Expert opinion on investigational drugs最新文献

Prospects of current AXL-targeting therapies in early phase cancer trials. 当前axl靶向治疗在早期癌症试验中的前景。

IF 4.9 2区医学

Expert opinion on investigational drugs Pub Date : 2025-05-31 DOI: 10.1080/13543784.2025.2511178

Juhye Yim, Chloe Hope, Justus M Huelse, Douglas K Graham

{"title":"Prospects of current AXL-targeting therapies in early phase cancer trials.","authors":"Juhye Yim, Chloe Hope, Justus M Huelse, Douglas K Graham","doi":"10.1080/13543784.2025.2511178","DOIUrl":"10.1080/13543784.2025.2511178","url":null,"abstract":"Introduction: AXL, a member of the TAM (TYRO3, AXL, and MERTK) family of receptor tyrosine kinases, controls pro-tumorigenic signaling cascades and cancer-immunological functions, and promotes drug resistance. Due to AXL's multifaceted role and therapeutic activity in preclinical studies, a variety of AXL inhibitors are being developed and tested in clinical trials for cancer treatment. Some clinical studies are showing promising results for AXL inhibitors as monotherapy and in combination with standard of care therapeutics. Currently, no selective AXL-targeting therapy has reached FDA-approval, but several compounds have entered phase II and III studies.Area covered: We elaborate on the role of AXL in cancer progression and suppressing anti-cancer immunity at both the molecular level and immune cell interaction level. Additionally, we review pre-clinical and clinical data of AXL-targeting agents.Expert opinion: Preclinical and several early clinical trials demonstrated the safety of AXL-targeting monotherapies with some evidence of efficacy. Additionally, multiple novel combination regimens including AXL-targeting agents to overcome resistance mechanisms are being actively examined with some promising results. However, patient selection and companion biomarkers may be critical for the success of AXL-targeting therapies.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"1-33"},"PeriodicalIF":4.9,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141807","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 : 2025-05-31 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":"https://doi.org/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 [6].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":""},"PeriodicalIF":4.9,"publicationDate":"2025-05-31","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

Prospects for multi-focal motor neuropathy treatment by complement inhibition. 补体抑制治疗多灶性运动神经病的前景。

IF 4.9 2区医学

Expert opinion on investigational drugs Pub Date : 2025-05-30 DOI: 10.1080/13543784.2025.2511177

Hans Katzberg, Carlos Alberto Soto Rincón

引用次数: 0

Clinical progress of B7-H3 targeted antibody drug conjugate ifinatamab deruxtecan for small-cell lung cancer. B7-H3靶向抗体药物偶联物德鲁德替康治疗小细胞肺癌的临床进展

IF 4.9 2区医学

Expert opinion on investigational drugs Pub Date : 2025-05-29 DOI: 10.1080/13543784.2025.2512566

Mylène Wespiser, Romane Gille, Maurice Pérol

{"title":"Clinical progress of B7-H3 targeted antibody drug conjugate ifinatamab deruxtecan for small-cell lung cancer.","authors":"Mylène Wespiser, Romane Gille, Maurice Pérol","doi":"10.1080/13543784.2025.2512566","DOIUrl":"10.1080/13543784.2025.2512566","url":null,"abstract":"Introduction: Small cell lung cancer is an aggressive malignancy with limited treatment options and poor prognosis, particularly at extensive stage. While first-line platinum-etoposide chemotherapy combined with anti-PD-L1 therapy improves survival, most patients relapse, highlighting the need for novel therapies.Areas covered: B7-Homolog3 (B7-H3), an immune checkpoint molecule overexpressed in SCLC, has emerged as a promising therapeutic target. Ifinatamab deruxtecan (I-DXd) is an antibody-drug conjugate targeting B7-H3, delivering a topoisomerase I inhibitor. Early clinical trials (IDeate-PanTumor01 and IDeate-Lung01) have demonstrated encouraging results in pretreated ES-SCLC. In the 12 mg/kg cohort of IDeate-Lung01, I-DXd achieved an objective response rate of 54.8%, median progression-free survival of 5.5 months, and median overall survival of 11.8 months. Notably, it showed intracranial activity with a central nervous system-confirmed response rate of 37.8%.Expert opinion: I-DXd is currently being evaluated in the phase III IDeate-Lung02 trial. Its promising efficacy, manageable safety profile, and potential in combination strategies position it as a key candidate for future SCLC treatment.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"1-9"},"PeriodicalIF":4.9,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150001","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 : 2025-05-28 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":"1-11"},"PeriodicalIF":4.9,"publicationDate":"2025-05-28","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

Safety, pharmacokinetics, and efficacy of HY-072808 ointment, a novel PDE4 inhibitor, in adolescent and adult patients with mild-to-moderate AD. HY-072808软膏（一种新型PDE4抑制剂）在轻中度AD青少年和成人患者中的安全性、药代动力学和疗效

IF 4.9 2区医学

Expert opinion on investigational drugs Pub Date : 2025-05-27 DOI: 10.1080/13543784.2025.2510671

Feng Yao, Mingchao He, Jing Wang, Yao Li, Qian Zhang, Jingjing Yang, Jingying Wu, Qin Zhang, Renpeng Zhou, Meiling Zhang, Linying Meng, Liming Wu, Zhaoxing Chu, Wei Hu

{"title":"Safety, pharmacokinetics, and efficacy of HY-072808 ointment, a novel PDE4 inhibitor, in adolescent and adult patients with mild-to-moderate AD.","authors":"Feng Yao, Mingchao He, Jing Wang, Yao Li, Qian Zhang, Jingjing Yang, Jingying Wu, Qin Zhang, Renpeng Zhou, Meiling Zhang, Linying Meng, Liming Wu, Zhaoxing Chu, Wei Hu","doi":"10.1080/13543784.2025.2510671","DOIUrl":"10.1080/13543784.2025.2510671","url":null,"abstract":"Background: HY-072808 is a new PDE4 inhibitor with potential anti- atopic dermatitis (AD) effects. This study aimed to investigate its safety and pharmacokinetics in healthy individuals, and subsequently, its safety, pharmacokinetics, and efficacy in patients with mild-to-moderate AD.Methods: We conducted double-blind, placebo-controlled, single and multiple ascending dose phase I clinical trials to assess the safety and pharmacokinetics of HY-072808 ointment in healthy subjects, followed by an open-label trial to evaluate its safety, pharmacokinetics, and efficacy in adolescent and adult patients with mild-to-moderate AD. The trials included 73 healthy subjects and 20 patients with AD.Results: We found that HY-072808 had a favorable safety profile, with mild and manageable adverse events reported in both healthy subjects and AD patients. The pharmacokinetic analysis revealed that systemic exposure to HY-072808 remained minimal, with drug concentrations staying in the nanogram range. Furthermore, significant improvements in eczema severity, pruritus, and quality of life were observed in patients with mild-to-moderate AD, with 57.9% of patients achieving a ≥ 75% reduction in the EASI score.Conclusion: These results indicate the potential of HY-072808 as an effective and well-tolerated treatment for mild-to-moderate AD, suggesting further clinical development for use in both adolescent and adult patients.Trial registration: Chinese Clinical Trial Registry (No. ChiCTR2400087123).","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"1-13"},"PeriodicalIF":4.9,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144136189","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 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 : 2025-05-27 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":"https://doi.org/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 heparinsulfate 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":""},"PeriodicalIF":4.9,"publicationDate":"2025-05-27","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

Clinical development of tri-specific antibodies for immune-oncology. 免疫肿瘤学三特异性抗体的临床发展。

IF 4.9 2区医学

Expert opinion on investigational drugs Pub Date : 2025-05-25 DOI: 10.1080/13543784.2025.2511180

Zhipeng Cao, Laura D Osellame, Laura Allan, Andrew M Scott

引用次数: 0

Role of ROCK2 inhibitors in the treatment of chronic graft-versus-host disease. ROCK2抑制剂在慢性移植物抗宿主病治疗中的作用

IF 4.9 2区医学

Expert opinion on investigational drugs Pub Date : 2025-05-25 DOI: 10.1080/13543784.2025.2510667

Dat Ngo, Jose Tinajero, Salman Otoukesh, Karamjeet Sandhu, Haris Ali, Shukaib Arslan, Badri Modi, Idoroenyi Amanam, Ryotaro Nakamura, Amandeep Salhotra

{"title":"Role of ROCK2 inhibitors in the treatment of chronic graft-versus-host disease.","authors":"Dat Ngo, Jose Tinajero, Salman Otoukesh, Karamjeet Sandhu, Haris Ali, Shukaib Arslan, Badri Modi, Idoroenyi Amanam, Ryotaro Nakamura, Amandeep Salhotra","doi":"10.1080/13543784.2025.2510667","DOIUrl":"10.1080/13543784.2025.2510667","url":null,"abstract":"Introduction: Chronic graft-versus-host disease (cGVHD) is the most common cause of late non-relapse mortality after allogeneic hematopoietic cell transplantation (allo-HCT). Rho-associated coiled-coiled kinases (ROCK) inhibitors have been shown to balance the pro-inflammatory and regulatory T-cell subsets in addition to reducing fibrosis in cGVHD, resulting in the development of multiple ROCK2 inhibitors including belumosudil.Areas covered: We describe the pathophysiology of cGVHD and the role of ROCK2 in cGVHD. This includes a review of the current and ongoing clinical data with belumosudil, and an overview of current ROCK2 inhibitors in development for cGVHD, including rovadicitinib, zelasudil, and GV-101.Expert opinion: Many of the recent novel agents with unique mechanisms such as ROCK2 inhibitors (i.e. belumosudil) provide high response rates but rarely yield complete responses in cGVHD. The future of management of cGVHD will rely on investigating combination therapy upfront that may achieve deeper complete responses, developing newer preventative therapies, and advancements in biomarker detection/risk stratification for cGVHD.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"1-10"},"PeriodicalIF":4.9,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144127065","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 development of siRNA conjugates to target tumor antigens. 靶向肿瘤抗原的siRNA偶联物的临床前开发。

IF 4.9 2区医学

Expert opinion on investigational drugs Pub Date : 2025-05-24 DOI: 10.1080/13543784.2025.2511181

Takanori Kubo, Toshio Seyama

引用次数: 0