Expert opinion on investigational drugs最新文献_第2页

A VEGF gene therapy approach for the treatment of patients with coronary artery disease and refractory angina: assessment of clinical development. 血管内皮生长因子基因治疗冠状动脉疾病和难治性心绞痛：临床进展评估

IF 4.9 2区医学

Expert opinion on investigational drugs Pub Date : 2025-05-01 Epub Date: 2025-05-27 DOI: 10.1080/13543784.2025.2510666

Raviteja R Guddeti, Alan Wong, Steven Rudick, Geoffrey Answini, Eric Duckers, Howard C Dittrich, Timothy D Henry

{"title":"A VEGF gene therapy approach for the treatment of patients with coronary artery disease and refractory angina: assessment of clinical development.","authors":"Raviteja R Guddeti, Alan Wong, Steven Rudick, Geoffrey Answini, Eric Duckers, Howard C Dittrich, Timothy D Henry","doi":"10.1080/13543784.2025.2510666","DOIUrl":"10.1080/13543784.2025.2510666","url":null,"abstract":"Introduction: Vascular endothelial growth factor (VEGF) gene therapy is a novel treatment strategy for refractory angina (RA) that works by promoting myocardial neoangiogenesis and collateral circulation formation. XC001 (encoberminogene rezmadenovec) is a novel, replication-deficient, non-integrating recombinant adenovirus vector formally referred to as AdVEGF-All6A+ engineered to produce three isoforms of VEGF A (121, 165, and 189) that are proven to induce neoangiogenesis and constructed specifically to increase the expression of VEGF 189 and 165 to improve safety because of its heparan sulfate binding domain.Areas covered: We review the clinical development of XC001 and results of the EXACT (Epicardial delivery of encoberminogene rezmadenovec [XC001] gene therapy for refractory Angina Coronary Treatment) phase 1 and phase 2 trials.Expert opinion: In initial trials, intramyocardial XC001 has been shown to be safe with signals for efficacy in decreasing myocardial perfusion defects, improving exercise duration, and anginal complaints in patients with RA. A Phase 2 trial using a novel percutaneous delivery catheter for endomyocardial delivery of XC001 is currently underway and has potential benefits in multiple other conditions, including as an adjunct therapy in patients undergoing CABG treatment at risk for incomplete revascularization, patients with coronary microvascular dysfunction, and others with peripheral arterial disease.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"363-370"},"PeriodicalIF":4.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150000","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 randomized, Phase I study of the safety, tolerability, and pharmacokinetics of BI 764198, a transient receptor potential channel 6 (TRPC6) inhibitor, in healthy Japanese men. BI 764198（一种瞬时受体电位通道6 （TRPC6）抑制剂）在日本健康男性中的安全性、耐受性和药代动力学的随机I期研究

IF 4.9 2区医学

Expert opinion on investigational drugs Pub Date : 2025-05-01 Epub Date: 2025-06-03 DOI: 10.1080/13543784.2025.2510664

Takuma Yonemura, Akiko Sarashina, Yoshifumi Tachibana, Silke Retlich, Nima Soleymanlou

{"title":"A randomized, Phase I study of the safety, tolerability, and pharmacokinetics of BI 764198, a transient receptor potential channel 6 (TRPC6) inhibitor, in healthy Japanese men.","authors":"Takuma Yonemura, Akiko Sarashina, Yoshifumi Tachibana, Silke Retlich, Nima Soleymanlou","doi":"10.1080/13543784.2025.2510664","DOIUrl":"10.1080/13543784.2025.2510664","url":null,"abstract":"Background: BI 764198 is a selective, oral transient receptor potential cation channel, subfamily C, member 6 inhibitor under investigation for focal segmental glomerulosclerosis.Research design and methods: Phase I study in 44 Japanese male volunteers. Single dose part: BI 764198 20 mg (n = 6) vs. placebo (n = 2); multiple dose part: BI 764198 40, 80, or 160 mg (n = 9 each) or placebo (n = 9) as a single dose then multiple daily dosing for 2 weeks. Primary endpoint: participants with drug-related adverse events (DRAEs); secondary endpoints: pharmacokinetic.Results: DRAEs were reported in 20.5% (9/44) of participants (total BI 764198 21.2% [7/33]; placebo 18.2% [2/11]), mostly diarrhea (total BI 764198 15.2% [5/33]; placebo 18.2% [2/11]) and headache (BI 764198 80 mg 11.1% [1/9]; BI 764198 160 mg 33.3% [3/9]). BI 764198 exposure increased near dose proportionally to 80 mg and was slightly higher than anticipated with 160 mg. Pharmacokinetics were similar in Asians and non-Asians after accounting for body weight. Limitations include small sample size per dose and short trial duration.Conclusions: BI 764198 was well tolerated; exposure increased near dose proportionally to 80 mg, as previously observed in predominantly White volunteers.Clinical trial registration: This study was registered on Clinical Trials.gov, identifier NCT04665700.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"425-433"},"PeriodicalIF":4.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144119270","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

Emerging GPRC5D-Targeted therapies for multiple myeloma: a comprehensive review. 新兴的gprc5d靶向治疗多发性骨髓瘤：全面回顾。

IF 4.9 2区医学

Expert opinion on investigational drugs Pub Date : 2025-05-01 Epub Date: 2025-05-28 DOI: 10.1080/13543784.2025.2511179

Darren Pan, Anupama Kumar, Jodi J Lipof, Alfred Chung, Jeffrey L Wolf, Thomas G Martin, Shagun Arora, Peter H Sayre, Ajai Chari

{"title":"Emerging GPRC5D-Targeted therapies for multiple myeloma: a comprehensive review.","authors":"Darren Pan, Anupama Kumar, Jodi J Lipof, Alfred Chung, Jeffrey L Wolf, Thomas G Martin, Shagun Arora, Peter H Sayre, Ajai Chari","doi":"10.1080/13543784.2025.2511179","DOIUrl":"10.1080/13543784.2025.2511179","url":null,"abstract":"Introduction: GPRC5D is a promising myeloma-associated antigen, and several GPRC5D-targeted therapies are under active investigation, including CAR T cells, bispecific and trispecific antibodies, and antibody-drug conjugates. This class of agents is poised to transform the landscape of multiple myeloma treatment.Areas covered: Here, we review the biology of GPRC5D, the current and emerging uses of talquetamab in relapsed/refractory multiple myeloma, the landscape of investigational GPRC5D-targeted drugs, and how these agents are likely to be implemented into future clinical practice.Expert opinion: Talquetamab is currently the only approved GPRC5D-targeted therapy, primarily used for BCMA-refractory multiple myeloma, but there is no biological reason BCMA therapies must be exhausted before targeting GPRC5D; utilizing GPRC5D in innovative ways will be key to fully realizing its therapeutic potential. Newer trials are exploring more aggressive approaches combining multiple immunotherapy targets within a single line to prevent resistance and potentially achieve a cure. While GPRC5D-targeted therapies are highly effective, they also pose significant toxicity risks including oral, skin, nail, and cerebellar toxicity. In addition to improving efficacy, future research must also focus on optimizing dosing, identifying biomarkers for toxicity, and developing better strategies for managing adverse events to optimize the risk-benefit profile of these therapies.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"379-389"},"PeriodicalIF":4.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144157644","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

Treating KRAS G12C lung cancer: therapeutic potential of investigation drugs in early clinical study. 治疗KRAS G12C肺癌：研究药物在早期临床研究中的治疗潜力。

IF 4.9 2区医学

Expert opinion on investigational drugs Pub Date : 2025-05-01 Epub Date: 2025-06-02 DOI: 10.1080/13543784.2025.2511175

Kendra Wilson, Jesus Salvador Flores Banda, Fatima Raza, Sanjana Bukkapatnam, Sanjana Gangane, Erminia Massarelli

{"title":"Treating KRAS G12C lung cancer: therapeutic potential of investigation drugs in early clinical study.","authors":"Kendra Wilson, Jesus Salvador Flores Banda, Fatima Raza, Sanjana Bukkapatnam, Sanjana Gangane, Erminia Massarelli","doi":"10.1080/13543784.2025.2511175","DOIUrl":"10.1080/13543784.2025.2511175","url":null,"abstract":"Introduction: The KRAS (Kirsten rat sarcoma viral oncogene homolog) gene is recognized as the most frequently mutated oncogene in advanced non-small cell lung cancer (NSCLC). The most prevalent mutation within this gene is G12C, formally known as KRAS G12C, which leads to the substitution of glycine with cysteine at position 12 of the KRAS protein.Areas covered: Recent advancements in research have developed effective therapies designed to inhibit activated KRAS signaling. As a result, the first two accelerated FDA-approved KRAS inhibitors, sotorasib, and adagrasib have been successfully introduced to the market for locally advanced or metastatic KRAS G12C mutated NSCLC who progressed after prior therapy. A second generation of KRAS inhibitors is currently being tested in clinical trials, and in combination with immunotherapy and chemotherapy.Expert opinion: Future research is crucial to determine the optimal timing for treatment with KRAS G12C inhibitors. Additional studies are needed to identify biomarkers that predict which patients will benefit most. This review discusses and analyzes both completed and ongoing clinical trials of first and second-generation KRAS inhibitors. It also addresses mechanisms of resistance to KRAS inhibition, potential therapeutic strategies to overcome this resistance, biomarkers, side effects, and its role in central nervous system metastatic disease.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"401-413"},"PeriodicalIF":4.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144191709","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

Zelenectide pevedotin (BT-8009): a bicyclic peptide toxin conjugate targeting nectin-4 for the treatment of bladder cancer. Zelenectide pevedotin (BT-8009)：一种靶向nectin-4治疗膀胱癌的双环肽毒素偶联物。

IF 4.9 2区医学

Expert opinion on investigational drugs Pub Date : 2025-05-01 Epub Date: 2025-06-14 DOI: 10.1080/13543784.2025.2510669

Antonio Cigliola, Valentina Tateo, Michela Ravasi, Giorgia Di Maria, Serena Manzo, Brigida Anna Maiorano, Chiara Mercinelli, Andrea Necchi

{"title":"Zelenectide pevedotin (BT-8009): a bicyclic peptide toxin conjugate targeting nectin-4 for the treatment of bladder cancer.","authors":"Antonio Cigliola, Valentina Tateo, Michela Ravasi, Giorgia Di Maria, Serena Manzo, Brigida Anna Maiorano, Chiara Mercinelli, Andrea Necchi","doi":"10.1080/13543784.2025.2510669","DOIUrl":"10.1080/13543784.2025.2510669","url":null,"abstract":"Introduction: Zelenectide pevedotin (BT8009) is a novel Bicycle Toxin Conjugate targeting nectin-4, designed to overcome the limitations of already existing anti-nectin-4 antibody-drug conjugates such as enfortumab vedotin (EV). Its innovative molecular design enhances tumor penetration, minimizes systemic toxicity, and achieves therapeutic efficacy independent from internalization.Areas covered: This review evaluates the preclinical rationale and clinical data for BT8009, focusing on its pharmacokinetic properties, safety, and efficacy compared to EV. Key findings from the ongoing phase I/II Duravelo-1 trial are analyzed alongside challenges in the design of the phase II/III Duravelo-2 trial and their potential implications for future clinical development.Expert opinion: Preliminary data on BT8009 reveal an intriguing clinical profile, with promising efficacy and a notable safety profile. However, the design of ongoing trials raises concerns, particularly due to the use of outdated control arms and the lack of direct comparisons to EV. These limitations could delay its clinical adoption and regulatory approval, impacting on its positioning in an increasingly competitive therapeutic landscape. Nonetheless, if ongoing and future trials confirm its efficacy and safety advantages, BT8009 could represent a valuable advancement for the treatment of nectin-4 expressing solid tumors such as urothelial carcinoma, warranting further investigation in more robust comparative studies.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"371-378"},"PeriodicalIF":4.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144119271","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

Phase 1 trials of BI 764198, a transient receptor potential channel 6 inhibitor, in healthy volunteers and participants with kidney impairment. BI 764198是一种瞬时受体电位通道6抑制剂，在健康志愿者和肾损害患者中进行一期试验。

IF 4.9 2区医学

Expert opinion on investigational drugs Pub Date : 2025-05-01 Epub Date: 2025-06-08 DOI: 10.1080/13543784.2025.2510673

Armin Schultz, Atef Halabi, Friedeborg Seitz, Katrien Lemmens, Hauke S Wülfrath, Maximilian T Lobmeyer, Silke Retlich, Wansuk Choi, Nima Soleymanlou

{"title":"Phase 1 trials of BI 764198, a transient receptor potential channel 6 inhibitor, in healthy volunteers and participants with kidney impairment.","authors":"Armin Schultz, Atef Halabi, Friedeborg Seitz, Katrien Lemmens, Hauke S Wülfrath, Maximilian T Lobmeyer, Silke Retlich, Wansuk Choi, Nima Soleymanlou","doi":"10.1080/13543784.2025.2510673","DOIUrl":"10.1080/13543784.2025.2510673","url":null,"abstract":"Background: BI 764198 could reduce podocyte injury in focal segmental glomerulosclerosis (FSGS).Research design and methods: Four Phase 1 BI 764198 trials: single rising dose (SRD) and multiple rising dose (MRD)/drug-drug interaction trials in healthy volunteers; relative bioavailability (rBA) study (food and formulations effects on pharmacokinetics; PK); and kidney impairment (KI) PK study.Results: SRD trial: 4/54 BI 764198-treated participants (7.4%) had ≥ 1 investigator-defined drug-related adverse event (DRAE): headache (n = 3; 5.6%); diarrhea (n = 1; 16.7%). BI 764198 PK was approximately linear. MRD trial: DRAEs occurred in 5/32 (15.6%) participants receiving BI 764198 and 1/8 (12.5%) receiving placebo. Once-daily BI 764198 80 mg (10 days) did not alter midazolam PK. All BI 764198 formulations tested had similar rBA; food did not affect PK. KI study: geometric mean ratios for area under the plasma concentration-time curve were 147.8% and 177.7% for participants with moderate and severe KI, respectively (vs. without). Limitations include typically small Phase 1 sample sizes and open-label design for the rBA and KI trials.Conclusions: BI 764198 was well tolerated and could be taken with/without food; evaluation in FSGS is ongoing.Clinical trial registration: The trials are registered at www.clinicaltrials.gov with codes NCT03854552; NCT04102462; NCT04656288; NCT04176536.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"415-423"},"PeriodicalIF":4.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144198646","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

Preclinical therapeutics for sickle cell disease: modern developments and future considerations. 镰状细胞病的临床前治疗：现代发展和未来的考虑。

IF 4.9 2区医学

Expert opinion on investigational drugs Pub Date : 2025-04-01 Epub Date: 2025-05-07 DOI: 10.1080/13543784.2025.2500289

Iheanyi Okpala, Charles Nonyelu, Ebele Muoghalu, Ikechukwu Anigbogu, Chinenye Onodugo, Udoka Ilechukwu, Uwaoma Fidelis-Ewa, Augustine Duru, Helen Okoye

{"title":"Preclinical therapeutics for sickle cell disease: modern developments and future considerations.","authors":"Iheanyi Okpala, Charles Nonyelu, Ebele Muoghalu, Ikechukwu Anigbogu, Chinenye Onodugo, Udoka Ilechukwu, Uwaoma Fidelis-Ewa, Augustine Duru, Helen Okoye","doi":"10.1080/13543784.2025.2500289","DOIUrl":"https://doi.org/10.1080/13543784.2025.2500289","url":null,"abstract":"Introduction: Most of the current treatment modalities for sickle hemoglobinopathy are disease-modifying rather than curative. Therefore, there is a need for effective treatment of complications of sickle cell disease (SCD) that impair quality of life. This need drives the evaluation of preclinical therapeutics in search of new treatment modalities.Areas covered: Interventions are likely to progress from research to clinical practice, their potential impact, and future directions in SCD care: HbF inducers, pyruvate kinase activators, anti-selectin P monoclonal antibodies, allosteric Hb modifiers, proactive treatment of cerebral artery conditional blood velocity, multimodal, and gene therapy. Established treatment modalities (e.g with hydroxyurea) are not included because these have advanced well beyond the preclinical stage of therapeutics. Information dated 2025 backward was obtained from Medline, PubMed, and other public sources.Expert opinion: Places for the conduct of preclinical studies ought to include areas of high SCD prevalence. Limited resources currently hinder universal accessibility of curative SCD therapies in these places. The recent approval of non-viral gene therapy for SCD and the number of preclinical therapeutics in development bring realistic expectation that curative and disease-modifying interventions, such as multimodal therapy and proactive treatment of cerebral artery conditional blood velocity to prevent stroke, will become standard care.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":"34 4","pages":"301-315"},"PeriodicalIF":4.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144001869","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 phase 1, randomized, double-blind, placebo-controlled trial investigating the safety, tolerability, pharmacokinetics, and pharmacodynamics of KN056 (a recombinant human GLP-1 variant Fc fusion protein) in healthy Chinese participants. 一项1期、随机、双盲、安慰剂对照试验，研究了KN056（重组人GLP-1变异体Fc融合蛋白）在中国健康参与者中的安全性、耐受性、药代动力学和药效学。

IF 4.9 2区医学

Expert opinion on investigational drugs Pub Date : 2025-04-01 Epub Date: 2025-05-07 DOI: 10.1080/13543784.2025.2500303

Yuan-Fang Qin, Wen-Hua Zhang, Hao-Nan Zhang, Yu-Wei Li, Wen-Qiao Huang, Jin-Lian Xie, Shuang Yang, Lan-Ni Li, Chang Cui, Qi Pei, Jie Huang, Guo-Ping Yang

{"title":"A phase 1, randomized, double-blind, placebo-controlled trial investigating the safety, tolerability, pharmacokinetics, and pharmacodynamics of KN056 (a recombinant human GLP-1 variant Fc fusion protein) in healthy Chinese participants.","authors":"Yuan-Fang Qin, Wen-Hua Zhang, Hao-Nan Zhang, Yu-Wei Li, Wen-Qiao Huang, Jin-Lian Xie, Shuang Yang, Lan-Ni Li, Chang Cui, Qi Pei, Jie Huang, Guo-Ping Yang","doi":"10.1080/13543784.2025.2500303","DOIUrl":"10.1080/13543784.2025.2500303","url":null,"abstract":"Background: This randomized clinical pharmacology trial investigated the pharmacokinetics (PK), pharmacodynamics (PD), safety, and tolerability of KN056 following single-dose subcutaneous administration in healthy Chinese participants.Methods: Thirty healthy male subjects were randomized to receive a single dose of KN056 (0.5, 1.0, 3.0, 6.0, or 12.0 mg) or placebo. PK and PD parameters, as well as safety and tolerability, were assessed.Results: KN056 exposure increased proportionally with dose, with a half-life ranging from 141 to 188 hours. KN056 was well-tolerated, with gastrointestinal adverse events being the most common, particularly at the highest dose (12.0 mg). In the oral glucose tolerance test, KN056 dose-dependently decreased the AUC on the glucose versus time (gAUC) from baseline within 144 hours post-dosing. Specifically, the maximum reduction was 29.9% (occurring at the 72-hour mark). Body weight decreased within seven days of administration, correlating with dose levels, with a mean reduction of -1.68 kg in the 12.0 mg group; however, no significant change in body weight was observed by the end of the study.Conclusions: KN056 demonstrated favorable PK, PD, and safety profiles in healthy Chinese participants, supporting its potential for once-weekly dosing.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":"34 4","pages":"329-337"},"PeriodicalIF":4.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143980693","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

Unlocking the mechanisms underlying the activity of pembrolizumab plus enfortumab vedotin in patients with urothelial carcinoma. 解锁派姆单抗加维多单抗在尿路上皮癌患者中的活性机制

IF 4.9 2区医学

Expert opinion on investigational drugs Pub Date : 2025-04-01 Epub Date: 2025-02-28 DOI: 10.1080/13543784.2025.2473695

Matteo Santoni, Alessandro Rizzo, Francesco Massari

引用次数: 0

The bispecific antibody AZD0486: an overview of the clinical journey to date with a focus on follicular lymphoma. 双特异性抗体AZD0486：迄今为止针对滤泡性淋巴瘤的临床研究综述。

IF 4.9 2区医学

Expert opinion on investigational drugs Pub Date : 2025-04-01 Epub Date: 2025-05-06 DOI: 10.1080/13543784.2025.2500290

Harry Hambleton, Chan Y Cheah

{"title":"The bispecific antibody AZD0486: an overview of the clinical journey to date with a focus on follicular lymphoma.","authors":"Harry Hambleton, Chan Y Cheah","doi":"10.1080/13543784.2025.2500290","DOIUrl":"https://doi.org/10.1080/13543784.2025.2500290","url":null,"abstract":"Introduction: Follicular lymphoma (FL) is the most common indolent lymphoma. Patients with advanced-stage FL typically respond to therapy, then follow a relapsing/remitting course, with shorter progression-free survival with each subsequent line of therapy. Whilst existing CD19-directed therapies such as CAR T-cell therapy have shown promising efficacy in the management of relapsed/refractory FL, immune-mediated adverse events, such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity (ICANS), are well described. AZD0486 is a fully human bispecific (CD19×CD3) T-cell engager (TCE) that induces T cell-mediated cytotoxicity but with low-affinity binding of CD3, resulting in a reduction in cytokine release.Areas covered: In this review, we describe the key preclinical data for AZD0486 and evaluate in detail the available clinical data from the ongoing phase 1 first-in-human study, including safety, efficacy, pharmacokinetics, and future development plans.Expert opinion: Bispecific TCEs are among the most promising novel therapies in use for the management of relapsed/refractory B-cell lymphomas. AZD0486 results in high complete response rates with low incidence of high-grade immune-mediated toxicity compared to alternative TCE therapies. Importantly, it remains active in patients with lymphomas that have lost CD20 expression, an important mechanism of treatment failure following CD20 targeting TCEs.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":"34 4","pages":"245-252"},"PeriodicalIF":4.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144005268","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