TACTI-004, a Double-Blinded, Randomized Phase 3 Trial in Patients With Advanced/Metastatic Non-Small Cell Lung Cancer (NSCLC) Receiving Eftilagimod Alfa (MHC Class II Agonist) in Combination With Pembrolizumab (PD-1 Antagonist) and Chemotherapy.

The purpose of this study is to compare eftilagimod alfa (efti) in combination with pembrolizumab and chemotherapy versus placebo in combination with pembrolizumab and chemotherapy with respect to overall survival (OS) and progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) among adults with metastatic non-small cell lung cancer (NSCLC).
Participants will receive either efti plus standard treatment (pembrolizumab and platinum doublet chemotherapy) or placebo plus standard treatment and will be treated for up to 2 years.

开始日期2025-03-21

申办/合作机构

Immutep SAS

[+1]

NCT06128863

/ Active, not recruiting临床2期IIT

Phase II, Single-arm Clinical Trial Evaluating Efficacy and Safety of Pembrolizumab in Combination with a Soluble LAG-3 Protein, Eftilagimod Alpha, and Radiotherapy in Neoadjuvant Treatment of Patients with Soft Tissue Sarcomas (EFTISARC-NEO)

This is a phase II single-arm single-stage study evaluating efficacy and safety of pembrolizumab in combination with a soluble LAG-3 protein, eftilagimod alpha (Efti) and radiotherapy in neoadjuvant treatment of patients with soft tissue sarcomas. This study will determine the pathologic response rate (defined as percentage of tumor hyalinization/fibrosis) to the combination treatment.

开始日期2023-07-17

申办/合作机构

Maria Sklodowska-Curie National Research Institute of Oncology

[+1]

NCT04252768

/ Withdrawn临床1期

AIPAC-002 (Active Immunotherapy PAClitaxel-002): A Multicentre, Phase Ib Study to Test a New Schedule of Eftilagimod Alpha (a Soluble LAG-3 Protein) as Adjunctive to Weekly Paclitaxel in Hormone Receptor-positive Metastatic Breast Carcinoma Patients

This is a multicentre, multinational Phase Ib study in female HR+ MBC patients not receiving Her2-targeted therapy. Treatment consists of a chemo-immunotherapy phase followed by a maintenance phase. The chemo-immunotherapy phase consists of 6 cycles of 4 weeks each. During each cycle the subject will receive 80 mg/m2 paclitaxel intravenously on Day 1, 8 and 15 and 30 mg efti subcutaneously on Day 1 and 15 in a 28-day (4-week) cycle. Efti will always be given after paclitaxel. The maintenance phase comprises 6 visits with 4 weekly intervals; during each such visit 30 mg efti is given subcutaneously as monotherapy. A total of 24 subjects will be enrolled into the study. The primary goal of the study is safety and tolerability profile of efti in combination with weekly paclitaxel both given the same day in contrast to subsequent days as in the AIPAC trial.

开始日期2023-06-01

申办/合作机构

Immutep SAS

100 项与重组人源淋巴细胞激活基因-3（hLAG-3）融合蛋白(Immutep) 相关的临床结果

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100 项与重组人源淋巴细胞激活基因-3（hLAG-3）融合蛋白(Immutep) 相关的转化医学

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100 项与重组人源淋巴细胞激活基因-3（hLAG-3）融合蛋白(Immutep) 相关的专利（医药）

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项与重组人源淋巴细胞激活基因-3（hLAG-3）融合蛋白(Immutep) 相关的文献（医药）

2024-11-01·JTO clinical and research reports

Eftilagimod Alpha (a Soluble LAG-3 Protein) Combined With Pembrolizumab in Second-Line Metastatic NSCLC Refractory to Anti–Programmed Cell Death Protein 1/Programmed Death-Ligand 1-Based Therapy: Final Results from a Phase 2 Study

Article

作者: Roxburgh, Patricia ; Krebs, Matthew G. ; Majem, Margarita ; Clay, Tim ; Mueller, Christian ; Andres, B. ; Doger, Bernard ; Krebs, Matthew G ; Triebel, F. ; Doger, B. ; Forster, Martin ; Triebel, Frédéric ; Majem, M. ; Forster, M. ; Iams, W. ; Clay, T. ; Bajaj, P. ; Iams, Wade ; Perera, Suvini ; Peguero, J. ; Mueller, C. ; Bajaj, Pawan ; Krebs, M.G. ; Barba, Andres ; Roxburgh, P. ; Perera, S. ; Peguero, Julio

Introduction:

Eftilagimod alpha (efti), a soluble lymphocyte activation gene-3 protein, triggers antigen-presenting cell and T-cell (CD4⁺ and CD8⁺) activation and helps overcome resistance to programmed cell death protein 1 or programmed cell death-ligand 1 (PD-(L)1) inhibitors. We assessed efti plus pembrolizumab in second-line anti-PD-(L)1-refractory metastatic patients with NSCLC.

Methods:

After confirmed progression on anti-PD-(L)1-based first-line therapy, patients received efti (30 mg subcutaneously every 2 weeks for eight 3-week cycles and then every 3 weeks for up to 54 weeks) plus pembrolizumab (200 mg intravenously every 3 weeks for up to 105 weeks). The primary endpoint was the objective response rate by modified Response Evaluation Criteria in Solid Tumors version 1.1 for immune-based therapies. Secondary endpoints included disease control rate, progression-free survival, overall survival (OS), and tolerability. Exploratory endpoints included tumor growth kinetics and predefined subgroup analyses. Programmed cell death-ligand 1 tumor proportion score was assessed centrally.

Results:

Thirty-six patients were enrolled from April 2019 to August 2021 using Simon's two-stage design. Most patients (81.8%) had low or negative (<50%) PD-(L)1 tumor proportion score. First-line therapy was anti-PD-(L)1-based for all patients, combined with chemotherapy for 66.7%. The confirmed objective response and disease control rates were 8.3% and 33.3%. The median progression-free survival was 2.1 months and the median OS was 9.9 months. Patients exhibiting high PD-(L)1 expression or acquired resistance to PD-(L)1 inhibitors revealed superior response and survival outcomes, and OS was closely correlated with disease control. No treatment-emergent adverse event led to permanent discontinuation of study treatment.

Conclusions:

Efti plus pembrolizumab was well-tolerated and revealed signs of antitumor activity in patients with NSCLC resistant to PD-(L)1 inhibitors, warranting further investigation. Trial registration number: NCT03625323.

2024-09-03·CLINICAL CANCER RESEARCH

Eftilagimod Alpha (Soluble LAG3 Protein) Combined with Pembrolizumab as Second-Line Therapy for Patients with Metastatic Head and Neck Squamous Cell Carcinoma

Article

作者: Patel, Grisma ; Pousa, Antonio L. ; Roxburgh, Patricia ; Bajaj, Pawan ; Brignone, Chrystelle ; Mueller, Christian ; Krebs, Matthew ; Doger, Bernard ; Forster, Martin ; Triebel, Frederic ; Peguero, Julio ; Brana, Irene ; Carcereny, Enric

Abstract:

Purpose::

Eftilagimod alpha (efti), a soluble LAG3 protein, activates antigen-presenting cells (APC) and downstream T cells. TACTI-002 (part C) evaluated whether combining efti with pembrolizumab led to strong antitumor responses in patients with second-line recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) while demonstrating good tolerability.

Patients and Methods::

In this multinational phase II trial using Simon’s two-stage design, patients who were PD-L(1)-naïve with R/M HNSCC who had failed first-line platinum-based therapy, unselected for PD-L1, received intravenous pembrolizumab (200 mg, once every 2 weeks) combined with subcutaneous efti (30 mg once every 2 weeks for 24 weeks and once every 3 weeks thereafter). The primary endpoint was objective response rate per RECIST 1.1 modified for immune-based therapy by investigator assessment. Additional endpoints included duration of response, progression-free survival, overall survival, and tolerability. Pharmacodynamic effects (absolute lymphocyte count) and Th1 cytokine biomarkers (IFNγ/CXCL10)] were evaluated in liquid biopsies.

Results::

Between March 2019 and January 2021, 39 patients were enrolled; 37 were evaluated for response. All patients received prior chemotherapy, and 40.5% were pretreated with cetuximab; 53.1% of patients had PD-L1 combined positive score <20. With a median follow-up of 38.8 months, the objective response rate was 29.7%, including 13.5% complete responders. The median duration of response was not reached. Rapid and sustained absolute lymphocyte count increase was observed in patients who had an objective response. Th1 biomarkers increased sustainably after first treatment. No unexpected safety signals were observed.

Conclusions::

Efti plus pembrolizumab was safe and showed encouraging antitumor activity and pharmacodynamic effects in patients with second-line head and neck squamous cell carcinoma (HNSCC), thus supporting further evaluation of this combination in earlier treatment lines.

2024-02-01·Clinical cancer research : an official journal of the American Association for Cancer Research

Paclitaxel plus Eftilagimod Alpha, a Soluble LAG-3 Protein, in Metastatic, HR+ Breast Cancer: Results from AIPAC, a Randomized, Placebo Controlled Phase IIb Trial

Article

作者: Perjesi, Luca ; Dalenc, Florence ; Pápai, Zsuzsanna ; Brignone, Chrystelle ; Duhoux, Francois P. ; Armstrong, Anne ; Marme, Frederik ; Kuemmel, Sherko ; Jager, Agnes ; Dirix, Luc ; Cuypere, Eveline ; Triebel, Frederic ; Wildiers, Hans ; Schröder, Carolina P. ; Mueller, Christian ; Vuylsteke, Peter ; Menke-van der Houven van Oordt, Catharina Willemien ; Chan, Steve ; Huober, Jens ; Brain, Etienne

Abstract:

Purpose::

Eftilagimod alpha (efti), a soluble lymphocyte activation gene (LAG-3) protein and MHC class II agonist, enhances innate and adaptive immunity. Active Immunotherapy PAClitaxel (AIPAC) evaluated safety and efficacy of efti plus paclitaxel in patients with predominantly endocrine-resistant, hormone receptor–positive, HER2-negative metastatic breast cancer (ET-resistant HR+ HER2− MBC).

Patients and Methods::

Women with HR+ HER2– MBC were randomized 1:1 to weekly intravenous paclitaxel (80 mg/m2) and subcutaneous efti (30 mg) or placebo every 2 weeks for six 4-week cycles, then monthly subcutaneous efti (30 mg) or placebo maintenance. Primary endpoint was progression-free survival (PFS) by blinded independent central review. Secondary endpoints included overall survival (OS), safety/tolerability, pharmacokinetics/pharmacodynamics, and quality of life. Exploratory endpoints included cellular biomarkers.

Results::

114 patients received efti and 112 patients received placebo. Median age was 60 years (91.6% visceral disease, 84.1% ET-resistant, 44.2% with previous CDK4/6 inhibitor treatment). Median PFS at 7.3 months was similar for efti and placebo. Median OS was not significantly improved for efti (20.4 vs. 17.5 months; HR, 0.88; P = 0.197) but became significant for predefined exploratory subgroups. EORTC QLQC30-B23 global health status was sustained for efti but deteriorated for placebo. Efti increased absolute lymphocyte, monocyte and secondary target cell (CD4, CD8) counts, plasma IFNγ and CXCL10 levels.

Conclusions::

Although the primary endpoint, PFS, was not met, AIPAC confirmed expected pharmacodynamic effects and demonstrated excellent safety profile for efti. OS was not significantly improved globally (2.9-month difference), but was significantly improved in exploratory biomarker subgroups, warranting further studies to clarify efti's role in patients with ET-resistant HER2− MBC.

205

项与重组人源淋巴细胞激活基因-3（hLAG-3）融合蛋白(Immutep) 相关的新闻（医药）

2025-05-29

·GlobeNewswire-Health Care

Immutep’s Efti with Radiotherapy & KEYTRUDA® (pembrolizumab) Meets Primary Endpoint in Phase II for Soft Tissue Sarcoma

Novel combination with efti has met the trial’s primary endpoint of tumour hyalinization/fibrosis in the neoadjuvant setting for patients with resectable soft tissue sarcoma Detailed results are planned for presentation at a future medical meeting May 27, 2025 -- Immutep Limited (ASX: IMM; NASDAQ: IMMP) (“Immutep” or “the Company”), a late-stage immunotherapy company targeting cancer and autoimmune diseases, today announces the investigator-initiated EFTISARC-NEO Phase II trial evaluating eftilagimod alfa (efti) with radiotherapy plus KEYTRUDA® (pembrolizumab) in the neoadjuvant setting for resectable soft tissue sarcoma (STS) has met its primary endpoint. The novel combination significantly exceeded the study’s prespecified median of 35% tumour hyalinization/fibrosis versus 15% for historical data from radiotherapy alone in patients with resectable soft tissue sarcoma (STS). Tumour hyalinization/fibrosis is an early surrogate endpoint at the time of surgical resection that has been associated with improved overall survival and recurrence-free survival for STS patients.1,2 The trial’s investigators at the Maria Skłodowska-Curie National Research Institute of Oncology (MSCNRIO) in Warsaw, the national reference centre for STS in Poland, plan to present detailed results from the study at a future medical meeting. Katarzyna Kozak, M.D., Ph.D., and Paweł Sobczuk, M.D., Ph.D., medical oncologists at the Department of Soft Tissue/Bone Sarcoma and Melanoma at MSCNRIO and the trial’s principal investigators, said: “It is very encouraging to see the chemotherapy-free combination with efti far exceed the ambitious target we initially set for the trial's primary endpoint in resectable soft tissue sarcoma. These results support our belief that efti's activation of antigen-presenting cells, and in turn a broad adaptive and innate immune response, helps transform the immunosuppressed tumour microenvironment of soft tissue sarcomas leading to strong anti-cancer efficacy. There remains a very high unmet need in this aggressive orphan cancer indication and we look forward to presenting detailed results at a medical meeting later this year.” As previously announced at the Connective Tissue Oncology Society (CTOS) Annual Meeting in November 2024, the combination therapy demonstrated significant efficacy with a median of 50% tumour hyalinization/fibrosis in a preliminary analysis of 21 patients with resectable STS available for primary endpoint assessment. The EFTISARC-NEO study, which is primarily funded with a grant from the Polish government awarded by the Polish Medical Research Agency program, subsequently completed enrolment of 40 patients in January 2025. STS is an orphan disease with high unmet medical need and a poor prognosis for patients. The incidence of STS varies in different regions globally. In the United States, the number of new STS cases in 2025 is estimated to be ~13,520 with ~5,420 deaths, according to the American Cancer Society.3 Efti is Immutep’s proprietary soluble LAG-3 protein and MHC Class II agonist that stimulates both innate and adaptive immunity for the treatment of cancer. As a first-in-class antigen presenting cell (APC) activator, efti binds to MHC (major histocompatibility complex) Class II molecules on APC leading to activation and proliferation of CD8+ cytotoxic T cells, CD4+ helper T cells, dendritic cells, NK cells, and monocytes. It also upregulates the expression of key biological molecules like IFN-ƴ and CXCL10 that further boost the immune system’s ability to fight cancer. Efti is under evaluation for a variety of solid tumours including non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), and metastatic breast cancer. Its favourable safety profile enables various combinations, including with anti-PD-[L]1 immunotherapy and/or chemotherapy. Efti has received Fast Track designation in first line HNSCC and in first line NSCLC from the United States Food and Drug Administration (FDA). Immutep is a late-stage biotechnology company developing novel immunotherapies for cancer and autoimmune disease. The Company is a pioneer in the understanding and advancement of therapeutics related to Lymphocyte Activation Gene-3 (LAG-3), and its diversified product portfolio harnesses LAG-3’s ability to stimulate or suppress the immune response. Immutep is dedicated to leveraging its expertise to bring innovative treatment options to patients in need and to maximise value for shareholders. For more information, please visit www.immutep.com. 1. Schaefer IM et al. Histologic Appearance After Preoperative Radiation Therapy for Soft Tissue Sarcoma: Assessment of the European Organization for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group Response Score. Int J Radiat Oncol Biol Phys. 2017 Jun 1;98(2):375-383. doi: 10.1016/j.ijrobp.2017.02.087. Epub 2017 Feb 24. PMID: 28463157. 2. Rao SR et al. Extent of tumor fibrosis/hyalinization and infarction following neoadjuvant radiation therapy is associated with improved survival in patients with soft-tissue sarcoma. Cancer Med. 2022 Jan;11(1):194-206. doi: 10.1002/cam4.4428. Epub 2021 Nov 27. PMID: 34837341; PMCID: PMC8704179. 3. American Cancer Society statistics: https://www.cancer.org/cancer/types/soft-tissue-sarcoma/about/key-statistics.html The content above comes from the network. if any infringement, please contact us to modify.

临床结果免疫疗法快速通道孤儿药

2025-05-15

·GlobeNewswire-Health Care

Immutep’s Efti with KEYTRUDA® (pembrolizumab) & Chemotherapy Achieves High Response Rates in First-Line Non-Small Cell Lung Cancer

Novel combination achieves 60.8% response rate and 90.2% disease control rate in first-line non-small cell lung cancer (1L NSCLC)Notably, ~92% of all evaluable patients have PD-L1 TPS <50%, including 43% with PD-L1 below 1 (TPS <1%), who represent an area of high unmet needData demonstrates significant improvement in response rates compared to historical controls, and safety continues to be favourableMulti-centre INSIGHT-003 is evaluating the same immunotherapy/chemotherapy combination used in the pivotal TACTI-004 Phase III in 1L NSCLCAdditional data from INSIGHT-003 is planned for presentation at a medical conference later this year SYDNEY, AUSTRALIA, May 15, 2025 (GLOBE NEWSWIRE) -- Immutep Limited (ASX: IMM; NASDAQ: IMMP) (“Immutep” or “the Company”), a late-stage immunotherapy company targeting cancer and autoimmune diseases, today announces that a 60.8% response rate and 90.2% disease control rate, according to RECIST1.1, has been achieved in the investigator-initiated INSIGHT-003 trial as of the data-cut off date of 06 May 2025. INSIGHT-003 is evaluating eftilagimod alpha (efti) in combination with the anti-PD-1 therapy, KEYTRUDA® (pembrolizumab) and doublet chemotherapy as first-line treatment for patients with advanced or metastatic non-squamous non-small cell lung cancer (1L NSCLC). Marc Voigt, CEO of Immutep, stated, “Our level of confidence in efti driving a new standard of care for patients with non-small cell lung cancer via our pivotal TACTI-004 trial continues to rise with the strength of the data from INSIGHT-003 and TACTI-002. Across two trials we have now efficacy data from 165 patients with 1L NSCLC who have been treated with efti and KEYTRUDA, either with or without chemotherapy. In multi-national settings, efti has generated consistent and remarkable improvements in response rates. In particular, the interim ORR data in patients with PD-L1 expression below 50% in the ongoing INSIGHT-003 trial, who represent over two-thirds of the 1L NSCLC patient population, is very encouraging.” Majority of Patients have PD-L1 TPS <50%Notably, ~92% of all evaluable patients (N=51) in the INSIGHT-003 study have PD-L1 TPS <50%. This includes 49% of patients with PD-L1 Tumour Proportion Score (TPS) of 1-49% and 43% of patients with PD-L1 TPS <1%, as shown in the table below. Strong Response Rates Across All PD-L1 Expression LevelsData from all evaluable patients demonstrates significant improvement of Overall Response Rate (ORR) according to RECIST 1.1 across all levels of PD-L1 expression compared to historical control from a registrational trial of anti-PD-1 and doublet chemotherapy in non-squamous 1L NSCLC1: 75.0% ORR versus 62.1% ORR in patients with high PD-L1 expression (TPS >50%)64.0% ORR versus 49.2% ORR in patients with low PD-L1 expression (TPS 1-49%)54.5% ORR versus 32.3% ORR in patients with negative PD-L1 expression (TPS <1%) The 60.8% response rate regardless of PD-L1 expression (TPS 0-100%) represents a substantial improvement compared to historical control of 48.0%.1 The relative outperformance is particularly strong given the registrational trial has four times as many patients with high PD-L1 expression (~32% of patients versus ~8% in INSIGHT-003), who have the highest response rates. Importantly, in patients with TPS <50% (N=47), who have a high unmet need and represent over two-thirds of the 1L NSCLC patient populaton, the triple combination with efti achieved a 59.6% response rate as compared to historical control of 40.8%.1 INSIGHT-003 Overall Response Rate & Disease Control Rate, according to RECIST1.1PD-L1 Expression LevelsTPS 0-100%(N=51)TPS <1%(N=22)TPS 1-49%(N=25)TPS <50%(N=47)TPS ≥50%(N=4)ORR %60.854.564.059.675.0DCR %90.286.492.089.4100 SafetySafety continues to be favourable for the triple combination in 1L NSCLC with no new safety signals. Next StepsAdditional data updates from this trial are expected to be presented at a medical conference in 2025 and beyond. About INSIGHT-003INSIGHT-003 is an investigator-initiated study conducted by the Frankfurt Institute of Clinical Cancer Research IKF and several other German centres. It is being run as the third arm (Stratum C) of the ongoing Phase I INSIGHT trial with Prof. Dr. Salah-Eddin Al-Batran as lead investigator. The study is evaluating a triple combination therapy in front-line non-small cell lung cancer patients consisting of efti administered subcutaneously in conjunction with an existing approved standard-of-care combination of anti-PD-1 therapy (pembrolizumab) and chemotherapy (carboplatin and pemetrexed) delivered intravenously. The trial will assess the safety, tolerability, and initial efficacy of the combination. About Eftilagimod Alfa (efti)Efti is Immutep’s proprietary soluble LAG-3 protein and MHC Class II agonist that stimulates both innate and adaptive immunity for the treatment of cancer. As a first-in-class antigen presenting cell (APC) activator, efti binds to MHC (major histocompatibility complex) Class II molecules on APC leading to activation and proliferation of CD8+ cytotoxic T cells, CD4+ helper T cells, dendritic cells, NK cells, and monocytes. It also upregulates the expression of key biological molecules like IFN-ƴ and CXCL10 that further boost the immune system’s ability to fight cancer. Efti is under evaluation for a variety of solid tumours including non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), and metastatic breast cancer. Its favourable safety profile enables various combinations, including with anti-PD-[L]1 immunotherapy and/or chemotherapy. Efti has received Fast Track designation in first line HNSCC and in first line NSCLC from the United States Food and Drug Administration (FDA). About ImmutepImmutep is a late-stage biotechnology company developing novel immunotherapies for cancer and autoimmune disease. The Company is a pioneer in the understanding and advancement of therapeutics related to Lymphocyte Activation Gene-3 (LAG-3), and its diversified product portfolio harnesses LAG-3’s ability to stimulate or suppress the immune response. Immutep is dedicated to leveraging its expertise to bring innovative treatment options to patients in need and to maximise value for shareholders. For more information, please visit www.immutep.com. 1. Shirish Gadgeel et al., Updated Analysis From KEYNOTE-189: Pembrolizumab or Placebo Plus Pemetrexed and Platinum for Previously Untreated Metastatic Nonsquamous Non–Small-Cell Lung Cancer. JCO 38, 1505-1517(2020). DOI:10.1200/JCO.19.03136 KEYTRUDA® is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. Australian Investors/Media:Catherine Strong, Sodali & Co.+61 (0)406 759 268; catherine.strong@sodali.com U.S. Media:Chris Basta, VP, Investor Relations and Corporate Communications+1 (631) 318 4000; chris.basta@immutep.com

免疫疗法临床结果临床3期快速通道临床1期

2025-05-06

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【第一百七十六期】AI+药物研发领域一周资讯

前言AIDD Pro 根据国内外各大网站以及人工智能药物设计主流新闻网站及公众号，从 AIDD会议、AIDD招聘，重大科研进展、行业动态、最新报告发布等角度，分析挖掘了每周人工智能辅助药物设计领域所发生的、对领域技术发展产生重大推动作用的事件，旨在帮助 AIDD领域研究人员和业内人士及时追踪最新科研动态、洞察前沿热点。如果您觉得符合以上要求的内容我们有遗漏或者更好建议，欢迎后台留言。科研进展2025年5月3日【抑制剂】J. Med. Chem. | AI驱动的新型无毒 DYRK1A 抑制剂的从头设计与开发2025年5月3日【药物递送】ACS Appl. Bio Mater. | 纳米技术辅助化疗药物递送策略：最新进展和未来展望2025年5月2日【机器学习】Chem. Res. Toxicol. | 使用化学结构进行毒性预测的机器学习：在现实世界中成功的支柱2025年5月2日【分子设计】Ind. Eng. Chem. Res. | 用于计算分子设计的不确定性感知深度强化学习方法2025年5月1日【蛋白质突变预测】J. Chem. Inf. Model. | EVOLVE：一个基于人工智能的蛋白质突变预测和进化阶段探索的Web平台2025年5月1日【PROTAC】J. Med. Chem. | PSMA引导的前列腺癌肿瘤特异性蛋白降解的PROTAC降解物具体信息，请滑动下方文字1.【抑制剂】双特异性酪氨酸磷酸化调节激酶1A （DYRK1A）与多种人类疾病有关，包括DYRK1A综合征、癌症和神经退行性疾病如阿尔茨海默病，使其成为相关的治疗靶点。在这项研究中，我们将人工智能与传统的药物发现方法相结合，设计无毒的DYRK1A抑制剂。使用集合QSAR模型预测结合亲和力，而定向信息传递神经网络评估毒性。使用基于分层图的生成模型生成新化合物，随后通过分子对接，化学合成和实验验证进行改进。这条管道导致吡唑基- 1h -吡咯[2,3-b]吡啶1被鉴定为有效的抑制剂，并由此开发了一个新的衍生物系列。酶分析证实了纳米摩尔DYRK1A的抑制作用，另外的分析显示了抗氧化和抗炎的特性。总的来说，所得到的化合物表现出强烈的DYRK1A抑制作用和良好的药理学特征。链接网址：https://pubs.acs.org/doi/10.1021/acs.jmedchem.5c00512DOI：https://doi.org/10.1021/acs.jmedchem.5c005122.【药物递送】在追求癌症治疗的过程中，纳米技术工程已经成为最简单和最有效的手段，具有在目标部位提供抗肿瘤化疗药物的潜力。利用纳米技术给药可以提供从1纳米到1000纳米不等的纳米颗粒。缩小的尺寸通过增加药物扩散和降低外排速率来提高药物的生物利用度。这些纳米载体为根据药物及其疾病的化学和生物学特性进行修饰提供了巨大的空间。此外，这些纳米制剂有助于将药物活性分子靶向到所需的位置，并且近年来变得越来越重要。它们的现代应用彻底改变了许多治疗药物的抗肿瘤作用。纳米技术具有较高的载药效率、热稳定性、易于制造、生产成本低和大规模工业化生产等特点，使纳米技术成为药物分子递送的更好平台。此外，纳米载体技术辅助药物的相互作用降低了药物的毒性和治疗剂量，降低了药物耐受性，提高了肿瘤组织中的活性药物浓度，从而降低了健康组织中的浓度。基于纳米技术的药物正在被广泛探索，并在体内和体外系统中描述了有效的癌症管理，导致许多临床试验取得了有希望的结果。本文综述了近年来不同纳米载体在肿瘤治疗中的创新作用及应用。随后，它还描述了基本的发现和方法及其对癌症治疗的影响。与常规治疗相比，纳米药物可以显著提高抗肿瘤药物的治疗效果。因此，与健康组织相关的不良影响减少，并通过增强渗透性和保留作用减少不良影响。最后，本文还讨论了纳米技术在主动治疗药物递送中的应用前景，以及纳米技术在癌症化疗药物中的应用范围。链接网址：https://pubs.acs.org/doi/10.1021/acsabm.5c00046DOI：https://doi.org/10.1021/acsabm.5c000463.【机器学习】机器学习（ML）在预测药物发现中的分子特性和毒性方面越来越有价值。然而，由于人类和动物研究需要资源，毒性相关终点在体内翻译方面的实验评估一直具有挑战性；这影响了现场的数据可用性。根据项目阶段和预测的具体目标，机器学习可以增强甚至潜在地取代传统的实验过程。例如，模型可用于选择有希望实现靶效应的化合物，或取消选择那些具有不希望的特性（例如，由于不利的药代动力学而脱靶或无效）的化合物。然而，依赖机器学习并非没有风险，因为非代表性的训练数据、不兼容的算法选择来表示底层数据，或者糟糕的模型构建和验证方法会产生偏差。这可能会导致不准确的预测，对ML预测信心的误解，最终导致次优决策。因此，了解ML模型的预测有效性对于加快药物开发时间表，同时提高决策质量至关重要。这一观点强调需要加强对机器学习模型在药物发现中的理解和应用，重点是基于小分子结构的毒性预测的定义良好的数据集。我们专注于机器学习驱动的分子特性和毒性预测成功的五个关键支柱：(1)数据集选择，(2)结构表示，(3)模型算法，(4)模型验证，以及(5)将预测转化为决策。了解这些关键支柱将促进ML研究人员和毒理学家之间的合作和协调，这将有助于推进药物发现和开发。链接网址：https://pubs.acs.org/doi/10.1021/acs.chemrestox.5c00033DOI：https://doi.org/10.1021/acs.chemrestox.5c000334.【分子设计】设计具有定制特性的分子对于开发功能优越且环境可持续的化学产品和工艺至关重要。然而，现有的计算筛选方法往往忽略了计算分子设计（CMD）中性质不确定性的关键影响，可能导致解决方案违反设计约束并在实践中表现不佳。在此，我们引入了一种新的深度强化学习（DRL）框架，DRL- cmd，它独特地集成了基于图的片段表示和属性不确定性量化，以系统地、自信地在广阔的化学空间中导航。为了评估其有效性，我们将DRL-CMD与文献报道的四种分子设计案例中的候选分子进行了比较，旨在产生具有更少分子性质不确定性的优越分子。与文献报道的分子相比，DRL-CMD大大改善了分子设计结果，平均减少了39%的约束违规和27%的不确定性边际。这种改进在具有有限数据集和极端属性范围的复杂设计案例中尤为显著。这些发现强调了DRL-CMD通过明确量化和管理不确定性来加速多尺度化学产品和工艺开发的潜力。链接网址：https://pubs.acs.org/doi/10.1021/acs.iecr.4c04993DOI：https://doi.org/10.1021/acs.iecr.4c049935.【蛋白质突变预测】虽然从序列数据中预测结构-功能关系是生物物理化学的基础，但确定蛋白质中潜在的单点和集体突变位点可以帮助我们在理解它们对蛋白质结构和功能的潜在影响方面保持领先地位。为了解决大序列空间分析的挑战，我们提出了EVOLVE，这是一个网络工具，使研究人员能够探索潜在的突变位点及其集体行为。EVOLVE集成了统计力学指导的机器学习算法来预测可能的突变位点，并结合统计力学计算突变熵来准确识别突变热点。对许多病毒蛋白序列的验证证实了其预测突变及其功能后果的能力。通过利用相变概念的统计力学，EVOLVE还量化了突变熵波动，根据世界卫生组织（WHO）的指导方针，为识别关注变量（VOC）或监测变量（VUM）提供了定量基础。EVOLVE简化了数据上传和分析，具有用户友好的界面和全面的教程。可在https://evolve-iiserkol.com免费访问EVOLVE。链接网址：https://pubs.acs.org/doi/10.1021/acs.jcim.5c00026DOI：https://doi.org/10.1021/acs.jcim.5c000266.【PROTAC】通过降解靶蛋白来治疗疾病的PROTACs是一种非常有前途的药物设计策略。然而，非疾病组织中靶蛋白的降解可能导致全身毒性。本研究利用PSMA在前列腺癌中过表达的特点，设计了PSMA引导的protacs特异性靶向前列腺癌。通过可切割连接剂将AR降解剂和BET降解剂分别与PSMA配体偶联，得到了两类PSMA引导的PROTACs。体外实验表明，psma引导的PROTACs选择性地降解过表达psma的前列腺癌细胞中的靶蛋白，而不影响其他细胞中的靶蛋白。体内研究显示，与传统的PROTACs相比，psma引导的PROTACs增强了前列腺癌组织中的药物暴露，延长了半衰期，从而获得了更强、更持久的治疗效果。这项工作为疾病组织特异性PROTAC研究提供了一条新的途径，对前列腺癌的靶向治疗具有重要意义。链接网址：https://pubs.acs.org/doi/10.1021/acs.jmedchem.5c00226DOI：https://doi.org/10.1021/acs.jmedchem.5c00226上下滚动查看更多药企动态2025年5月5日【Immutep】大涨45.6%！LAG3抗体联合K药一线治疗头颈癌较K药单药历史OS数据翻倍！达17.6个月~2025年5月5日【恒瑞医药】恒瑞医药通过港交所聆讯，H股上市进入倒计时2025年5月2日【阿斯利康】阿斯利康两项哮喘III期研究成功2025年5月2日【诺和诺德】全球首个口服版减重司美各动态具体信息，请滑动下方文字1.【Immutep】2025年5月5日——Immutep公司宣布，其TACTI-003试验的B队列中，Eftilagimod Alfa（efti）联合Pembrolizumab（商品名：KEYTRUDA®）作为一线治疗方案，在PD-L1表达水平低于1（CPS<1）的复发性/转移性头颈鳞状细胞癌（HNSCC）患者中，取得了17.6个月的成熟中位总生存期（OS）。链接网址请戳我2.【恒瑞医药】2025年5月5日，港交所官网显示，恒瑞医药已正式通过港交所聆讯，距离在港交所主板挂牌上市仅一步之遥。此次获批意义重大，据知情人士透露，恒瑞医药最快将于5月内完成上市，成为“A+H”双重上市企业，迈出国际化战略关键一步。摩根士丹利、花旗、华泰国际任联席保荐人。链接网址请戳我3.【阿斯利康】5月2日，阿斯利康宣布固定剂量三联组合疗法Breztri Aerosphere（布地奈德+福莫特罗+格隆溴铵）在III期KALOS和LOGOS研究中达到所有主要终点，与吸入性糖皮质激素/长效 β2 受体激动剂（ICS/LABA）药物相比，该三联组合疗法在改善肺功能方面具有统计学意义和临床意义。链接网址请戳我4.【诺和诺德】当地时间 5 月 2 日，诺和诺德宣布，美国 FDA 已受理每日一次、 25mg 口服版司美格鲁肽（Wegovy）的上市申请，适应症是「治疗超重或肥胖」。FDA 预计将在 2025 年第四季度做出审批决定。链接网址请戳我上下滚动查看更多会议信息2025年5月22-23日举办I-RNA 2025第五届小核酸药物产业深度聚焦峰会2025年6月12-13日智药邦举办2025人工智能与生物医药生态大会2025年6月27-28日美国华人生物医药科技协会中国分会（CBA-China）主办，苏州云程万川（盛杰）承办2025美国华人生物医药科技协会CBA-China中国年会各会议具体详情和参会方式，请滑动下方文字I-RNA 2025第五届小核酸药物产业深度聚焦峰会会议时间：2025年5月22-23日会议地点：南京会议主旨：聚焦小核酸药物的治疗潜力与技术创新，深入探讨研发难题、递送技术突破及临床转化路径，全面解读市场趋势与未来机遇，推动小核酸药物领域持续突破，共同助力行业高质量发展！链接网址请戳我2025人工智能与生物医药生态大会主办方：智药邦会议时间：2025年6月12-13日会议地点：上海会议主旨：大会将广泛邀请国内外顶尖学术界和企业界知名专家学者，共同探讨AI赋能生物医药领域的前沿进展、重要案例、关键问题和各方思考。大会旨在为各方提供一个高水平的信息沟通平台，加强交流与合作，加速生物制药相关技术和产业的发展。链接网址请戳我2025美国华人生物医药科技协会CBA-China中国年会主办方：美国华人生物医药科技协会中国分会会议时间：2025年6月27-28日会议地点：苏州会议主旨：立足国际视野及产业高度，以创新为引领，围绕全球最新监管动态、新技术/AI革新及成果转化、先进治疗技术、药物创新开发、全球药物开发策略、新兴市场出海布局等前沿热门话题，共同探索前沿技术创新与全球医药合作，促进新质生产力培育及未来产业发展，推动全球健康事业新发展。链接网址请戳我上下滚动查看更多版权信息本文内容均由小编收集于公开的各个网络平台，发布的目的仅为了方便大家一站式了解AIDD行业信息，并未对发布源头进行真实性验证。如您发现相关信息有任何版权侵扰或者信息错误，请及时联系AIDD Pro（请添加微信号18515220072）进行删改处理。原创内容未经授权，禁止转载至其他平台。有问题可发邮件至yangzhuoqi@stonewise.cn关注我，更多资讯早知道↓↓↓

蛋白降解靶向嵌合体临床1期

100 项与重组人源淋巴细胞激活基因-3（hLAG-3）融合蛋白(Immutep) 相关的药物交易

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KEGG	Wiki	ATC	Drug Bank
-	重组人源淋巴细胞激活基因-3（hLAG-3）融合蛋白(Immutep)	-	DB16150

研发状态

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适应症	最高研发状态	国家/地区	公司	日期
转移性非小细胞肺癌	临床3期	澳大利亚	Immutep SAS	2025-03-21
转移性非小细胞肺癌	临床3期	比利时	Immutep SAS	2025-03-21
转移性非小细胞肺癌	临床3期	保加利亚	Immutep SAS	2025-03-21
转移性非小细胞肺癌	临床3期	加拿大	Immutep SAS	2025-03-21
转移性非小细胞肺癌	临床3期	克罗地亚	Immutep SAS	2025-03-21
转移性非小细胞肺癌	临床3期	希腊	Immutep SAS	2025-03-21
转移性非小细胞肺癌	临床3期	印度	Immutep SAS	2025-03-21
转移性非小细胞肺癌	临床3期	爱尔兰	Immutep SAS	2025-03-21
转移性非小细胞肺癌	临床3期	意大利	Immutep SAS	2025-03-21
转移性非小细胞肺癌	临床3期	拉脱维亚	Immutep SAS	2025-03-21

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临床结果

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT06128863 (EFTISARC-NEO, GlobeNewswire) 人工标引	临床2期	软组织肉瘤新辅助	40	Eftilagimod alfa (Efti) with Radiotherapy plus KEYTRUDA® (pembrolizumab)	襯襯繭醖積鏇鏇觸觸衊(膚範範選範觸壓構鬱鏇) = 鹽淵壓網衊衊遞選獵艱範淵鹹壓鹹鹹網築鑰網 (艱鏇觸鹹製鹽艱蓋襯襯 ) 达到	积极	2025-05-27
NCT03252938 (INSIGHT-003, Company_Website) 人工标引	临床1期	非鳞状非小细胞肺癌一线	-	Eftilagimod alpha (Efti) + KEYTRUDA (Pembrolizumab) + Chemotherapy (PD-L1 TPS 0-100%)	觸蓋鏇蓋觸顧齋獵鹹積(築願鹹膚憲醖選廠簾製) = 糧膚鏇淵蓋遞齋蓋壓築觸窪製淵簾夢衊製選範 (餘襯蓋襯淵網獵顧鹹淵 ) 更多	积极	2025-05-15
				Eftilagimod alpha (Efti) + KEYTRUDA (Pembrolizumab) + Chemotherapy (PD-L1 TPS <1%)	觸蓋鏇蓋觸顧齋獵鹹積(築願鹹膚憲醖選廠簾製) = 鏇夢襯鑰範獵顧艱鏇顧觸窪製淵簾夢衊製選範 (餘襯蓋襯淵網獵顧鹹淵 ) 更多
NCT04811027 (TACTI-003 \| KEYNOTE-PNC-34 \| TACTI-003 Cohort B, GlobeNewswire) 人工标引	临床2期	头颈部鳞状细胞癌 PD-L1 CPS <1	31	Eftilagimod alfa (Efti) + Pembrolizumab (PD-L1 CPS <1)	夢膚壓艱繭築衊鹽壓夢(醖簾壓鬱壓壓築糧憲繭) = 襯廠繭醖艱夢遞網衊遞製鹹艱範選鑰網窪餘糧 (窪窪窪鹹選獵鏇積觸醖 )	积极	2025-05-05
NCT03625323 (TACTI-002 \| INSIGHT-003, CTgov)	临床2期	转移性头颈部鳞状细胞癌 \| 头颈部鳞状细胞癌 \| 非小细胞肺癌 ... 更多	187	eftilagimod alpha+pembrolizumab (KEYTRUDA®) (1st Line NSCLC)	壓網積選網鏇製製網鑰 = 鬱鹹廠鹽製簾選餘積鑰繭製膚蓋繭衊齋鑰鑰鏇 (壓範蓋夢齋醖鹹簾壓襯, 衊鬱夢觸鏇範廠衊鹽蓋 ~ 製簾築觸簾鹹獵簾齋遞) 更多	-	2024-12-18
				eftilagimod alpha+pembrolizumab (KEYTRUDA®) (2nd Line NSCLC)	壓網積選網鏇製製網鑰 = 觸獵築觸獵齋簾衊鬱範繭製膚蓋繭衊齋鑰鑰鏇 (壓範蓋夢齋醖鹹簾壓襯, 鑰襯鹽糧鏇網積窪網膚 ~ 窪鏇簾醖簾淵鑰壓憲齋) 更多
NCT04811027 (TACTI-003, ESMO_IO2024 \| GlobeNewswire) 人工标引	临床2期	头颈部鳞状细胞癌一线 PD-L1 Negative	31	Eftilagimod alpha (RECIST 1.1 + Cohort B)	糧鏇鬱願構醖膚範鹹獵(齋網鹽糧襯膚積鹹網遞) = 蓋窪憲網顧蓋襯願餘鬱獵顧艱襯蓋齋鹹壓膚齋 (鬱鑰蓋鬱遞蓋積選選觸, 19.2 ~ 54.6) 更多	积极	2024-12-16
				eftilagimod alpha (iRECIST + Cohort B)	糧鏇鬱願構醖膚範鹹獵(齋網鹽糧襯膚積鹹網遞) = 鏇鏇積鏇艱憲淵顧醖遞獵顧艱襯蓋齋鹹壓膚齋 (鬱鑰蓋鬱遞蓋積選選觸, 21.8 ~ 57.8) 更多
NCT03625323 (Pubmed \| JTO Clin Res Rep)	临床2期	转移性非小细胞肺癌二线 PD-(L)1 tumor proportion score	36	Eftilagimod alpha + Pembrolizumab	糧鹽製鏇簾範襯壓鹹製(艱鬱鏇鏇鬱餘鏇壓顧觸) = 壓衊鏇顧襯齋壓鏇淵鏇淵願簾築觸選壓廠艱糧 (鏇製觸鑰壓淵襯憲糧糧 ) 更多	积极	2024-11-01
NCT04811027 (TACTI-003, ESMO2024) 人工标引	临床2期	头颈部肿瘤一线 PD-L1 Expression (CPS >= 1)	118	Eftilagimod Alpha + pembrolizumab	憲鑰糧顧簾壓醖鹽積繭(鏇襯齋蓋顧觸遞蓋膚餘) = 鹽艱顧構鹽製鹽醖顧襯鹹襯鬱膚選窪艱衊衊鑰 (獵製選窪鬱觸糧齋餘齋 ) 更多	积极	2024-09-15
				Pembrolizumab	憲鑰糧顧簾壓醖鹽積繭(鏇襯齋蓋顧觸遞蓋膚餘) = 艱襯艱選蓋膚範膚醖襯鹹襯鬱膚選窪艱衊衊鑰 (獵製選窪鬱觸糧齋餘齋 ) 更多
NCT04811027 (TACTI-003, Company_Website) 人工标引	临床2期	头颈部鳞状细胞癌一线	138	Eftilagimod alfa (Efti) + KEYTRUDA (PD-L1 Expression (CPS >20))	壓餘壓襯鏇構廠鹹顧膚(鏇鏇製憲獵鹽範糧膚鬱) = 艱壓鑰窪鑰選糧窪襯糧鬱衊衊餘壓壓願蓋觸鹽 (願顧遞鹽憲襯鑰衊淵鬱 ) 更多	积极	2024-06-27
				Eftilagimod alfa (Efti) + KEYTRUDA (PD-L1 Expression (CPS 1-19))	壓餘壓襯鏇構廠鹹顧膚(鏇鏇製憲獵鹽範糧膚鬱) = 顧鹽鹹齋鹽醖糧鹹衊襯鬱衊衊餘壓壓願蓋觸鹽 (願顧遞鹽憲襯鑰衊淵鬱 )
NCT05747794 (AIPAC-003, ESMO_BC 12024 \| ESMO_BC 22024) 人工标引	临床2/3期	转移性乳腺癌 HER2 Negative \| Hormone Receptor Positive	6	eftilagimod alpha+paclitaxel	網遞艱淵築醖襯願範鏇(壓製鑰艱願糧淵鑰積簾) = none 顧餘夢糧鏇鹹蓋醖積願 (鏇網獵鏇艱淵廠廠製構 ) 更多	积极	2024-05-16
NCT05747794 (AIPAC-003, Biospace) 人工标引	临床2/3期	转移性乳腺癌	6	Eftilagimod alpha 90 mg s.c.	積觸遞壓壓網壓壓夢衊(願網簾窪醖鹽製構繭獵) = None 顧窪獵襯蓋鬱窪襯遞醖 (觸淵憲膚鹹餘鹹鏇壓觸 ) 更多	积极	2024-05-15