Expert opinion on investigational drugs最新文献_第9页

Immune checkpoint modulators in early clinical development for the treatment of type 1 diabetes 用于治疗 1 型糖尿病的早期临床开发免疫检查点调节剂

IF 6.1 2区医学

Expert opinion on investigational drugs Pub Date : 2024-03-01 DOI: 10.1080/13543784.2024.2326036

Ernesto Maddaloni, Rocco Amendolara, Angela Balena, Alessandro Latino, Rosario Luigi Sessa, Raffaella Buzzetti

引用次数: 0

Enhancing anti-CD274 (PD-L1) targeting through combinatorial immunotherapy with bispecific antibodies and fusion proteins: from preclinical to phase II clinical trials. 通过双特异性抗体和融合蛋白的组合免疫疗法增强抗CD274（PD-L1）靶向性：从临床前到II期临床试验。

IF 6.1 2区医学

Expert opinion on investigational drugs Pub Date : 2024-03-01 Epub Date: 2024-02-23 DOI: 10.1080/13543784.2024.2319317

Dominik Kiem, Matthias Ocker, Richard Greil, Daniel Neureiter, Thomas Melchardt

{"title":"Enhancing anti-CD274 (PD-L1) targeting through combinatorial immunotherapy with bispecific antibodies and fusion proteins: from preclinical to phase II clinical trials.","authors":"Dominik Kiem, Matthias Ocker, Richard Greil, Daniel Neureiter, Thomas Melchardt","doi":"10.1080/13543784.2024.2319317","DOIUrl":"10.1080/13543784.2024.2319317","url":null,"abstract":"Introduction: Immune checkpoint inhibitors have achieved great success in the treatment of many different types of cancer. Programmed cell death protein ligand 1 (PD-L1, CD274) is a major immunosuppressive immune checkpoint and a target for several already approved monoclonal antibodies. Despite this, novel strategies are under development, as the overall response remains low.Areas covered: In this review, an overview of the current biomarkers for response to PD-L1 inhibitor treatment is given, followed by a discussion of potential novel biomarkers, including tumor mutational burden and circulating tumor DNA. Combinatorial immunotherapy is a potential novel strategy to increase the response to PD-L1 inhibitor treatment and currently, several interesting bispecific antibodies as well as bispecific fusion proteins are undergoing early clinical investigation. We focus on substances targeting PD-L1 and a secondary target, and a secondary immunomodulatory target like CTLA-4, TIGIT, or CD47.Expert opinion: Overall, the presented studies show anti-tumor activity of these combinatorial immunotherapeutic approaches. However, still relatively low response rates suggest a need for better biomarkers.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139729419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Investigational pharmacological agents for the treatment of ARDS. 用于治疗 ARDS 的试验性药物。

IF 6.1 2区医学

Expert opinion on investigational drugs Pub Date : 2024-03-01 Epub Date: 2024-02-27 DOI: 10.1080/13543784.2024.2315128

Katyayini Aribindi, Michelle Lim, Satyan Lakshminrusimha, Timothy Albertson

{"title":"Investigational pharmacological agents for the treatment of ARDS.","authors":"Katyayini Aribindi, Michelle Lim, Satyan Lakshminrusimha, Timothy Albertson","doi":"10.1080/13543784.2024.2315128","DOIUrl":"10.1080/13543784.2024.2315128","url":null,"abstract":"Introduction: Acute Respiratory Distress Syndrome (ARDS) is a heterogeneous form of lung injury with severe hypoxemia and bilateral infiltrates after an inciting event that results in diffuse lung inflammation with a high mortality rate. While research in COVID-related ARDS has resulted in several pharmacotherapeutic agents that have undergone successful investigation, non-COVID ARDS studies have not resulted in many widely accepted pharmacotherapeutic agents despite exhaustive research.Areas covered: The aim of this review is to discuss adjuvant pharmacotherapies targeting non-COVID Acute Lung Injury (ALI)/ARDS and novel therapeutics in COVID associated ALI/ARDS. In ARDS, variable data may support selective use of neuromuscular blocking agents, corticosteroids and neutrophil elastase inhibitors, but are not yet universally used. COVID-ALI/ARDS has data supporting the use of IL-6 monoclonal antibodies, corticosteroids, and JAK inhibitor therapy.Expert opinion: Although ALI/ARDS modifying pharmacological agents have been identified in COVID-related disease, the data in non-COVID ALI/ARDS has been less compelling. The increased use of more specific molecular phenotyping based on physiologic parameters and biomarkers, will ensure equipoise between groups, and will likely allow more precision in confirming pharmacological agent efficacy in future studies.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139691615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Kallikrein inhibitors for angioedema: the progress of preclinical and early phase studies. 治疗血管性水肿的 Kallikrein 抑制剂：临床前和早期阶段研究的进展。

IF 6.1 2区医学

Expert opinion on investigational drugs Pub Date : 2024-03-01 Epub Date: 2024-02-26 DOI: 10.1080/13543784.2024.2320700

Henriette Farkas, Zsuzsanna Balla

{"title":"Kallikrein inhibitors for angioedema: the progress of preclinical and early phase studies.","authors":"Henriette Farkas, Zsuzsanna Balla","doi":"10.1080/13543784.2024.2320700","DOIUrl":"10.1080/13543784.2024.2320700","url":null,"abstract":"Introduction: Hereditary angioedema (HAE) is a rare genetic disorder characterized by recurrent edema and predominantly caused by the dysregulation of the kinin-kallikrein system.Areas covered: This manuscript presents the results of preclinical and early clinical trials of newer drugs targeting the dysregulated kinin-kallikrein system. ATN-249 is an oral drug that has shown promising results in preclinical and Phase I studies, and good tolerability in the prophylactic treatment of attacks. KVD900 is also an oral agent developed for the on-demand treatment of HAE attacks. It has shown positive results in Phase I/II studies, with rapid absorption. The third drug, IONIS-PKKRx, is an antisense oligonucleotide targeting plasma prekallikrein mRNA. It has shown a dose-dependent reduction of plasma prekallikrein levels and proenzyme activation in Phase I/II studies, and has shown promising results. STAR-0215 is a long acting anti-activated kallikrein monoclonal antibody. A Phase 1a single ascending dose trial evaluated its safety, pharmacokinetics, and pharmacodynamics. Lastly, NTLA-2002 is an investigational gene-editing therapy.Expert opinion: The targeted treatment of the dysregulated kinin-kallikrein system with specific inhibitors is promising for the prevention of angioedema attacks. Ongoing phase III studies will provide further insight into the efficacy and long-term safety of these novel therapies, potentially expanding treatment options for HAE treatment.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139898009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A modest proposal: targeting αv integrin-mediated activation of latent TGFbeta as a novel therapeutic approach to treat scleroderma fibrosis. 一个微不足道的建议：将αv整合素介导的潜伏TGFbeta激活作为治疗硬皮病纤维化的新疗法。

IF 6.1 2区医学

Expert opinion on investigational drugs Pub Date : 2024-03-01 Epub Date: 2024-02-26 DOI: 10.1080/13543784.2024.2323528

Andrew Leask, Asmaa Fadl, Angha Naik

引用次数: 0

Taletrectinib for the treatment of ROS-1 positive non-small cell lung cancer: a drug evaluation of phase I and II data. 治疗 ROS-1 阳性非小细胞肺癌的 Taletrectinib：对 I 期和 II 期数据的药物评估。

IF 6.1 2区医学

Expert opinion on investigational drugs Pub Date : 2024-02-01 Epub Date: 2024-01-29 DOI: 10.1080/13543784.2024.2305131

Misako Nagasaka, Danielle Brazel, Sai-Hong Ignatius Ou

{"title":"Taletrectinib for the treatment of ROS-1 positive non-small cell lung cancer: a drug evaluation of phase I and II data.","authors":"Misako Nagasaka, Danielle Brazel, Sai-Hong Ignatius Ou","doi":"10.1080/13543784.2024.2305131","DOIUrl":"10.1080/13543784.2024.2305131","url":null,"abstract":"Introduction: While crizotinib and entrectinib have been approved to treat ROS1 fusion-positive (ROS1+) non-small-cell lung cancer (NSCLC), unmet needs remain. These unmet needs include treatment options for patients with resistance mutations and efficacious options even in the presence of brain metastasis while simultaneously avoiding unwanted neurological side effects.Areas covered: Taletrectinib was designed to: improve efficacy; overcome resistance to first-generation ROS1 inhibitors; and address central nervous system penetration while conferring fewer neurological adverse events. All of these features are demonstrated and supported by data from the phase I and the regional phase II TRUST-I clinical trial. Here, we describe the preclinical and clinical characteristics of taletrectinib and evaluate the data from phase I and II studies and review the rationale and design of TRUST-II, a global phase II study of taletrectinib, which is enrolling patients in North America, Europe, and Asia.Expert opinion: Taltrectinib has the potential to improve PFS based on its greater potency against ROS1+ tumors and high CNS penetration. By selectively inhibiting ROS1 wild-type and its resistant mutations over TRKB, taltrectinib has a better safety profile with minimal CNS-related AEs compared to other ROS1+ inhibitors.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139466342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Islatravir: evaluation of clinical development for HIV and HBV. Islatravir：艾滋病毒和 HBV 临床开发评估。

IF 6.1 2区医学

Expert opinion on investigational drugs Pub Date : 2024-02-01 Epub Date: 2024-01-26 DOI: 10.1080/13543784.2024.2305130

Samuel W Gillespie, Athreya S Reddy, Dana M Burris, S Hasan Naqvi, Siddappa N Byrareddy, Christian L Lorson, Kamal Singh

{"title":"Islatravir: evaluation of clinical development for HIV and HBV.","authors":"Samuel W Gillespie, Athreya S Reddy, Dana M Burris, S Hasan Naqvi, Siddappa N Byrareddy, Christian L Lorson, Kamal Singh","doi":"10.1080/13543784.2024.2305130","DOIUrl":"10.1080/13543784.2024.2305130","url":null,"abstract":"Introduction: Islatravir (ISL) is a nucleoside reverse transcriptase translocation inhibitor (NRTTI) that inhibits HIV RT through multiple mechanisms. Contrary to all approved NtRTIs, islatravir retains a 3'OH group. In vitro and clinical data show that ISL is an ultrapotent investigational drug with high tolerability.Areas covered: The historical development of islatravir and its mechanisms of HIV and HBV inhibition and resistance are covered. Additionally, the outcomes of Phase I and Phase II clinical trials are discussed.Expert opinion: Current first-line antiretroviral therapy, preexposure, and postexposure prophylactic interventions are highly effective in maintaining low or undetectable viral load. Despite these measures, an unusually high rate of new infections every year warrants developing novel antivirals that can suppress drug-resistant HIV and improve compliance. ISL, an NRTTI once deemed a long-acting drug, was placed on a clinical hold. The outcome of ongoing clinical trials with a reduced ISL dose will decide its future clinical application. Additionally, MK-8527, which inhibits HIV via same mechanism as that of ISL may supersede ISL. Data on ISL inhibition of HBV are scarce, and preclinical data show dramatically lower ISL efficacy against HBV than currently preferred nucleos(t)ide drugs, indicating that ISL may not be a potent anti-HBV drug.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139485495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Potential of BGB-11417, a BCL2 inhibitor, in hematological malignancies. BCL2抑制剂BGB-1417在血液恶性肿瘤中的潜力。

IF 6.1 2区医学

Expert opinion on investigational drugs Pub Date : 2024-02-01 Epub Date: 2024-01-26 DOI: 10.1080/13543784.2024.2309873

Antonella Bruzzese, Enrica Antonia Martino, Caterina Labanca, Francesco Mendicino, Eugenio Lucia, Virginia Olivito, Antonino Neri, Fortunato Morabito, Ernesto Vigna, Massimo Gentile

引用次数: 0

Progress in the treatment of anal cancer: an overview of the latest investigational drugs. 肛门癌治疗进展：最新研究药物概览。

IF 6.1 2区医学

Expert opinion on investigational drugs Pub Date : 2024-02-01 Epub Date: 2024-01-30 DOI: 10.1080/13543784.2024.2311191

James Yu, Richard D Kim

{"title":"Progress in the treatment of anal cancer: an overview of the latest investigational drugs.","authors":"James Yu, Richard D Kim","doi":"10.1080/13543784.2024.2311191","DOIUrl":"10.1080/13543784.2024.2311191","url":null,"abstract":"Introduction: Anal cancer, a rare malignancy accounting for 2.5-3.0% of gastrointestinal cancers, primarily manifests as squamous cell carcinoma associated with HPV. Recent years have witnessed significant advancements in managing squamous cell carcinoma of the anus (SCCA), particularly with the introduction of immune checkpoint inhibitors (ICIs) and randomized data on front-line chemotherapy.Areas covered: This review discusses the current standard treatments for both early and advanced SCCA, based on published data. The authors then describe the new approaches, focusing on ICI combinations, targeted agents, T-cell adoptive therapy, and HPV-therapeutic vaccines.Expert opinion: The current standard treatment for SCCA includes front-line carboplatin and paclitaxel, with pembrolizumab and nivolumab as later-line options. While modified DCF has shown promise in single-arm studies, its role as a front-line therapy requires confirmation through randomized data. We eagerly anticipate the results of phase 3 trials investigating the front-line chemo-immunotherapy for metastatic SCCA and ICI consolidation following chemoradiation for early-stage SCCA. Novel approaches like T-cell adoptive therapy, HPV-therapeutic vaccines, and bifunctional antibodies combined with HPV vaccines are in early-stage trials for HPV-mediated tumors, including HPV-positive SCCA. These approaches targeting HPV epitopes may eventually gain tumor-agnostic approval, although their role in SCCA may take time to establish.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139563601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Correction. 更正。

IF 6.1 2区医学

Expert opinion on investigational drugs Pub Date : 2024-02-01 Epub Date: 2024-02-19 DOI: 10.1080/13543784.2024.2319956

引用次数: 0