystic Fibrosis Conference. Retrieved June 7, 2024, from https://www.globenewswire.com/news-release/2024/06/06/2894575/0/en/4DMT-Presents-Positive-Interim-Data-from-Phase-1-2-AEROW-Clinical-Trial-of-Aerosolized-4D-710-for-Modulator-Ineligible-Intolerant-Cystic-Fibrosis-at-47th-European-Cystic-Fibrosis-C.html [13] Mythic Therapeutics Presents Initial Dose Escalation Data from Ongoing Phase 1 KisMET-01 Study on MYTX-011 at the American Society of Clinical Oncology (ASCO) Annual Meeting. Retrieved June 7, 2024, from https://www.businesswire.com/news/home/20240603700748/en [14] Syndax Announces Plans to Advance into Phase 1b Portion of Trial Evaluating Revumenib in Relapsed or Refractory Metastatic MSS CRC. Retrieved June 7, 2024, from https://www.prnewswire.com/news-releases/syndax-announces-plans-to-advance-into-phase-1b-portion-of-trial-evaluating-revumenib-in-relapsed-or-refractory-metastatic-mss-crc-302165405.html [15] BridgeBio Oncology Therapeutics announces first patient dosed with BBO-8520 in the Ph. 1 ONKORAS-101 trial for KRASG12C NSCLC. Retrieved June 7, 2024, from https://www.businesswire.com/news/home/20240606977682/en/ [16] Vivet Therapeutics Presents Interim Data from its Phase 1/2 GATEWAY Trial for the Treatment of Wilson Disease at EASL Congress 2024. Retrieved June 7, 2024, from https://www.prnewswire.com/news-releases/vivet-therapeutics-presents-interim-data-from-its-phase-12-gateway-trial-for-the-treatment-of-wilson-disease-at-easl-congress-2024-302164666.html [17] Altimmune Presents Data at EASL International Liver Congress™ 2024 Supporting the Disease Modifying Potential and Differentiated Therapeutic Profile of Pemvidutide in Metabolic Dysfunction-Associated Steatohepatitis (MASH). Retrieved June 7, 2024, from https://www.globenewswire.com/news-release/2024/6/5/2893731/0/en/Altimmune-Presents-Data-at-EASL-International-Liver-Congress-2024-Supporting-the-Disease-Modifying-Potential-and-Differentiated-Therapeutic-Profile-of-Pemvidutide-in-Metabolic-Dysf.html [18] Quell Therapeutics Advances QEL-001, its Multi-modular Engineered CAR-Treg Cell Therapy, into Efficacy Cohort of LIBERATE Phase 1/2 Trial in Liver Transplant Patients. Retrieved June 7, 2024, from https://www.globenewswire.com/news-release/2024/06/04/2893353/0/en/Quell-Therapeutics-Advances-QEL-001-its-Multi-modular-Engineered-CAR-Treg-Cell-Therapy-into-Efficacy-Cohort-of-LIBERATE-Phase-1-2-Trial-in-Liver-Transplant-Patients.html [19] Surrozen Initiates Dosing of First Patient in Phase 1b Clinical Trial of SZN-043 for Severe Alcohol-Associated Hepatitis. Retrieved June 7, 2024, from https://www.globenewswire.com/news-release/2024/06/04/2893050/0/en/Surrozen-Initiates-Dosing-of-First-Patient-in-Phase-1b-Clinical-Trial-of-SZN-043-for-Severe-Alcohol-Associated-Hepatitis.html [20] Cue Biopharma Presents Updated Data from Phase 1 Trial of CUE-101 in Recurrent/Metastatic HPV+ Head and Neck Cancer at the 2024 ASCO Annual Meeting. Retrieved June 7, 2024, from https://www.globenewswire.com/news-release/2024/06/04/2892974/0/en/Cue-Biopharma-Presents-Updated-Data-from-Phase-1-Trial-of-CUE-101-in-Recurrent-Metastatic-HPV-Head-and-Neck-Cancer-at-the-2024-ASCO-Annual-Meeting.html [21] Merus Presents Interim Data on MCLA-145 Monotherapy and in Combination with Pembrolizumab at the 2024 ASCO® Annual Meeting. Retrieved June 7, 2024, from https://ir.merus.nl/news-releases/news-release-details/merus-presents-interim-data-mcla-145-monotherapy-and-combination [22] BlueSphere Bio Announces IND Clearance of its First in Human Candidate and New Cell Therapy Portfolio for High-Risk Leukemia Patients. Retrieved June 7, 2024, from https://www.globenewswire.com/news-release/2024/06/03/2892552/0/en/BlueSphere-Bio-Announces-IND-Clearance-of-its-First-in-Human-Candidate-and-New-Cell-Therapy-Portfolio-for-High-Risk-Leukemia-Patients.html [23] Grey Wolf Therapeutics Presents First Clinical Data for GRWD5769, a First-in-Class ERAP1 Inhibitor, at the 2024 American Society for Clinical Oncology (ASCO) Annual Meeting. Retrieved June 7, 2024, from https://www.prnewswire.com/news-releases/grey-wolf-therapeutics-presents-first-clinical-data-for-grwd5769-a-first-in-class-erap1-inhibitor-at-the-2024-american-society-for-clinical-oncology-asco-annual-meeting-302161297.html [24] Puma Biotechnology Announces Presentation of Findings from a Phase I/Ib Study of Alisertib in Advanced EGFR-Mutated Lung Cancer. Retrieved June 7, 2024, from https://www.businesswire.com/news/home/20240603691086/en [25] Cyclacel Pharmaceuticals Reports New Clinical Data at 2024 ASCO Annual Meeting Highlighting Oral Fadraciclib’s Potential as a Precision Medicine for Cancer. Retrieved June 7, 2024, from https://investor.cyclacel.com/news-releases/news-release-details/cyclacel-pharmaceuticals-reports-new-clinical-data-2024-asco [26] Obsidian Therapeutics Announces Additional OBX-115 Safety and Efficacy Data in Oral Presentation at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting. Retrieved June 7, 2024, from https://www.businesswire.com/news/home/20240603008329/en [27] Replimune Presents RP1 Data from the IGNYTE anti-PD1 Failed Melanoma Cohort and RP2 Data in Uveal Melanoma at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting. Retrieved June 7, 2024, from https://ir.replimune.com/news-releases/news-release-details/replimune-presents-rp1-data-ignyte-anti-pd1-failed-melanoma [28] RS Oncology Announces Positive Data from a Phase 1 Clinical Trial of RSO-021, a First-in-Class Therapeutic for Malignant Pleural Mesothelioma. Retrieved June 7, 2024, from https://www.businesswire.com/news/home/20240603559175/en [29] Ascendis Pharma Presents New Data and Updated Results from Phase 1/2 IL-Believe Trial at ASCO 2024. Retrieved June 7, 2024, from https://www.globenewswire.com/news-release/2024/06/03/2892565/0/en/Ascendis-Pharma-Presents-New-Data-and-Updated-Results-from-Phase-1-2-IL-Believe-Trial-at-ASCO-2024.html [30] Scholar Rock Presents New Data from SRK-181 Phase 1 DRAGON Trial at ASCO 2024 Annual Meeting. Retrieved June 7, 2024, from https://www.businesswire.com/news/home/20240603004778/en [31] invoX Pharma Presents Positive Clinical Data from Phase 1 Study of FS222 in Patients with Advanced Solid Tumours at the 2024 American Society of Clinical Oncology Annual Meeting. Retrieved June 7, 2024, from https://www.businesswire.com/news/home/20240603068133/en [32] Eledon Presents Updated Data from Ongoing Phase 1b Trial Evaluating Tegoprubart for Prevention of Rejection in Kidney Transplantation. Retrieved June 7, 2024, from https://www.globenewswire.com/news-release/2024/06/03/2892558/0/en/Eledon-Presents-Updated-Data-from-Ongoing-Phase-1b-Trial-Evaluating-Tegoprubart-for-Prevention-of-Rejection-in-Kidney-Transplantation.html [33] ImmuneOncia Announces Biomarker Results from Phase 1 Clinical Trial of CD47 Antibody at ASCO. Retrieved June 7, 2024, from https://www.businesswire.com/news/home/20240603017832/en [34] Entera Bio Reports Phase 1 Clinical Data of First-in-Class, Oral PTH(1-34) Peptide Candidate (EB612) for Patients with Hypoparathyroidism at ENDO 2024. Retrieved June 7, 2024, from https://www.globenewswire.com/news-release/2024/06/03/2892199/0/en/Entera-Bio-Reports-Phase-1-Clinical-Data-of-First-in-Class-Oral-PTH-1-34-Peptide-Candidate-EB612-for-Patients-with-Hypoparathyroidism-at-ENDO-2024.html [35] Enlivex Receives Regulatory Authorization for the Initiation of a Placebo-Controlled Phase I/II Trial Evaluating Allocetra in Up To 46 Patients with Thumb Osteoarthritis. Retrieved June 7, 2024, from https://www.globenewswire.com/news-release/2024/06/03/2892206/0/en/Enlivex-Receives-Regulatory-Authorization-for-the-Initiation-of-a-Placebo-Controlled-Phase-I-II-Trial-Evaluating-Allocetra-in-Up-To-46-Patients-with-Thumb-Osteoarthritis.html [36] Indaptus Therapeutics Announces New Positive Data from Ongoing Phase 1 Trial of Decoy20. Retrieved June 7, 2024, from https://www.globenewswire.com/news-release/2024/06/03/2892212/0/en/Indaptus-Therapeutics-Announces-New-Positive-Data-from-Ongoing-Phase-1-Trial-of-Decoy20.html [37] Alkermes Presents Data From Phase 1b Study of ALKS 2680 Demonstrating Improved Wakefulness in Patients With Narcolepsy Type 1 at SLEEP 2024. Retrieved June 7, 2024, from https://www.prnewswire.com/news-releases/alkermes-presents-data-from-phase-1b-study-of-alks-2680-demonstrating-improved-wakefulness-in-patients-with-narcolepsy-type-1-at-sleep-2024-302161336.html [38] IDRx Reports Updated Preliminary Phase 1 Data from Ongoing Phase 1/1b StrateGIST 1 Trial Supporting Best-in-Class Potential for IDRX-42 in Patients with GIST. Retrieved June 7, 2024, from https://www.businesswire.com/news/home/20240531639390/en [39] Century Therapeutics Presents Interim Results from Phase 1 ELiPSE-1 Study at ASCO 2024 Annual Meeting. Retrieved June 7, 2024, from https://www.globenewswire.com/news-release/2024/06/03/2892097/0/en/Century-Therapeutics-Presents-Interim-Results-from-Phase-1-ELiPSE-1-Study-at-ASCO-2024-Annual-Meeting.html [40] MediciNova Announces Data from Phase 1b/2a Clinical Trial of MN-166 (ibudilast) in Glioblastoma Patients at the American Society of Clinical Oncology (ASCO) Annual Meeting 2024. Retrieved June 7, 2024, from https://www.globenewswire.com/news-release/2024/06/03/2892064/7767/en/MediciNova-Announces-Data-from-Phase-1b-2a-Clinical-Trial-of-MN-166-ibudilast-in-Glioblastoma-Patients-at-the-American-Society-of-Clinical-Oncology-ASCO-Annual-Meeting-2024.html [41] FibroGen Announces FDA Clearance of Investigational New Drug Application for FG-3165, a Galectin-9 Targeting Monoclonal Antibody, for the Treatment of Patients with Solid Tumors. Retrieved June 7, 2024, from https://www.globenewswire.com/news-release/2024/06/03/2892568/0/en/FibroGen-Announces-FDA-Clearance-of-Investigational-New-Drug-Application-for-FG-3165-a-Galectin-9-Targeting-Monoclonal-Antibody-for-the-Treatment-of-Patients-with-Solid-Tumors.html [42] STORM Therapeutics Presented Interim Phase 1 Clinical Data on its METTL3 RNA Methyltransferase Inhibitor STC-15 at ASCO 2024. Retrieved June 7, 2024, from https://www.prnewswire.com/news-releases/storm-therapeutics-presented-interim-phase-1-clinical-data-on-its-mettl3-rna-methyltransferase-inhibitor-stc-15-at-asco-2024-302160864.html [43] Black Diamond Therapeutics Presents Promising BDTX-1535 Clinical Data in Patients with Recurrent Glioblastoma at 2024 American Society of Clinical Oncology (ASCO) Annual Meeting. Retrieved June 7, 2024, from https://investors.blackdiamondtherapeutics.com/news-releases/news-release-details/black-diamond-therapeutics-presents-promising-bdtx-1535-clinical [44] Immunocore reports updated Phase 1 data of brenetafusp (IMC-F106C), an ImmTAC bispecific targeting PRAME, in immune checkpoint pre-treated cutaneous melanoma patients at ASCO 2024. Retrieved June 7, 2024, from https://www.globenewswire.com/news-release/2024/05/31/2891735/0/en/Immunocore-reports-updated-Phase-1-data-of-brenetafusp-IMC-F106C-an-ImmTAC-bispecific-targeting-PRAME-in-immune-checkpoint-pre-treated-cutaneous-melanoma-patients-at-ASCO-2024.html [45] Kymera Therapeutics Presents New Clinical Data from Ongoing Phase 1 Trial of MDM2 Degrader KT-253 at ASCO Annual Meeting. Retrieved June 7, 2024, from https://www.globenewswire.com/news-release/2024/06/01/2891812/0/en/Kymera-Therapeutics-Presents-New-Clinical-Data-from-Ongoing-Phase-1-Trial-of-MDM2-Degrader-KT-253-at-ASCO-Annual-Meeting.html [46] Accutar Biotechnology Presents Phase 1 Data of AC699 Monotherapy in Patients with ER+ / HER2- Breast Cancer at ASCO 2024. Retrieved June 7, 2024, from https://www.businesswire.com/news/home/20240601126229/en [47] Molecular Partners Presents Positive Data From Completed Phase 1 Trial Of MP0317 (FAP X CD40 DARPin) Monotherapy In Patients With Advanced Solid Tumors At ASCO 2024. Retrieved June 7, 2024, from https://www.globenewswire.com/news-release/2024/06/01/2891809/0/en/Molecular-Partners-Presents-Positive-Data-From-Completed-Phase-1-Trial-Of-MP0317-FAP-X-CD40-DARPin-Monotherapy-In-Patients-With-Advanced-Solid-Tumors-At-ASCO-2024.html [48] Updated Data from the Phase 1/2 Study of Olomorasib in KRAS G12C-Mutant Advanced Solid Tumors Presented at the 2024 ASCO® Annual Meeting. Retrieved June 7, 2024, from https://www.prnewswire.com/news-releases/updated-data-from-the-phase-12-study-of-olomorasib-in-kras-g12c-mutant-advanced-solid-tumors-presented-at-the-2024-asco-annual-meeting-302160829.html [49] ALX Oncology Presents First Evorpacept Combination Data with an Antibody-Drug Conjugate from Phase 1 ASPEN-07 Clinical Trial in Patients with Advanced Bladder Cancer. Retrieved June 7, 2024, from https://www.globenewswire.com/news-release/2024/06/02/2891851/0/en/ALX-Oncology-Presents-First-Evorpacept-Combination-Data-with-an-Antibody-Drug-Conjugate-from-Phase-1-ASPEN-07-Clinical-Trial-in-Patients-with-Advanced-Bladder-Cancer.html 免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。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：本文来自药明康德内容团队，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

临床结果基因疗法免疫疗法临床2期

2024-06-02

·GlobeNewswire-Health Care

ALX Oncology Presents First Evorpacept Combination Data with an Antibody-Drug Conjugate from Phase 1 ASPEN-07 Clinical Trial in Patients with Advanced Bladder Cancer

Evorpacept in combination with PADCEV®, an approved antibody-drug conjugate (“ADC”), demonstrated promising activity and was generally well toleratedCompany to host conference call and webcast with Samuel A. Funt, M.D., of Memorial Sloan Kettering Cancer Center on Friday, June 7, 2024, at 1:00 PM ET SOUTH SAN FRANCISCO, Calif., June 02, 2024 (GLOBE NEWSWIRE) -- ALX Oncology Holdings Inc., (“ALX Oncology” or “the Company”) (Nasdaq: ALXO), an immuno-oncology company developing therapies that block the CD47 immune checkpoint pathway, today presented data from its Phase 1 ASPEN-07 clinical trial in a poster presentation (abstract #4575) at the 2024 American Society of Cancer Oncology (“ASCO”) Annual Meeting being held in Chicago from May 31-June 4, 2024. These findings represent the first evorpacept combination data with an ADC from ASPEN-07’s ongoing, open-label, single-arm, clinical trial of evorpacept in combination with PADCEV (enfortumab vedotin or “EV”) in patients with locally advanced or metastatic urothelial cancer (“la/m UC”). Evorpacept is a CD47 blocker with an inactivated Fc effector domain that is designed to minimize associated toxicity. Key results as of the data cut-off date of April 3, 2024: Initial patient demographics Twenty-eight EV-naïve patients were enrolled with 29% having received three or more prior lines of therapy.All patients had disease that progressed after platinum chemotherapy and checkpoint inhibition.Approximately 93% of patients had metastatic disease. The combination was generally well-tolerated in a heavily pre-treated patient population No maximum tolerated dose was reached, and the maximum administered evorpacept dose was 30 mg/kg Q2W.There were no treatment-related deaths in the study.The most frequent adverse events due to any cause were low-grade fatigue, dysgeusia, nausea, diarrhea, hyperglycemia, and pruritis. Initial activity showed tumor reduction in the majority of evaluable patients ASCO poster presentation data-cut reported an unconfirmed overall response rate (“ORR”) of 59% (n=22) with evorpacept plus EV (EV single agent ORR benchmark is 41%1).Following the April data cut-off, four additional response evaluable patients yielded an unconfirmed ORR of 61% (n=26) including two confirmed complete responses and six confirmed partial responses. To date, 58% of evaluable patients remain in the study. Continued follow-up for patients who are EV-naïve on ASPEN-07 is ongoing and, enrollment of a new cohort of patients who have received prior EV has begun. “We are encouraged by the preliminary safety data and clinical activity of evorpacept combined with PADCEV in patients with advanced bladder cancer,” said Sophia Randolph, M.D., Ph.D., Chief Medical Officer of ALX Oncology. “To our knowledge, these data are the first demonstration of anti-tumor activity with a CD47 blocker and an ADC in a heavily pre-treated patient population in the clinical setting. With these promising early results, we are evaluating clinical development options in both PADCEV-naïve and experienced patient populations.” “This emerging dataset reported favorable potential for evorpacept to be combined with an ADC in a patient population that has exhausted many treatments,” said Jason Lettmann, Chief Executive Officer of ALX Oncology. “We are especially hopeful because of the two patients with confirmed complete responses, which further exhibited this combination is active and that responses could improve over time in more patients. Heading further into the year, we will continue the momentum for ASPEN-07 as we gear up to share multiple, randomized, Phase 2 clinical data readouts where evorpacept is combined with anti-cancer antibodies and checkpoint inhibitors.” The poster can be found on the Publications section of the ALX Oncology website here. Company Event with ASPEN-07 Principal Investigator and ALX Oncology ManagementThe Company is hosting a virtual event with key opinion leaders on Friday, June 7, 2024, at 1:00 PM ET. The event will feature leading ASPEN-07 principal investigator and bladder cancer expect, Samuel A. Funt, M.D., from Memorial Sloan Kettering Cancer Center, along with the management team of ALX Oncology. The discussion will cover details of the first promising initial dose escalation data from the Phase 1 ASPEN-07 clinical trial of evorpacept in combination with EV in patients with la/m UC, and how ASPEN-07 could fit into the treatment paradigm of this indication. Samuel A. Funt, M.D., is a genitourinary oncologist at Memorial Sloan Kettering Cancer Center in New York, NY, where he is also Director of the Inpatient Genitourinary Oncology Service, Director of Bladder Cancer Clinical Trials Operations, and member of the Data Safety Monitoring Committee. Dr. Funt has practiced medicine and been involved in clinical trials for over 10 years. His top areas of clinical expertise are Bladder and Testicular Cancers. Dr. Funt has co-authored over 60 peer-reviewed articles and been awarded research grants from the National Institutes Health, American Society of Clinical Oncology, and the American Cancer Society. His research focuses on the development of more personalized and effective treatments and novel biomarkers of therapeutic response and resistance. The event will be webcast live and can be accessed by visiting the Investors section of ALX Oncology’s website at www.alxoncology.com and selecting Events under News and Events. To participate in the live event, please register using this link: https://edge.media-server.com/mmc/p/ct2fpmxb. An archived webcast will be available following the event. About the Phase 1 Clinical Trial Investigating Evorpacept plus EV in Advanced Bladder Cancer The Phase 1 clinical trial is an ongoing, open-label, single arm is designed to evaluate the safety, tolerability, and efficacy of evorpacept in combination with EV in patients with la/m UC (NCT05524545). This dose escalation clinical trial has enrolled cohorts receiving 20 mg/kg Q2W or 30 mg/kg Q2W evorpacept plus standard EV treatment. The study is sponsored and conducted by ALX Oncology. About Bladder Cancer and UC As estimated by the National Cancer Institute, bladder cancer is the sixth most common cancer type in the United States. UC is the most common type of bladder cancer and accounts for approximately 90% of all bladder cancer cases. Roughly 83,000 new cases of bladder cancer will be diagnosed in the United States in 2024 with about 16,800 deaths. The five-year survival for patients with metastatic bladder cancer is less than 8%. Worldwide, over 614,000 new cases of bladder cancer and over 220,000 deaths occurred in 2022 according to The Global Cancer Observatory. About ALX Oncology ALX Oncology is a publicly traded, clinical-stage immuno-oncology company focused on helping patients fight cancer by developing therapies that block the CD47 immune checkpoint inhibitor and bridge the innate and adaptive immune system. ALX Oncology’s lead product candidate, evorpacept, is a next generation CD47 blocking therapeutic that combines a high-affinity CD47 binding domain with an inactivated, proprietary Fc domain. To date, evorpacept has been dosed in over 500 subjects and has demonstrated promising activity and favorable tolerability profile across a range of hematologic and solid malignancies in combination with various leading anti-cancer antibodies. ALX Oncology is currently focusing on combining evorpacept with anti-cancer antibodies, ADCs, and PD-1/PD-L1 immune checkpoint inhibitors. Evorpacept’s Unique Profile: Anchored by a Rational Design and Triple Development Pillars Rationally engineered with an inactive Fc effector function, evorpacept’s clinical data to date has demonstrated a substantially improved safety profile over other anti-CD47 molecules in the clinic with an active Fc (i.e., binding the Fc gamma receptor on macrophages). This best-in-class safety profile allows for higher dosage with minimal overlapping toxicity in the combination treatment setting. CD47 expressed on cancer cells binds to its receptor SIRP alpha, which is predominantly expressed on two cell types: macrophages and dendritic cells. The Company’s pipeline of therapeutic candidates with standard-of-care agents include: Anti-cancer antibodies and ADCs (the “don’t eat me” signal): evorpacept enables Fc-mediated antibody-dependent phagocytosis by macrophages in combination with anti-cancer antibodies (e.g., Herceptin®) and ADCs (e.g., PADCEV and ENHERTU®) with an active Fc domain, which is otherwise impaired by CD47 expression on cancer cells binding to SIRP alpha on macrophages. Additionally, ADCs target the delivery of a chemotherapeutic payload to tumor cells to exert cytotoxic effects.PD-1/PD-L1 immune checkpoint inhibitors (the “don’t activate T-cells” signal): evorpacept enables T-cell activation by dendritic cells that are constitutively inhibited by CD47 expression on cancer cells binding to SIRP alpha on dendritic cells. Activated dendritic cells present neoantigens to T-cells that once activated will kill cancer cells when the PD-1/PD-L1 inhibitory interaction is blocked by T-cell checkpoint inhibitors. References 1 Powles, et al, NEJM 2021; Powles, et al, Genitourinary Cancer Symposium 2021 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.

临床1期临床结果ASCO会议免疫疗法

2024-05-09

·精准药物

创新靶点的崛起与黯淡

PREFACE前言创新药的研发总是伴随着不确定性。一边海水，一边火焰，如履薄冰。一批曾经备受关注的靶点最终悄然沉寂，似卷着过往而远，无不令人唏嘘。这样的靶点很多，不胜枚举，譬如CD47、TIGIT、TIM-3、TGF-β等，"眼看他起朱楼,眼看他宴宾客,眼看他楼塌了。"本文通过盘点曾经盛极一时、又悄然而去的“明星”靶点，为创新药研发提供参考。01CD47血液毒性的难言之隐CD47是一种广泛表达的跨膜糖蛋白，可与巨噬细胞表面信号调节蛋白α（SIRPα）的N末端结合，并发出“别吃我”（Don’t eat me）信号，抑制巨噬细胞的吞噬作用。当细胞老化或病变时，细胞表面的CD47逐渐丧失，衰老或病变的细胞由此被巨噬细胞吞噬。但狡猾的肿瘤细胞也盯上了这一条“保命”通路，通过高表达CD47，肿瘤细胞向巨噬细胞发出“别吃我”信号，抑制巨噬细胞的吞噬作用，进而实现免疫逃逸。由于CD47在许多肿瘤细胞表面均高表达，利用单克隆抗体、融合蛋白或双特异性抗体来阻断CD47-SIRPα间的信号通路，恢复巨噬细胞对肿瘤细胞的吞噬作用是肿瘤免疫治疗的重要发展方向之一。 CD47与SIRP-α通路图示资料来源：SIRPα–CD47 Immune Checkpoint Blockade in Anticancer Therapy尽管CD47和SIRPα通路抗癌原理清晰，但由于CD47同样表达于正常细胞表面（尤其是红细胞），因此，CD47抗体的脱靶毒性（On target，Off tumor）始终是一个隐患。由于红细胞表面也高表达CD47，一旦CD47抗体与红细胞表面的CD47结合，可引起红细胞凝集，进而导致红细胞裂解。2017年，由于患者出现红细胞凝集而死亡的问题，Tioma公司终止了CD47单抗Ti-061的临床研究。2018年，Celgene的CC-90002也因遭遇严重不良事件而中止了药物的临床研究。尽管后续企业持续探索CD47的改进方案，包括改良给药方式（低剂量诱导）、降低药物与红细胞的结合能力、结合独特抗原表位等。但CD47有限的疗效更是成为了压倒骆驼的最后一根稻草，2023年，吉利德就宣布终止CD47单抗Magrolimab联合阿扎胞苷一线治疗高危骨髓增生异常综合征（MDS）的III期临床ENHANCE失败。2023年8月10日，凭借CD47管线纳斯达克上市的ALX Oncology宣布终止核心管线SIRPα融合蛋白Evorpacept治疗MDS、AML的临床研究。2023年9月22日，艾伯维终止与天镜生物就CD47抗体lemzoparlimab的合作协议。2024年2月，吉利德终止magrolimab用于治疗急性髓性白血病（AML）的III期ENHANCE-3研究，在该分析中，magrolimab联合阿扎胞苷和venetoclax无治疗效果，并观察到死亡风险增加，主要由感染和呼吸衰竭引起。但CD47/SIRPα的故事并未结束，2023年10月份传来Evorpacept在治疗HER2阳性胃或胃食管交界处癌的II期研究中取得积极结果的消息，次日ALX Oncology股价大涨56%。或许实体瘤才是CD47的最后救赎？让我们拭目以待。02TIGIT惨遭滑铁卢，一线肝细胞癌赋予新希望 TIGIT是脊髓灰质炎病毒受体（PVR）/Nectin家族的成员，常表达于记忆T细胞、调节T细胞、滤泡辅助细胞及NK细胞。TIGIT由细胞外免疫球蛋白可变区（IgV）结构域，1型跨膜结构域和具有经典免疫受体酪氨酸抑制基序和免疫球蛋白酪氨酸尾基序的细胞内结构域组成。2020年，因tiragolumab出色的Ⅱ期临床数据，TIGIT一度被业内人士称为“下一个PD-1”。但自2022年以来，TIGIT单抗惨遭滑铁卢。2022年3月，罗氏宣布tiragolumab（TIGIT单抗）一线治疗小细胞肺癌的III期临床SKYSCRAPER-02研究未能达到无进展生存期（PFS）共同主要终点，在中期分析中没有达到总生存期（OS）的主要终点。2022年5月，罗氏宣布tiragolumab联合PD-L1一线治疗非小细胞肺癌三期临床SKYSCRAPER-01未达到无进展生存期的主要终点。2023年3月，默沙东宣布 PD-1+TIGIT 复方制剂 MK-7684A 治疗转移性非小细胞肺癌（NSCLC）的 II 期非注册 KeyVibe-002 研究的最新结果未达预期。尽管TIGIT近年来数据不甚靓眼，但一线肝癌赋予了TIGIT新的希望。Tiragolumab联合阿替利珠单抗（atezo）和贝伐珠单抗（bev）一线治疗不可切除、局部晚期或转移性肝细胞癌（uHCC）。58名患者被随机分组（tira + atezo + bev组，n=40；atezo + bev组，n=18）。截至2022年11月28日，ORR分别为42.5% vs. 11.1%；中位无进展生存期（PFS）分别为11.1m vs 4.2m（HR=0.42）。03TIM-3诺华剔除TIM-3单抗，GSK继续推进TIM3全称为T cell immunoglobulin and mucin domain-containing protein 3，于2002年首次被发现，是免疫调节蛋白TIM家族的一员。2016年，在免疫治疗靶点PD-1发展“如日中天”之时，Nature Reviews发表了一篇题为“PD-1 says goodbye, TIM-3 says hello”的文章，让诸多研究者关注到了TIM3这一免疫治疗靶点。然而，TIM-3靶点的研发并不如PD-1般顺利，作为单药，TIM3抗体没有实质性的临床益处，于是研究者将目光投向联用的治疗。然而，2024年1月，诺华在2023年财报中更新了其TIM-3单抗sabatolimab（MBG453）联合治疗中度、高或极高风险骨髓增生异常综合征（MDS）或慢性粒单核细胞白血病-2（CMML-2）的III期STIMULUS MDS2研究未达到总生存期（OS）的主要终点。基于此，诺华已将其从管线中剔除。但GSK仍在推进旗下TIM-3管线cobolimab与PD-1单抗Dostarlimab联用的Ⅱ/Ⅲ期临床，布局的适应症包括末线黑色素瘤和末线非小细胞肺癌等。目前，cobolimab联合Dostarlimab在实体瘤上展现出初步的疗效。04TGF-β默克终止M7824的研发转化生长因子β（TGF-β）是一种有效的多效性细胞因子，在肿瘤发生中具有复杂的、相互矛盾的作用。临床前的研究表明，阻断TGF-β信号是治疗肿瘤的有效方法，它能减轻Treg介导的免疫抑制，增加T细胞毒性，促进T细胞向肿瘤中心的渗透，从而引起强烈的抗肿瘤免疫和肿瘤消退。此外，阻断TGF-β信号增强了肿瘤对免疫检查点抑制剂（ICI）的反应。尽管临床前研究效果良好，但临床的实际疗效却给了研究者当头一棒。2021年，默克旗下的TGF-β/PD-L1双功能融合蛋白bintrafusp alfa（M7824）接连失败，先是在1月宣布终止肺癌的三期临床，紧接着在3月宣布单药二线治疗局部晚期或转移性胆道癌疗效不佳，随后于8月宣布终止M7824一线治疗胆管癌的临床研究，接连的失败为TGF-β蒙上了阴影。最终，于2021年9月，默克与GSK达成协议，终止关于bintrafusp alfa（M7824）的合作。目前，恒瑞仍在积极推动旗下SHR-1701（PD-L1×TGF-βRⅡ双功能融合蛋白）的临床研究，在2023ASCO上，SHR-1701联合SHR2554（EZH2抑制剂）治疗末线cHL展现出良好的临床获益，此外，SHR-1701正在探索诸多实体瘤适应症，包括胃癌、宫颈癌等。SUMMARY小结医药研发可谓如履薄冰，根据Pharmapremia基于近一万项临床试验的统计数据，Ⅰ、Ⅱ、Ⅲ期临床研究的成功率分别是63.8%、33.2%和60.1%。其中Ⅱ期临床失败率最高，成功率仅33.2%；即便通过了Ⅱ期临床试验，Ⅲ期临床试验的成功率也仅为60.1%。因此，对于医药企业而言，一方面要做到靶点差异化，努力实现人无我有，人有我优；另一方面，聚焦成药性高的靶点，加速研发，最终实现弯道超车的目的。声明：发表/转载本文仅仅是出于传播信息的需要，并不意味着代表本公众号观点或证实其内容的真实性。据此内容作出的任何判断，后果自负。若有侵权，告知必删！长按关注本公众号粉丝群/投稿/授权/广告等请联系公众号助手觉得本文好看，请点这里↓

临床3期免疫疗法

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表达胃食管交界处腺癌	临床3期	美国	ALX Oncology, Inc.	2022-01-15
HER2表达胃食管交界处腺癌	临床3期	日本	ALX Oncology, Inc.	2022-01-15
HER2表达胃食管交界处腺癌	临床3期	比利时	ALX Oncology, Inc.	2022-01-15
HER2表达胃食管交界处腺癌	临床3期	捷克	ALX Oncology, Inc.	2022-01-15
HER2表达胃食管交界处腺癌	临床3期	法国	ALX Oncology, Inc.	2022-01-15
HER2表达胃食管交界处腺癌	临床3期	意大利	ALX Oncology, Inc.	2022-01-15
HER2表达胃食管交界处腺癌	临床3期	新加坡	ALX Oncology, Inc.	2022-01-15
HER2表达胃食管交界处腺癌	临床3期	韩国	ALX Oncology, Inc.	2022-01-15
HER2表达胃食管交界处腺癌	临床3期	西班牙	ALX Oncology, Inc.	2022-01-15
HER2表达胃食管交界处腺癌	临床3期	中国台湾	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


NCT05524545 (ASCO2024)	临床1期	转移性尿路上皮癌	20	Evorpacept 20 mg/kg	簾艱願積夢夢簾窪積壓(鹹窪觸鏇壓餘簾鏇鑰網) = 1 pt 簾選蓋憲繭構糧鹹願鏇 (繭壓糧壓淵築觸製壓餘 ) 更多	积极	2024-05-24
				Enfortumab vedotin
NCT05167409 (phase 2 study of evorpacept (E, ALX148), cetuximab (C), and pembrolizumab (P), ASCO2024)	临床2期	转移性微卫星稳定结直肠癌	16	Evorpacept (E) 15 mg/kg	蓋齋構艱餘網膚餘壓淵(衊餘選選窪鬱鏇鑰觸壓) = 憲簾壓廠構鏇憲齋餘糧膚網夢範醖鑰艱鑰膚齋 (壓膚鬱網餘憲觸餘觸觸, 0.2 ~ 30.2) 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	獵構構構衊鑰膚製鬱網(鏇製鹹簾築廠襯範鑰餘) = 簾壓蓋鏇構齋構壓網願齋遞築範廠膚觸網壓選 (醖獵簾襯鹽簾範遞餘夢 ) 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	淵網觸艱製簾膚窪鬱選(衊糧鑰顧憲製繭願製鹽) = 襯鹹鏇遞糧蓋簾淵醖遞積蓋構憲鏇壓膚製憲艱 (窪蓋構製艱鹹構衊鏇糧 ) 更多	积极	2023-10-03
				trastuzumab + CYRAMZA + paclitaxel	淵網觸艱製簾膚窪鬱選(衊糧鑰顧憲製繭願製鹽) = 鏇廠選觸顧齋鬱觸憲觸積蓋構憲鏇壓膚製憲艱 (窪蓋構製艱鹹構衊鏇糧 ) 更多
NCT04755244 (ASPEN-05, ASH2022) 人工标引	临床1/2期	急性髓性白血病	14	Evorpacept+Venetoclax+Azacitidine	餘顧積顧構餘憲艱範顧(壓蓋構觸顧構衊願築願) = 衊鑰廠鹽窪獵衊遞糧憲鑰網鬱醖糧鏇窪憲遞網 (鹹齋網廠顧顧齋鏇夢積 )	积极	2022-11-15
NCT04417517 (ASPEN-02, ASH2021) 人工标引	临床1/2期	骨髓增生异常综合征一线	13	azacitidine+evorpacept	壓鏇鹽顧蓋獵憲鑰艱蓋(壓壓願鬱築積齋製觸糧) = No DLTs were observed in any cohort. 鹹選醖壓顧築壓鏇構鑰 (構積夢觸繭鏇壓鹹構製 ) 更多	积极	2021-11-05
				azacitidine
NCT03013218 (ASPEN-01, ESMO_GI2021)	临床1期	HER2阳性胃食管交界处癌二线 trastuzumab	18	ALX148 15 mg/kg QW + Trastuzumab + Ramucirumab + Paclitaxel	餘繭糧遞蓋鹹獵壓鏇選(製選淵壓艱願鏇構夢製) = grade 3 decreased lymphocytes 獵網襯鬱繭餘鹹鬱製膚 (齋憲鑰窪範構齋願憲齋 )	积极	2021-07-03
EHA2020	临床1期	难治性非霍奇金淋巴瘤	-	ALX148 10 mg/kg QW + rituximab	膚築衊齋製襯簾襯顧艱(糧選襯醖鹹積齋齋鬱鑰) = Twenty-six pts experienced any AE 遞窪築選範獵艱艱觸觸 (壓獵鬱選膚積願衊構蓋 ) 更多	积极	2020-05-14
				ALX148 15 mg/kg QW + rituximab