Expert opinion on investigational drugs最新文献_第3页

Investigational new drugs to treat brain metastasis from non-small cell lung cancer. 治疗非小细胞肺癌脑转移的新药研究。

IF 4.1 2区医学

Expert opinion on investigational drugs Pub Date : 2025-07-01 Epub Date: 2025-07-11 DOI: 10.1080/13543784.2025.2532449

Pasquale Vitale, Giuseppe Lamberti, Ilaria di Giovanni, Raffaele Addeo

{"title":"Investigational new drugs to treat brain metastasis from non-small cell lung cancer.","authors":"Pasquale Vitale, Giuseppe Lamberti, Ilaria di Giovanni, Raffaele Addeo","doi":"10.1080/13543784.2025.2532449","DOIUrl":"10.1080/13543784.2025.2532449","url":null,"abstract":"Introduction: Lung cancer is a leading cause of cancer-related mortality. Brain metastasis (BM) has a high incidence in non-small cell lung cancer (NSCLC) and represents a devastating complication associated with poor prognosis and symptoms that significantly reduce the quality of life (QOL) in patients. Managing and controlling BM is critical for prolonging survival and improving QOL. Surgical resection, stereotactic radiosurgery, and whole-brain radiation therapy are key treatment modalities for patients with NSCLC and BM.Areas covered: Molecular targeted drugs developed against driver gene mutations and immune checkpoint inhibitors have shown efficacy against BM. This review examines newly approved therapies by conducting a literature search on these topics. Therefore, it is essential to determine the most appropriate local and systemic therapies and the optimal timing to maximize overall survival and QOL.Expert opinion: Despite the effectiveness of new drugs, a high mortality rate persists. We discuss future strategies for overcoming resistance and progression.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"557-570"},"PeriodicalIF":4.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144607894","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 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 : 2025-06-01 Epub 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":"473-505"},"PeriodicalIF":4.9,"publicationDate":"2025-06-01","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

Acetylcholine and muscarinic receptor targeting in bipolar disorder: does xanomeline-trospium chloride and other investigational muscarinic agonists hold promise as mechanistically informed treatments for manic episodes, mixed features and cognitive deficits in bipolar disorder? 以乙酰胆碱和毒蕈碱受体为靶点治疗双相情感障碍：xanomeline-trospium chloride和其他实验性毒蕈碱受体激动剂是否有望作为治疗躁狂症、混合特征和双相情感障碍认知缺陷的一种机制信息疗法？

IF 4.9 2区医学

Expert opinion on investigational drugs Pub Date : 2025-06-01 Epub Date: 2025-07-11 DOI: 10.1080/13543784.2025.2522885

Roger S McIntyre

{"title":"Acetylcholine and muscarinic receptor targeting in bipolar disorder: does xanomeline-trospium chloride and other investigational muscarinic agonists hold promise as mechanistically informed treatments for manic episodes, mixed features and cognitive deficits in bipolar disorder?","authors":"Roger S McIntyre","doi":"10.1080/13543784.2025.2522885","DOIUrl":"10.1080/13543784.2025.2522885","url":null,"abstract":"Introduction: Xanomeline-trospium chloride (Cobenfy, KarXT) received FDA approval on September 26, 2024, for the treatment of adults with schizophrenia. Xanomeline-trospium chloride is the first muscarinic M1, M4 acetylcholine receptor partial agonist approved to treat schizophrenia. Preliminary evidence also indicates that xanomeline-trospium chloride improves measures of cognition in Alzheimer's disease and schizophrenia.Areas covered: Acetylcholine's physiology as well as evidence implicating disturbance in acetylcholine availability and/or its canonical receptors in mania and cognitive impairment in bipolar disorder is synthesized. Extant efficacy, safety and tolerability data for xanomeline-trospium chloride in adults with schizophrenia are reviewed. Xanomeline-trospium chloride's clinical and pharmacological profile provides rationale for investigating its efficacy, safety and tolerability in the treatment of manic episodes, mixed features and cognitive impairment associated with bipolar disorder.Expert opinion: Xanomeline-trospium chloride is a mechanistically novel treatment for schizophrenia targeting cholinergic receptors as opposed to dopamine receptors and may have transdiagnostic efficacy in mania, mixed features and/or cognitive impairment in bipolar disorder. Xanomeline-trospium chloride is safe and generally well tolerated and does not have depressogenic effects and/or increased suicidality in adults with schizophrenia. Whether other investigational muscarinic agonists (e.g. positive allosteric modulator [PAM] or orthosteric agonism of M4) are potentially efficacious in mania and/or cognitive impairment in bipolar disorder is a priority future research avenue.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"519-526"},"PeriodicalIF":4.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324916","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 : 2025-06-01 Epub Date: 2025-05-24 DOI: 10.1080/13543784.2025.2511181

Takanori Kubo, Toshio Seyama

引用次数: 0

A randomized, double-blind, single dose, parallel group, 2-arm study assessing the pharmacokinetic similarity, safety, tolerability, and immunogenicity profiles of biosimilar candidate AVT03 (70 mg/mL) in healthy male adults. 一项随机、双盲、单剂量、平行组、两组研究，评估候选生物类似药AVT03 （70 mg/mL）在健康成年男性中的药代动力学相似性、安全性、耐受性和免疫原性。

IF 4.9 2区医学

Expert opinion on investigational drugs Pub Date : 2025-06-01 Epub Date: 2025-05-16 DOI: 10.1080/13543784.2025.2505469

Monika Tomaszewska-Kiecana, Felicitas Bullo, Lukasz Jaskiewicz, Serena Stamatakos, Hendrik Otto, Masna Rai, Abid Sattar, Steffen Leutz, Fausto Berti

{"title":"A randomized, double-blind, single dose, parallel group, 2-arm study assessing the pharmacokinetic similarity, safety, tolerability, and immunogenicity profiles of biosimilar candidate AVT03 (70 mg/mL) in healthy male adults.","authors":"Monika Tomaszewska-Kiecana, Felicitas Bullo, Lukasz Jaskiewicz, Serena Stamatakos, Hendrik Otto, Masna Rai, Abid Sattar, Steffen Leutz, Fausto Berti","doi":"10.1080/13543784.2025.2505469","DOIUrl":"10.1080/13543784.2025.2505469","url":null,"abstract":"Background: This study (NCT05876949) compared the pharmacokinetic (PK) similarity, safety, and immunogenicity of AVT03, a candidate biosimilar, with reference product (RP) denosumab (Xgeva).Methods: Healthy male participants (N = 208, including 24 Japanese participants) were randomized 1:1 to receive one 120 mg dose of AVT03, or RP. PK similarity was demonstrated if the 90% confidence intervals (CI) for the ratio of geometric means for the primary PK parameters Cmax and AUC0-t were within 80.00% and 125.00%. Additional PK parameters included AUC0-inf, tmax, Kel, t1/2, Vz/F, and CL/F. Safety and immunogenicity were also assessed.Results: The 90% CIs for the ratio of geometric means for the primary PK parameters were entirely contained within the prespecified margins of 80.00% and 125.00% (Cmax [98.26, 110.00]; AUC0-t [102.30, 113.60]), supporting demonstration of PK similarity. Consistency between Japanese participants and the overall population was shown. Safety and immunogenicity profiles were comparable between the two treatment arms.Conclusion: Results supported demonstration of PK similarity between AVT03 and RP. AVT03 had a safety and immunogenicity profile comparable to RP.Clinical trial registration: The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT05876949); and 2022 -003,659-32 (EudraCT).","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"539-546"},"PeriodicalIF":4.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143992716","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

Polyvalent immunoglobulin therapy: preclinical evidence and potential for treating chemotherapy-induced peripheral neuropathy. 多价免疫球蛋白治疗：临床前证据和治疗化疗引起的周围神经病变的潜力。

IF 4.9 2区医学

Expert opinion on investigational drugs Pub Date : 2025-06-01 Epub Date: 2025-06-27 DOI: 10.1080/13543784.2025.2522075

William Moret, Aurore Danigo, Simon Frachet, Franck Sturtz, Sylvie Bourthoumieu, Laurent Magy, Claire Demiot, Amandine Rovini

{"title":"Polyvalent immunoglobulin therapy: preclinical evidence and potential for treating chemotherapy-induced peripheral neuropathy.","authors":"William Moret, Aurore Danigo, Simon Frachet, Franck Sturtz, Sylvie Bourthoumieu, Laurent Magy, Claire Demiot, Amandine Rovini","doi":"10.1080/13543784.2025.2522075","DOIUrl":"10.1080/13543784.2025.2522075","url":null,"abstract":"Introduction: Chemotherapy-induced peripheral neuropathy (CIPN) is a prevalent and often debilitating complication of cancer treatment, affecting over 68% of treated patients. This condition is characterized by sensory deficits, neuropathic pain, and reduced quality of life. While polyvalent human immunoglobulins (IVIg) are established treatments for various immune-mediated neurological disorders, including certain inflammatory and autoimmune peripheral neuropathies, their role in CIPN remains unexplored in clinical settings.Areas covered: This review examines the neuroprotective properties of IVIg, focusing on approved indications, and explores recent preclinical evidence on the role of neuroinflammation in CIPN pathophysiology. We propose that IVIg could, based on preclinical findings, offer therapeutic benefits in managing CIPN without interfering with cancer treatments, provided that future clinical validation supports its efficacy and safety.Expert opinion: Although there is currently no clinical experience with IVIg in CIPN patients, preclinical data suggest promising therapeutic prospects. Future research is essential to elucidate CIPN mechanisms further and to determine how IVIg might contribute as a novel therapeutic strategy, ultimately improving the quality of life for cancer patients.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"507-518"},"PeriodicalIF":4.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505307","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 : 2025-06-01 Epub 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 : 2025-06-01 Epub 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":"463-471"},"PeriodicalIF":4.9,"publicationDate":"2025-06-01","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

A randomized, double-blind, single dose, parallel group, 2-arm study assessing the pharmacokinetic similarity, pharmacodynamic, safety, tolerability, and immunogenicity profiles of biosimilar candidate AVT03 (60 mg/mL) in healthy male adults. 一项随机、双盲、单剂量、平行组、两组研究，评估候选生物类似药AVT03 （60 mg/mL）在健康成年男性中的药代动力学相似性、药效学、安全性、耐受性和免疫原性。

IF 4.9 2区医学

Expert opinion on investigational drugs Pub Date : 2025-06-01 Epub Date: 2025-05-16 DOI: 10.1080/13543784.2025.2505466

Anel Pretorius, Felicitas Bullo, Lukasz Jaskiewicz, Serena Stamatakos, Hendrik Otto, Masna Rai, Ruth Ruffieux, Abid Sattar, Steffen Leutz, Fausto Berti

{"title":"A randomized, double-blind, single dose, parallel group, 2-arm study assessing the pharmacokinetic similarity, pharmacodynamic, safety, tolerability, and immunogenicity profiles of biosimilar candidate AVT03 (60 mg/mL) in healthy male adults.","authors":"Anel Pretorius, Felicitas Bullo, Lukasz Jaskiewicz, Serena Stamatakos, Hendrik Otto, Masna Rai, Ruth Ruffieux, Abid Sattar, Steffen Leutz, Fausto Berti","doi":"10.1080/13543784.2025.2505466","DOIUrl":"10.1080/13543784.2025.2505466","url":null,"abstract":"Background: This study compared pharmacokinetic (PK) similarity, pharmacodynamic, safety, and immunogenicity of AVT03, a candidate biosimilar, with reference product (RP) denosumab (Prolia).Methods: Healthy male participants (N = 209) were randomized 1:1 to receive one 60 mg dose of either AVT03 or RP. PK similarity was demonstrated if the 90% confidence intervals (CI) for the ratio of geometric means for the primary PK parameters (Cmax and AUC0-inf for EMA; Cmax and AUC0-t for FDA and PMDA) were within the prespecified margins of 80.00% and 125.00%. Secondary PK parameters assessed were AUC0-24, Tmax, Kel, t1/2, Vz/F, and CL/F. The serum biomarker of bone resorption, CTX-1 was evaluated to compare pharmacodynamic (PD) profiles. Safety and immunogenicity were also assessed.Results: The 90% CI for the ratio of geometric means for primary PK parameters was contained between the pre-specified margins of 80.00% and 125.00% (Cmax [102.23, 113.64]; AUC0-inf [107.17, 118.87]; AUC0-t [107.72, 120.42]), supporting demonstration of PK similarity between AVT03 and RP. Secondary PK parameters supported the analysis. PD, safety and immunogenicity profiles were comparable between the two arms.Conclusion: Results supported a demonstration of PK similarity between AVT03 and RP denosumab. Comparable PD, safety and immunogenicity profiles were also shown.Clinical trial registration: The clinical trial is registered at https://www.clinicaltrials.gov under identifier NCT05126784.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"527-537"},"PeriodicalIF":4.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143975096","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 : 2025-05-01 Epub 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