A Randomised, Double-blind, Placebo-controlled Phase I Study of the Safety and Tolerability, Pharmacokinetics, and Pharmacodynamics of a Single Intravenous Dose of GSK2831781 in Healthy Japanese and Caucasian Participants, and a Single Subcutaneous Dose of GSK2831781 in Healthy Caucasian Participants

This is a double-blind, placebo-controlled, randomized, parallel group, two-part study where single IV doses of GSK2831781 will be administered to healthy Japanese and Caucasian subjects in part A and SC doses will be administered to healthy Caucasian subjects in part B. GSK2831781 is a humanized, antibody-dependent cell cytotoxicity (ADCC) enhanced depleting monoclonal antibody that is specific to the lymphocyte activation gene-3 (LAG3) protein. LAG3 is a transmembrane receptor, which is upregulated on T cells following activation. The objective of the study is to assess the safety, tolerability, PK, PD and immunogenicity post administration of GSK2831781 in healthy subjects. The duration of the study is approximately 147 days for each subject enrolled. Approximately 36 subjects will be enrolled in the study, 16 subjects in Part A and 20 subjects in Part B.

开始日期2019-06-10

申办/合作机构

GSK Plc

NCT03893565

/ Terminated临床2期

A Multicentre Randomized, Double-blind, Placebo-controlled Phase 2 Study to Evaluate the Safety, Tolerability, Efficacy, Dose-response, Pharmacokinetics and Pharmacodynamics of Repeat Dosing of an Anti-LAG3 Cell Depleting Monoclonal Antibody (GSK2831781) in Patients With Active Ulcerative Colitis

This is a Phase 2, multicenter, randomized, double-blind, parallel group, placebo-controlled study to investigate the safety, tolerability, efficacy and dose-response of GSK2831781 in participants with moderate to severe active ulcerative colitis. The study consists of a 5-week screening window, 10-week Induction Phase, 30-week double-blind Extended Treatment Phase (ETP) with 42-week Follow-Up Phase. Non-Responders identified following the Week 10 assessment will be allocated to open label treatment, consisting of Induction (Weeks 12 to 22), an Open label ETP (Weeks 22 to 42) and a follow-Up to Week 54.

开始日期2019-05-06

申办/合作机构

GSK Plc

NCT02195349

/ Completed临床1期

A Randomised, Double Blind (Sponsor Unblinded), Placebo-controlled, Single Ascending Dose Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of a IV Dose of GSK2831781 in Healthy Volunteers and Patients With Plaque Psoriasis

This study is a phase I, randomised, double blind (sponsor unblinded), placebo-controlled, single ascending dose study GSK2831781 administered by IV. GSK2831781 is a humanized Antibody Dependent Cell Cytotoxicity (ADCC) enhanced monoclonal afucosylated antibody that is specific to the Lymphocyte Activation Gene-3 (LAG-3) protein. This is the first administration of GSK2831781 in humans and will evaluate in two parts the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and immunogenicity of single IV doses of GSK2831781 administered to healthy subjects previously vaccinated with Bacillus Calmette Guérin (BCG) (Part A delayed type hypersensitivity [DTH] cohorts) and patients with plaque psoriasis (Part B). The inclusion of DTH and psoriasis subjects to explore the mechanism in biopsies and clinical response endpoints in these populations, as well as investigate systemic biomarkers will provide useful information prior to conducting studies in other immune-inflammatory disease which will involve more invasive tissue biopsies. Measuring the pharmacology of GSK2831781 using the depletion of LAG-3+ T-cells in skin biopsies from Tuberculin Purified Protein Derivative (PPD) skin challenge and lesional skin biopsies from patients with psoriasis, will be helpful in understanding of the dose response relationship, which will be important for designing future studies in immuno-inflammatory diseases, including psoriasis. Approximately 67 subjects will be enrolled to complete dosing and critical assessments. The subject numbers will be split to approximately 40 healthy subjects (Part A) and 27 patients with psoriasis (Part B).

开始日期2014-07-30

申办/合作机构

GSK Plc

[+1]

100 项与 GSK-2831781 相关的临床结果

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100 项与 GSK-2831781 相关的转化医学

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100 项与 GSK-2831781 相关的专利（医药）

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项与 GSK-2831781 相关的文献（医药）

2023-08-01·Alimentary pharmacology & therapeutics

A randomised, double‐blind, placebo‐controlled study of the LAG‐3‐depleting monoclonal antibody GSK2831781 in patients with active ulcerative colitis

Article

作者: Peyrin‐Biroulet, Laurent ; Prasad, Naveen ; Srinivasan, Naren ; Bouma, Gerben ; Tarzi, Ruth ; Liefaard, Lia ; Sandborn, William J. ; Cameron, Raymond ; D'Haens, Geert ; Kayali, Zeid ; Hanauer, Stephen ; Beaton, Andrew ; Lisi, Edoardo ; Marks, Daniel J. B.

Summary:

Background:

Selective depletion of T cells expressing LAG‐3, an immune checkpoint receptor that is upregulated on activated T cells, has been investigated in pre‐clinical models as a potential therapeutic approach in inflammatory and autoimmune diseases where activated T cells are implicated.

Aims:

GSK2831781, a depleting monoclonal antibody that specifically binds LAG‐3 proteins, may deplete activated LAG‐3+ cells in ulcerative colitis (UC).

Methods:

Patients with moderate to severe UC were randomised to GSK2831781 or placebo. Safety, tolerability, efficacy, pharmacokinetics and pharmacodynamics of GSK2831781 were evaluated.

Results:

One hundred four participants across all dose levels were randomised prior to an interim analysis indicating efficacy futility criteria had been met. Efficacy results focus on the double‐blind induction phase of the study (GSK2831781 450 mg intravenously [IV], N = 48; placebo, N = 27). Median change from baseline (95% credible interval [CrI]) in complete Mayo score was similar between groups (GSK2831781 450 mg IV: −1.4 [−2.2, −0.7]; placebo: −1.4 [−2.4, −0.5]). Response rates for endoscopic improvement favoured placebo. Clinical remission rates were similar between groups. In the 450‐mg IV group, 14 (29%) participants had an adverse event of UC versus 1 (4%) with placebo. LAG‐3+ cells were depleted to 51% of baseline in blood; however, there was no reduction in LAG‐3+ cells in the colonic mucosa. Transcriptomic analysis of colon biopsies showed no difference between groups.

Conclusion:

Despite evidence of target cell depletion in blood, GSK2831781 failed to reduce inflammation in the colonic mucosa suggesting no pharmacological effect. The study was terminated early (NCT03893565).

2022-11-01·Clinical pharmacology in drug development

Randomized Trial of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of GSK2831781 in Healthy Japanese and White Participants

Article

作者: Srinivasan, Naren ; Lisi, Edoardo ; Panoilia, Eirini ; van den Berg, Frans ; Tarzi, Ruth ; Marks, Daniel J.B. ; Bouma, Gerben ; Cui, Yi ; Hajduk, Eva ; Liefaard, Lia ; Gross, Annette S.

Abstract:

This study investigated ethnic differences in the safety, tolerability, pharmacokinetics, and pharmacodynamics of GSK2831781, an anti–lymphocyte activation gene 3 (LAG3) monoclonal antibody, in healthy participants, and determined local tolerability and bioavailability following subcutaneous (SC) administration. A double‐blind, randomized study of (A) single intravenous (IV) doses of GSK2831781 450 mg or placebo in Japanese and White participants; and (B) single SC doses of GSK2831781 150 or 450 mg, or placebo in White participants, was conducted. Blood samples for analyses were collected before dosing and over 112 days after dosing. GSK2831781 was well tolerated in Japanese and White participants after both IV and SC doses, with the adverse event profile in Japanese being consistent with other populations. There were no injection site adverse events. There was no evidence of differences in systemic exposure among Japanese and White participants. Systemic exposure did not vary with body weight. SC bioavailability was 76.5%, as estimated using population pharmacokinetic modeling. Full and sustained target engagement and evidence of LAG3+ cell depletion (≈53%–66%) were observed in both populations and after both administration routes. No evidence of reduced circulating regulatory T cells (CD4+CD25+CD127lowFoxP3+) was observed. Following IV and SC administration, GSK2831781 depleted circulating LAG3+ T cells with no interethnic difference observed. There were no major impacts on circulating regulatory T cells.

2021-05-01·Clinical pharmacology and therapeutics

Depletion of LAG‐3⁺ T Cells Translated to Pharmacology and Improvement in Psoriasis Disease Activity: A Phase I Randomized Study of mAb GSK2831781

Article

作者: Schmidt, Tim S. ; Wisniacki, Nicolas ; Hughes, Stephen A. ; Leavens, Karen ; Edwards, Ken ; Richards, Anna ; J.B. Marks, Daniel ; Albayaty, Muna ; Savage, Caroline O.S. ; Fuhr, Rainard ; Tarzi, Ruth M. ; Delves, Christopher J. ; Nevin, Katherine L. ; Brett, Sara J. ; Fortunato, Léa ; Cui, Yi ; Stone, John ; Hopkins, Thomas G. ; Anselm, Rabia ; Webb, Thomas M. ; Barrett, Christine ; Ellis, Joanne ; Charles, Emilie ; Liefaard, Lia ; Feeney, Maria ; Srinivasan, Naren ; Tang, Shuo ; Coenen, Martin

Activated T cells drive a range of immune‐mediated inflammatory diseases. LAG‐3 is transiently expressed on recently activated CD4+ and CD8+ T cells. We describe the engineering and first‐in‐human clinical study (NCT02195349) of GSK2831781 (an afucosylated humanized IgG1 monoclonal antibody enhanced with high affinity for Fc receptors and LAG‐3 and antibody‐dependent cellular cytotoxicity capabilities), which depletes LAG‐3 expressing cells. GSK2831781 was tested in a phase I/Ib, double‐blind, placebo‐controlled clinical study, which randomized 40 healthy participants (part A) and 27 patients with psoriasis (part B) to single doses of GSK2831781 (up to 0.15 and 5 mg/kg, respectively) or placebo. Adverse events were generally balanced across groups, with no safety or tolerability concern identified. LAG‐3+ cell depletion in peripheral blood was observed at doses ≥ 0.15 mg/kg and was dose‐dependent. In biopsies of psoriasis plaques, a reduction in mean group LAG‐3+ and CD3+ T‐cell counts was observed following treatment. Downregulation of proinflammatory genes (IL‐17A, IL‐17F, IFNγ, and S100A12) and upregulation of the epithelial barrier integrity gene, CDHR1, was observed with the 5 mg/kg dose of GSK2831781. Psoriasis disease activity improved up to day 43 at all GSK2831781 doses (0.5, 1.5, and 5 mg/kg) compared with placebo. Depletion of LAG‐3‐expressing activated T cells is a novel approach, and this first clinical study shows that GSK2831781 is pharmacologically active and provides encouraging early evidence of clinical effects in psoriasis, which warrants further investigation in T‐cell‐mediated inflammatory diseases.

项与 GSK-2831781 相关的新闻（医药）

2025-12-11

·生物制药小编

下一个要申报LAG-3

近日，Dr. Reddy’s Laboratories与Immutep达成合作协议，共同开发和商业化Immutep的 LAG-3 融合蛋白Eftilagimod Alfa（Efti）。据协议，Dr. Reddy’s将获得efti除北美、欧洲、日本和大中华区以外所有国家开发和商业化的独家权利，Immutep仍保有在全球范围内对efti的生产权利。为此，Immutep将获得Dr. Reddy’s支付的2000万美元预付款，以及有资格获得3.495亿美元的监管和商业里程碑付款，以及两位数的销售分成。下一个申报LAG-3吗？ Efti（IMP321）是一种可溶性二聚体重组蛋白，是首个进入临床试验的LAG-3融合蛋白，Efti可以与MHC class II 结合，介导APC活化。更早之前（2013年），该公司已将Efti在大中华区的开发和商业化权利授权给了亿腾医药。围绕Efti，Immutep开发了非小细胞肺癌、头颈癌、乳腺癌、软组织肉瘤等多个适应症。对于头颈癌，公司已经有上市计划。今年5月，公布的针对复发或转移性头颈部鳞状细胞癌（PD-L1 CPS<1）一线治疗的Ⅱb期临床TACTI-003显示，Efti+Keytruda在这一患者群体中取得了17.6个月中位总生存期，显著优于历史数据（已批准药物），公司已计划与FDA讨论针对该适应症的监管路径。目前，Efti针对非小细胞肺癌已经进入了Ⅲ期（TACTI-004）阶段，与Keytruda+化疗联用，作为晚期或转移性非小细胞肺癌的一线治疗方案，其疗效数据预计将在2026年第一季度公布。 LAG-3布局管线最多的公司 Immutep可以说是LAG-3 靶点“管线布局最多的公司，既开发了LAG-3的阻断剂，也开发了激动剂，适应症覆盖了肿瘤以及自身免疫病。包括Efti在内，Immutep曾经开发了四条LAG-3管线：IMP761、IMP701、IMP731。 IMP761是一种针对自身免疫病的LAG-3激动剂抗体，是除了Efti外，Immutep唯一还在自主推进的LAG-3管线。IMP761 IMP761主要是通过靶向活化T细胞表面LAG-3受体，促使更强的抑制信号传递到T细胞，进而阻止其继续在患者自身组织中增殖以及反应。目前，IMP761处于临床Ⅰ期阶段。今年6月，Immutep公布的Ⅰ期临床显示，最高剂量（0.9 mg/kg）组中，IMP761的安全性和耐受性良好，未出现治疗相关不良反应，10天的T细胞浸润抑制达80%。目前，公司正推进其剂量递增试验，更多数据预计2025年年底前公布。 MP701是一种针对肿瘤的LAG-3阻断性抗体，旨在用以阻断肿瘤浸润T细胞中LAG-3介导的抑制信号，以使CD8 T细胞更好的产生针对肿瘤细胞的细胞毒性反应。2012年，Immutep将其独家授权给了CoStim公司（CoStim2014年被诺华收购），现在由诺华全权负责其临床开发，目前已进展到临床II期。 IMP731也是一种LAG-3阻断性抗体，但是针对针对自身免疫性病，旨在杀死少量浸入自身免疫疾病部位的LAG-3活化的T细胞。2010年，Immutep将其全球独家权益授权给了GSK。不过这个项目在GSK手中进展并不顺利，近两年再未出现临床试验更新，且已经不在Immutep的管线当中了，基本处于搁置状态。总结 LAG-3是继CTLA-4、PD-1/L1后，第三个获批使用的免疫检查点抑制剂，目前唯一获批LAG-3靶向药仍是来自百时美施贵宝的Opdualag（LAG-3+PD-1联用组合）。 Eftilagimod是继Opdualag之外少有在临床中取得积极数据的LAG-3候选管线，如果能在黑色素瘤外的其他实体瘤中取得III期阳性结果，将进一步验证LAG-3作为PD-1强搭档的临床价值。参考出处： https://www.fiercebiotech.com/biotech/dr-reddys-pens-370m-pact-rights-immuteps-phase-3-stage-immunotherapy-certain-markets https://www.globenewswire.com/news-release/2025/12/08/3201497/0/en/Immutep-and-Dr-Reddy-s-enters-into-Strategic-Collaboration-for-Commercialisation-of-an-Innovative-Oncology-Drug-Eftilagimod-Alfa.html https://www.immutep.com/immutep-quarterly-activities-report-q4-fy25/

临床2期引进/卖出并购临床3期临床1期

2024-04-29

·GlobeNewswire-Health Care

Immutep Quarterly Activities Report Q3 FY24

Media Release First clinical data from the safety lead-in of AIPAC-003 in metastatic breast cancer shows 90mg dosing of efti safe and well tolerated: 50% overall response rate, including one patient reporting a complete response (complete disappearance of all lesions), and a 100% disease control rateSubsequent to quarter end announced a positive preliminary response rate of 26.9% in first line metastatic head and neck squamous cell carcinoma patients with negative PD-L1 expressionPreclinical studies of IMP761 progressing to clinical trials mid-CY2024Anne Anderson joins as independent non-executive director on Immutep’s Board SYDNEY, AUSTRALIA, April 29, 2024 (GLOBE NEWSWIRE) -- Immutep Limited (ASX: IMM; NASDAQ: IMMP) ("Immutep” or “the Company”), a clinical-stage biotechnology company developing novel LAG-3 immunotherapies for cancer and autoimmune disease, provides an update on the ongoing development of its product candidates, eftilagimod alpha (efti) and IMP761 for the quarter ended 31 March 2024 (Q3 FY24). EFTI DEVELOPMENT PROGRAM FOR CANCER TACTI-002 (KEYNOTE-PN798) – Phase II clinical trial in 1L NSCLCThe TACTI-002 trial is ongoing with Immutep continuing to follow patients with 1L NSCLC (Part A) where, encouragingly, a median Overall Survival has not yet been reached in patients with high PD-L1 expression (TPS ≥50%). As previously reported at ESMO 2023, excellent median Overall Survival rates were seen across all levels of PD-L1 expression, including in patients expressing any PD-L1 (patients with a Tumor Proportion Score [TPS] of >1%) and patients with low PD-L1 expression (TPS 1-49%), with 35.5 months and 23.4 months reported respectively. Immutep has previously reported final data from Parts B and C of the TACTI-002 trial. TACTI-003 (KEYNOTE-PNC34) – Phase IIb clinical trial in 1L HNSCCThe TACTI-003 multicenter Phase IIb trial evaluating efti in combination with MSD’s anti-PD-1 therapy KEYTRUDA® (pembrolizumab) is ongoing with a total of 171 first line head and neck squamous cell carcinoma (1L HNSCC) patients enrolled. Cohort A evaluating efti in combination with KEYTRUDA® as compared to KEYTRUDA® monotherapy (randomised) involves 138 patients with PD-L1 positive (Combined Positive Score [CPS] ≥1) tumours and Cohort B (non-randomised) includes 33 patients with PD-L1 negative tumours. Subsequent to quarter end Immutep announced positive preliminary topline results from Cohort B. The investigational immuno-oncology combination demonstrates an overall response rate (ORR) of 26.9% and disease control rate (DCR) of 57.7% in 26 evaluable patients whose tumours do not express PD-L1 (CPS<1), according to RECIST 1.1, which compares favourably to historical controls. The final number of evaluable patients in Cohort B is expected to be higher and additional data, including complete response rate, is expected to be released together with Cohort A data. Data collection, cleaning, and analysis continue for TACTI-003, and the Company expects to report the primary endpoint (overall response rate according to RECIST1.1) from Cohorts A & B in H1 CY2024. TACTI-004 – Phase III registrational trial in 1L NSCLCImmutep continued to advance the necessary preparations for the Phase III TACTI-004 trial in first line non-small cell lung cancer (1L NSCLC) during the quarter. Productive interactions with regulatory agencies as well as with other stakeholders and potential partners are ongoing. Immutep expects to announce the trial design for TACTI-004 in H1 CY2024. AIPAC-003 – Integrated Phase II/III trial in MBCImmutep announced the first clinical data from the 90mg dosing of efti, the highest dose ever administered to patients, from patients participating in the safety lead-in of the AIPAC-003 trial in metastatic breast cancer (MBC). Data from the six patients in the safety lead-in showed the 90mg dose of efti in combination with paclitaxel is safe and well tolerated. The initial efficacy data was also encouraging, with a 50% overall response rate, including one patient reporting a complete response (complete disappearance of all lesions), and a 100% disease control rate. The trial has proceeded to the randomised Phase II portion of study consisting of up to 58 evaluable patients who will receive 30mg efti or 90mg efti to determine the optimal biological dose of efti in combination with paclitaxel. Currently, 34 patients have been dosed in the randomised part. Further updates from AIPAC-003 will be provided in CY2024. INSIGHT-003 – Phase I in non-squamous 1L NSCLCThe investigator-initiated INSIGHT-003 trial continued to enrol patients throughout the quarter, with 38 out of a total of 50 patients enrolled and safely dosed across six sites in Germany. INSIGHT-003 evaluates a triple combination therapy consisting of efti and an approved standard of care combination of chemotherapy (carboplatin and pemetrexed) and anti-PD-1 therapy (pembrolizumab) in patients as first line treatment in non-squamous NSCLC adenocarcinomas. INSIGHT-005 – Phase I trial in Urothelial CarcinomaThe first patient in the investigator-initiated INSIGHT-005 trial was enrolled and safely dosed, as announced in January 2024. The study is evaluating efti and the anti-PD-L1 therapy BAVENCIO® (avelumab) in up to 30 patients with metastatic urothelial cancer and is jointly funded with Merck KGaA, Darmstadt, Germany. EFTISARC-NEO – Phase II Trial in Soft Tissue SarcomaThe investigator-initiated EFTISARC-NEO trial is ongoing with 14 patients now enrolled and safely dosed. The study evaluates efti in combination with pembrolizumab and radiotherapy in up to 40 soft tissue sarcoma (STS) patients in the neoadjuvant (prior to surgery) setting. IMP761 DEVELOPMENT PROGRAM FOR AUTOIMMUNE DISEASEIMP761 is the Company’s proprietary preclinical candidate and world’s first LAG-3 agonist that aims to treat the underlying cause of multiple autoimmune diseases. Throughout the quarter, Immutep progressed its pre-clinical development and IND-enabling toxicology studies for IMP761 to evaluate the safety and toxicity of its product candidate before entering first-in-human trials. Subsequent to quarter end, Immutep entered into an agreement with the Centre for Human Drug Research (CHDR), a world-class institute in Leiden, the Netherlands specializing in cutting-edge early-stage clinical drug research, to perform a first-in-human clinical study of IMP761, which it expects to begin mid-CY2024. GLAXOSMITHKLINE (GSK) - IMP731 (GSK2831781) As detailed in Immutep’s half year report in February 2024, Immutep received from GSK a written notice of termination of its exclusive License and Research Collaboration Agreement with GSK entered into in 2010 for the development of GSK2831781, a LAG-3 depleting antibody derived from Immutep’s IMP731 antibody, targeting autoimmune disease, with an effective termination date of 30 May 2024. The Company expects no material impact on the financial statements due to the termination. CORPORATE & FINANCIAL SUMMARY Board AppointmentIn February 2024, Anne Anderson was appointed as an independent non-executive director of Immutep Limited. Ms Anderson has extensive board and leadership experience serving Australian and international companies and brings considerable capability across capital markets, risk management and governance to Immutep’s Board. Cash Flow SummaryDuring the quarter, Immutep continued to fund the advancement of its clinical trial programs for efti and preclinical program for IMP761 to create value for shareholders. The Company is well funded with a strong cash and cash equivalent balance as at 31 March 2024 of approximately $95.4 million, giving it an expected cash reach into early CY2026. Cash receipts from customers in Q3 FY24 were $14k, compared to $38k in Q2 FY24. The net cash used in G&A activities in the quarter was $0.7 million, compared to $0.8 million in Q2 FY24. Payments of $310k to Related Parties comprises Non-Executive Directors’ fees and Executive Directors’ remuneration. The net cash used in R&D activities in the quarter was $6.9 million, which is consistent with Q2 FY24. Payment for staff costs was $2.0 million in the quarter compared to $2.2 million last quarter. Total net cash outflows used in operating activities in the quarter was $9.0 million compared to $5.5 million in Q2 FY24. This difference was mainly due to the receipt of $3.8 million in R&D tax grants in Q2 FY24. About ImmutepImmutep is a clinical stage biotechnology company developing novel LAG-3 immunotherapy for cancer and autoimmune disease. We are pioneers in the understanding and advancement of therapeutics related to Lymphocyte Activation Gene-3 (LAG-3), and our diversified product portfolio harnesses its unique 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. Australian Investors/Media:Catherine Strong, Citadel-MAGNUS+61 (0)406 759 268; cstrong@citadelmagnus.com U.S. Investors/Media:Chris Basta, VP, Investor Relations and Corporate Communications+1 (631) 318 4000; chris.basta@immutep.com

临床2期临床结果引进/卖出临床1期临床3期

2023-05-18

·佰傲谷BioValley

LAG-3+PD-1取得OS突破，Immutep股价大涨65%

2023年5月17日，Immutep公布了其LAG-3融合蛋白Eftilagimod联合PD-1用于非小细胞肺癌一线治疗的Ⅱ期临床TACTI-002数据，结果显示，Eftilagimod+PD-1在NSCLC患者中取得出色的初步OS，其在PD-L1>1%NSCLC患者中的初步总生存OS为25个月，这已超以往PD-1单药以及联合治疗的OS数据。在PD-L1>1%的NSCLC患者中，既往PD-1单药治疗的中位OS为16.4个月，PD-1联合化疗的中位OS为15.8- 23.3个月，PD-1联合CTLA -4的中位OS为17.1个月。Eftilagimod+PD-1有望为NSCLC患者带来长期的生存获益。受此积极消息影响，Immutep昨日股价大涨65%。IMP321（Prima BioMed/Immutep）一种可溶性二聚体重组蛋白，是首个进入临床试验的LAG-3 融合蛋白，可以与MHC class II 结合，介导APC活化。此前，该公司已将IMP321在华开发和商业化特许权授予给亿腾医药。Immutep对Eftilagimod alpha的联合方案做了很多尝试，包括与化疗药物、免疫抑制剂药物，以及作为癌症疫苗的佐剂使用。Immutep是最重视LAG-3企业之一，除了Eftilagimod之外，公司还有三条LAG-3管线在研IMP761、IMP701，IMP731，覆盖了肿瘤以及自身免疫病。其中IMP731（GSK-2831781）是一种针对自身免疫性病的LAG-3单抗，2010年被GSK以1亿美元的首付款和里程碑付款引进全球独家授权。不过这个项目在GSK手中进展并不顺利，2020年1月23日，GSK宣布停止一项IMP731在溃疡性结肠炎中的Ⅱ期临床试验，在独立数据监测委员会对该试验进行中期评估后。MP701为用于肿瘤治疗的LAG-3阻断性抗体，已被授权给诺华开发，目前已进展到临床IIa期。IMP761是用于自身免疫性病的LAG-3激动剂抗体（人源化IgG4单克隆抗体），目前还处于临床前阶段。总结LAG-3是继CTLA-4、PD-1/L1后，第三个获批使用的免疫检查点抑制剂。去年3月首个LAG-3+PD-1联用组合Opdualag获得FDA批准上市，验证了LAG-3与PD-1/L-1的协同价值，Eftilagimod是继BMS的relatlimab-rmbw之外少有在临床中取得积极数据的LAG-3候选产品。参考出处：https://www.immutep.com/detail/immutep-s-efti-in-combination-with-pembrolizumab-achieves-excellent-initial-overall-survival-benefit-in-1st-line-non-small-cell-lung-cancer.htmlImmutep股价大涨65%：LAG-3+PD-1一线NSCLC获积极OS数据/医药笔记近期热门视频更多精彩视频，尽在佰傲谷视频号，欢迎关注~本周好文推荐如需转载请联系佰傲谷并在醒目位置注明出处﹀点亮在看，传递信息♥

临床2期引进/卖出疫苗临床1期临床终止

100 项与 GSK-2831781 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	GSK-2831781	-	-

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
活动性重度溃疡性结肠炎	临床2期	美国	GSK Plc	2019-05-06
活动性重度溃疡性结肠炎	临床2期	日本	GSK Plc	2019-05-06
活动性重度溃疡性结肠炎	临床2期	保加利亚	GSK Plc	2019-05-06
活动性重度溃疡性结肠炎	临床2期	捷克	GSK Plc	2019-05-06
活动性重度溃疡性结肠炎	临床2期	爱沙尼亚	GSK Plc	2019-05-06
活动性重度溃疡性结肠炎	临床2期	法国	GSK Plc	2019-05-06
活动性重度溃疡性结肠炎	临床2期	印度	GSK Plc	2019-05-06
活动性重度溃疡性结肠炎	临床2期	荷兰	GSK Plc	2019-05-06
活动性重度溃疡性结肠炎	临床2期	波兰	GSK Plc	2019-05-06
活动性重度溃疡性结肠炎	临床2期	俄罗斯	GSK Plc	2019-05-06

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临床结果

适应症

分期

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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


NCT03965533 (Pubmed) 人工标引	临床1期	-	-	GSK 2831781	網鹹膚醖襯築顧獵艱餘(鹹襯衊醖憲窪淵襯壓餘) = GSK2831781 was well tolerated in Japanese and White participants after both IV and SC doses, with the adverse event profile in Japanese being consistent with other populations 網願積蓋憲構膚選憲選 (艱艱壓窪衊艱鹹淵餘夢 )	积极	2022-09-11
				Placebo
NCT03893565 (CTgov)	临床2期	活动性重度溃疡性结肠炎	104	Placebo (Placebo IV)	觸鹽夢廠廠膚簾網繭蓋 = 獵範壓積襯遞鏇構憲淵淵夢齋網壓膚鬱憲觸鹹 (廠觸觸醖糧襯餘廠鏇鑰, 顧糧窪範遞餘積壓糧鏇 ~ 獵襯範製構觸廠製網顧) 更多	-	2022-04-27
				GSK2831781 (GSK2831781 450 mg IV)	觸鹽夢廠廠膚簾網繭蓋 = 廠鏇膚廠齋醖製簾鏇齋淵夢齋網壓膚鬱憲觸鹹 (廠觸觸醖糧襯餘廠鏇鑰, 齋鬱齋醖淵範艱艱鑰網 ~ 衊壓觸鏇糧築繭窪鬱築) 更多
NCT03965533 (CTgov)	临床1期	-	36	Placebo (Part A: Placebo IV- Caucasian Participants)	簾繭獵艱衊鹹製壓糧選 = 構淵築積繭鏇膚顧範艱醖淵鹹構鏇積艱鏇襯鹽 (淵夢築淵繭製範膚壓範, 遞鬱衊廠築憲簾願網夢 ~ 窪蓋顧醖網膚網艱鹽鏇) 更多	-	2020-11-18
				GSK2831781 (Part A: GSK2831781 450 mg IV- Caucasian Participants)	簾繭獵艱衊鹹製壓糧選 = 廠廠廠窪蓋獵醖壓窪齋醖淵鹹構鏇積艱鏇襯鹽 (淵夢築淵繭製範膚壓範, 構鹽繭鹽鬱鏇襯觸窪鏇 ~ 糧襯糧構糧築憲製窪窪) 更多