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

Clinical development of a CDK8/19 kinase inhibitor for acute myeloid leukemia. CDK8/19激酶抑制剂治疗急性髓性白血病的临床研究

IF 4.1 2区医学

Expert opinion on investigational drugs Pub Date : 2026-04-01 Epub Date: 2026-04-07 DOI: 10.1080/13543784.2026.2656430

Akhil Rajendra, Karen W L Yee

引用次数: 0

Triple negative breast cancer: what clinical progress have we seen in the last 5 years? 三阴性乳腺癌：在过去5年中我们看到了哪些临床进展？

IF 4.1 2区医学

Expert opinion on investigational drugs Pub Date : 2026-03-01 Epub Date: 2026-02-13 DOI: 10.1080/13543784.2026.2629512

Daniel S Peiffer, Maeve A Hennessy, Rita Nanda

{"title":"Triple negative breast cancer: what clinical progress have we seen in the last 5 years?","authors":"Daniel S Peiffer, Maeve A Hennessy, Rita Nanda","doi":"10.1080/13543784.2026.2629512","DOIUrl":"10.1080/13543784.2026.2629512","url":null,"abstract":"Introduction: Triple-negative breast cancer (TNBC) is characterized by the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression. It accounts for ~15% of breast cancer diagnoses, and disproportionally affects young women and those of African and Hispanic ancestry.Areas covered: This review encompasses recent advances in the management of early and advanced-stage TNBC. The identification of distinct molecular subtypes of TNBC has allowed for the optimization of systemic therapy. Distinct drivers of TNBC have been identified, resulting in the regulatory approval of targeted therapies for early and advanced stage disease, including immunotherapy, PARP inhibitors, and antibody-drug conjugates. Literature search was performed using PubMed, and included publications between 01/2010 to 11/2025.Expert opinion: Until recently, the only treatment available for TNBC was chemotherapy. Advances in the molecular characterization of TNBC has revealed distinct subtypes, enabling the development and approval of targeted therapies, including PARP inhibitors, immunotherapy, and antibody-drug conjugates. Treatment options for both early and advanced-stage TNBC are improving, although it remains the subtype with the poorest outcomes. Ongoing trials are focused on personalizing treatment through predictive biomarkers, response-adaptive strategies, and novel agents, with the goal of maximizing efficacy while minimizing toxicity.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"223-238"},"PeriodicalIF":4.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131750","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 IMNN-001 in epithelial ovarian cancer: assessment of clinical findings. IMNN-001在上皮性卵巢癌中的潜在作用：临床结果评估。

IF 4.1 2区医学

Expert opinion on investigational drugs Pub Date : 2026-03-01 Epub Date: 2026-03-11 DOI: 10.1080/13543784.2026.2636926

Premal H Thaker, Stacy R Lindborg, Ana Limon, Douglas V Faller, William H Bradley, Khursheed Anwer, Ronald D Alvarez

{"title":"Potential of IMNN-001 in epithelial ovarian cancer: assessment of clinical findings.","authors":"Premal H Thaker, Stacy R Lindborg, Ana Limon, Douglas V Faller, William H Bradley, Khursheed Anwer, Ronald D Alvarez","doi":"10.1080/13543784.2026.2636926","DOIUrl":"10.1080/13543784.2026.2636926","url":null,"abstract":"Introduction: IMNN-001 is designed for local and durable delivery of a pluripotent anti-tumor cytokine, IL-12, using an expression plasmid and a synthetic lipopolymer delivery system. IMNN-001, delivered intraperitoneally in combination with chemotherapy, is currently in a Phase 3 trial for the front-line treatment of advanced epithelial ovarian cancer.Areas covered: This report details IMNN-001 preclinical and clinical development, demonstrating local and durable production of IL-12, minimal systemic exposure and manageable safety profile, as well as its antitumoral effects in a total of six completed trials in ovarian cancer. In the OVATION-2 Phase 2 randomized trial, neo- and adjuvant chemotherapy combined with IMNN-001 produced a numerical 13 month increase in overall survival, with even greater benefit in tumors that lacked DNA homologous repair activity. In translational studies, IMNN-001-induced changes in the tumor microenvironment are consistent with the observed induction of IL-12 and IFN-γ levels at the tumor site and support the hypothesis that IMNN-001 treatment alters the tumor microenvironment in favor of broad immune stimulation and inhibition of immunosuppressive mechanisms.Expert opinion: IMNN-001 gene therapy could add clinically meaningful IL-12-driven immunotherapy to newly diagnosed ovarian cancer patients. IMNN-001 holds promise for synergistic combinations with immunotherapies requiring intrinsic immune activity.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"191-202"},"PeriodicalIF":4.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147304020","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

Is seltorexant, an orexin-2 receptor antagonist, showing promise in insomnia? seltorexant，一种食欲素-2受体拮抗剂，在治疗失眠方面有前景吗？

IF 4.1 2区医学

Expert opinion on investigational drugs Pub Date : 2026-03-01 Epub Date: 2026-03-05 DOI: 10.1080/13543784.2026.2637841

Sheila A Doggrell

{"title":"Is seltorexant, an orexin-2 receptor antagonist, showing promise in insomnia?","authors":"Sheila A Doggrell","doi":"10.1080/13543784.2026.2637841","DOIUrl":"10.1080/13543784.2026.2637841","url":null,"abstract":"Insomnia is common. Seltorexant (JNJ-42847922), a selective orexin-2 receptor antagonist, was originally trialed in major depression. In a repurposing, seltorexant has been tested in a phase 2b trial for insomnia. This trial represents a new approach to treat insomnia. The primary efficacy endpoint was latency to persistent sleep (LPS) on night 1, which was shortened with seltorexant. In addition to shortening the time to go to sleep in subjects with insomnia, Seltorexant prolonged sleeping time before waking. Comparison showed more benefit and less adverse effects with seltorexant than with zolpidem, an established treatment for insomnia. The findings that (i) the effects of seltorexant may diminish with time, depending on dose and (ii) that the overall incidence of treatment-emergent adverse effects was lower with seltorexant than with placebo, need explanation. A phase 3 trial of seltorexant in depression and insomnia is underway. As seltorexant is showing promise in insomnia, further trials are needed. However, at present, there are no phase 3 clinical trials registered for the treatment of insomnia by seltorexant alone or in comparison with zolpidem, and such trials need consideration.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"211-213"},"PeriodicalIF":4.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147325105","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

Critique of phase II agents for non-small cell lung cancer: what is our clinical need and which agents have potential? 非小细胞肺癌II期药物的评论：我们的临床需要是什么，哪些药物有潜力？

IF 4.1 2区医学

Expert opinion on investigational drugs Pub Date : 2026-03-01 Epub Date: 2026-03-09 DOI: 10.1080/13543784.2026.2636928

Alessia Spagnuolo, Ilaria Spagnoletti, Emanuela Nuccio, Cesare Gridelli

{"title":"Critique of phase II agents for non-small cell lung cancer: what is our clinical need and which agents have potential?","authors":"Alessia Spagnuolo, Ilaria Spagnoletti, Emanuela Nuccio, Cesare Gridelli","doi":"10.1080/13543784.2026.2636928","DOIUrl":"10.1080/13543784.2026.2636928","url":null,"abstract":"Introduction: Phase II studies provide signals that guide therapeutic development for advanced NSCLC. This is particularly important for certain categories of patients, such as those who have already undergone immunotherapy and those with oncogene-addicted disease. However, promising results in phase II often do not translate into equally positive outcomes in phase III and the reason may be related to assay variability, sample heterogeneity, inadequate comparators or optimistic endpoints.Areas covered: This paper provides an overview of treatments for advanced NSCLC and identifies settings where phase II evidence plays a decisive role: post-PD-(L)1/-chemotherapy, post-TKIs, frail patients or patients with brain disease. It also analyzes the reasons behind the failure of phase II success in phase III and proposes what makes a robust signal in phase II, while recognizing the limitations of surrogate endpoints. We take stock of the therapeutic classes that are gaining the most ground and provide a critical assessment of ongoing clinical programs.Expert opinion: At present, a convincing phase II trial in NSCLC is possibly randomized, guided by biomarkers detected by standardized tests, with durable systemic and cerebral activity, inclusion of PROs, and is already in alignment with confirmatory study design and regulatory endpoints.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"239-251"},"PeriodicalIF":4.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147376493","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

Samelisant (SUVN-G3031), a histamine H3 receptor inverse agonist, as a potential treatment for narcolepsy: a phase-2 drug evaluation. Samelisant (SUVN-G3031)，一种组胺H3受体逆激动剂，作为发作性睡病的潜在治疗：2期药物评估

IF 4.1 2区医学

Expert opinion on investigational drugs Pub Date : 2026-03-01 Epub Date: 2026-02-25 DOI: 10.1080/13543784.2026.2634990

Ramakrishna Nirogi, Anil Shinde, Ramkumar Subramanian, Veera Raghava Chowdary Palacharla, Vijay Benade, Renny Abraham, Vinod Kumar Goyal, Pradeep Jayarajan

{"title":"Samelisant (SUVN-G3031), a histamine H3 receptor inverse agonist, as a potential treatment for narcolepsy: a phase-2 drug evaluation.","authors":"Ramakrishna Nirogi, Anil Shinde, Ramkumar Subramanian, Veera Raghava Chowdary Palacharla, Vijay Benade, Renny Abraham, Vinod Kumar Goyal, Pradeep Jayarajan","doi":"10.1080/13543784.2026.2634990","DOIUrl":"10.1080/13543784.2026.2634990","url":null,"abstract":"Introduction: Narcolepsy is a debilitating chronic neurological disorder, and currently, there is no cure. Activation of the histaminergic system through the blockade of histamine 3 (H3) autoreceptors promotes wakefulness. Blockade of H3 heteroreceptors modulates adrenergic, serotonergic, cholinergic, and dopaminergic systems. These properties of H3 receptors may offer therapeutic options for managing the symptoms of narcolepsy. Samelisant is an investigational H3 receptor inverse agonist/antagonist being developed for the treatment of hypersomnia disorders.Areas covered: This review includes an evaluation of the nonclinical and clinical profiles of samelisant.Expert opinion: Samelisant's inverse agonism property at the H3 receptor may be ideal for addressing challenges associated with the constitutive activity. A key distinguishing feature of samelisant is its cleaner drug-drug interaction and cardiovascular safety profile compared to existing treatments. This is particularly important for women of childbearing potential, considering the known interactions of current treatments (e.g. pitolisant and modafinil) with hormonal contraceptives, as well as the common occurrence of polypharmacy and comorbidities in narcolepsy. Additionally, as samelisant may act downstream of orexinergic pathways, it presents an opportunity to complement orexin-based therapies. The potential of samelisant in combination with other narcolepsy treatments represents an important area for future research.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"203-210"},"PeriodicalIF":4.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147270208","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

KAT6 inhibitors under investigation for solid tumors: the preclinical and early phase progress. KAT6抑制剂用于实体瘤的研究：临床前和早期进展

IF 4.1 2区医学

Expert opinion on investigational drugs Pub Date : 2026-03-01 Epub Date: 2026-02-22 DOI: 10.1080/13543784.2026.2634346

Toru Mukohara

{"title":"KAT6 inhibitors under investigation for solid tumors: the preclinical and early phase progress.","authors":"Toru Mukohara","doi":"10.1080/13543784.2026.2634346","DOIUrl":"10.1080/13543784.2026.2634346","url":null,"abstract":"Introduction: KAT6A and its paralog KAT6B (KAT6) are part of the MYST family of histone acetyltransferases. KAT6 is involved in regulating multiple cellular processes by acetylating different lysine residues on histone H3. While KAT6A is overexpressed in various solid tumors, KAT6 is best characterized for its role in ESR1 transcription in estrogen receptor-positive (ER+) breast cancer.Areas covered: Prifetrastat (PF-07248144), a first-in-class KAT6A/B inhibitor, has been tested in a phase I trial, mainly for patients with ER+ breast cancer, and demonstrated promising efficacy with a favorable safety profile, albeit frequent dysgeusia. Prifetrastat in combination with fulvestrant is now being evaluated in a phase III trial for pretreated ER+ advanced breast cancer. In parallel, numerous KAT6 catalytic inhibitors and degraders have entered preclinical and clinical development.Expert opinion: A phase III study of prifetrastat will provide initial data on the clinical significance of KAT6 inhibitors. The application of Prifetrastat and other KAT6 inhibitors to wider breast cancer subpopulations and other solid tumors is anticipated. Additionally, mitigation strategies for dysgeusia and clinically available response-predictive biomarkers should be developed. KAT6 inhibitors with different target spectra, including KAT6A-selective and KAT6/7 inhibitors, may exhibit differential efficacy and safety profiles, offering deeper insights into KAT6-targeted therapy.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"215-221"},"PeriodicalIF":4.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146212731","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

RSV nucleoprotein inhibitors in preclinical to phase II clinical development for respiratory syncytial virus infection. RSV核蛋白抑制剂用于呼吸道合胞病毒感染的临床前到II期临床开发。

IF 4.1 2区医学

Expert opinion on investigational drugs Pub Date : 2026-03-01 Epub Date: 2026-02-24 DOI: 10.1080/13543784.2026.2629509

Ralph A Tripp

引用次数: 0

Optimizing dose selection in oncology: the rationale for the clinical dose selection of giredestrant, an oral selective estrogen receptor degrader. 肿瘤学中的最佳剂量选择：口服选择性雌激素受体降降剂giredestrant临床剂量选择的基本原理。

IF 4.1 2区医学

Expert opinion on investigational drugs Pub Date : 2026-01-01 Epub Date: 2026-02-03 DOI: 10.1080/13543784.2026.2613290

Elgene Lim, Jiajie Yu, Chunze Li, Mona D Shah, Jennifer Eng-Wong, Pablo Diego Pérez-Moreno, Komal Jhaveri

{"title":"Optimizing dose selection in oncology: the rationale for the clinical dose selection of giredestrant, an oral selective estrogen receptor degrader.","authors":"Elgene Lim, Jiajie Yu, Chunze Li, Mona D Shah, Jennifer Eng-Wong, Pablo Diego Pérez-Moreno, Komal Jhaveri","doi":"10.1080/13543784.2026.2613290","DOIUrl":"10.1080/13543784.2026.2613290","url":null,"abstract":"Introduction: 'Maximum tolerated dose' (MTD) was historically used to maximize clinical efficacy. However, there is a drive to optimize dose selection to improve safety/tolerability, while maintaining efficacy. This paradigm is increasingly important in oncology clinical development, leading to a focus on careful early-phase trial design to ensure that appropriate dose - or exposure-response data are obtained to guide dose selection.Areas covered: We describe the development pathway and risk-benefit considerations for clinical dose selection for giredestrant, a next-generation, highly potent, non-steroidal oral selective estrogen receptor antagonist and degrader, under development for estrogen receptor-positive breast cancer. This included evaluating low-grade adverse events to potentially improve tolerability, long-term compliance, and giredestrant combination therapy use; using pharmacodynamic markers for early drug activity assessment; and testing multiple dose levels during dose-escalation and -expansion phases. Data were leveraged from preclinical and phase I/II studies in metastatic and early breast cancer, as a single agent with palbociclib, to inform giredestrant dose selection.Expert opinion: Our learnings challenge the MTD paradigm in drug development, particularly in targeted therapies, and demonstrate the importance of basing dose selection on the totality of evidence, including preclinical data, and may help inform the clinical development of future targeted therapies.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"19-28"},"PeriodicalIF":4.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146085178","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

Pharmacokinetics and safety of candidate biosimilar CT-P55 versus reference secukinumab: a three-arm, randomized, double-blinded, single-dose, multicenter, Phase I study. 候选生物仿制药CTP55与参比secukinumab的药代动力学和安全性：一项三组、随机、双盲、单剂量、多中心、I期研究

IF 4.1 2区医学

Expert opinion on investigational drugs Pub Date : 2026-01-01 Epub Date: 2026-02-22 DOI: 10.1080/13543784.2026.2628208

Tomoko Hasunuma, Michio Yagi, Noboru Nakamichi, Andrew Blauvelt, Diamant Thaçi, JeeHye Suh, JungBin Cha, IIn Noh, EunKyung Lee, Kim A Papp

{"title":"Pharmacokinetics and safety of candidate biosimilar CT-P55 versus reference secukinumab: a three-arm, randomized, double-blinded, single-dose, multicenter, Phase I study.","authors":"Tomoko Hasunuma, Michio Yagi, Noboru Nakamichi, Andrew Blauvelt, Diamant Thaçi, JeeHye Suh, JungBin Cha, IIn Noh, EunKyung Lee, Kim A Papp","doi":"10.1080/13543784.2026.2628208","DOIUrl":"10.1080/13543784.2026.2628208","url":null,"abstract":"Background: This first-in-human study compared the pharmacokinetics, safety, and immunogenicity of candidate biosimilar CT-P55 to both European Union (EU)-approved and United States (US)-licensed secukinumab in healthy participants.Research design and methods: Three-arm, double-blinded, parallel-group, single-dose, Phase 1 study conducted across four centers in Japan over 22 weeks. Healthy adult males were randomized (1:1:1) to a single 150-mg subcutaneous dose of CTP55, EU-approved, or US-licensed secukinumab. Primary endpoints were area under the concentration-time curve from time zero to infinity (AUC0-inf) and maximum serum drug concentration (Cmax).Results: Baseline characteristics were comparable across groups (CT-P55 [n = 57], EU-approved secukinumab [n = 59], and US-licensed secukinumab [n = 56]). The 90% confidence intervals for the geometric least squares mean ratios of AUC0-inf and Cmax were within the equivalence margin (80-125%). Safety profiles were comparable. 218 treatment-emergent adverse events were reported for 110 (65.5%) participants; most were Grade 1/2. One serious adverse event was reported (US-licensed secukinumab group). The low immunogenic profile of CT-P55 was comparable to both reference secukinumab groups, with no neutralizing antibodies detected.Conclusions: CT-P55 exhibited equivalent pharmacokinetics as well as comparable safety and immunogenicity to both EU-approved and US-licensed secukinumab in healthy Japanese males. Generalizability may be limited beyond Asian males.Trial registration: The study is registered at Clinicaltrials.gov (NCT07054970).","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"179-188"},"PeriodicalIF":4.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146149547","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