Zanzalintinib (XL092): a next-generation tyrosine kinase inhibitor-comprehensive review of early safety & efficacy data.

IF 4.9 2区医学 Q1 PHARMACOLOGY & PHARMACY

Expert opinion on investigational drugs Pub Date : 2024-09-01 Epub Date: 2024-08-07 DOI:10.1080/13543784.2024.2388571

James Yu, Robin Park, Alireza Tojjari, Arezoo Sadeghipour, Ali Saeed, Anwaar Saeed

{"title":"Zanzalintinib (XL092): a next-generation tyrosine kinase inhibitor-comprehensive review of early safety & efficacy data.","authors":"James Yu, Robin Park, Alireza Tojjari, Arezoo Sadeghipour, Ali Saeed, Anwaar Saeed","doi":"10.1080/13543784.2024.2388571","DOIUrl":null,"url":null,"abstract":"Introduction: Zanzalintinib (XL092) is a next-generation anti-VEGFR-related multi-targeted TKI that exhibits immunomodulatory effects.Areas covered: This review explores preclinical and clinical data, along with the future directions associated with zanzalintinib and its combination with immune checkpoint inhibitors (ICIs).Expert opinion: In addition to its anti-VEGFR activity, zanzalintinib demonstrates potential synergistic effects with ICIs through its immunomodulatory impact, attributed to its inhibition of MET and TAM kinases. Recent preclinical studies provide compelling evidence supporting this synergistic potential. Furthermore, a recent phase 1 dose escalation study confirmed the tolerability of the zanzalintinib and anti-PDL1 combination without major safety concerns.Multiple ongoing clinical trials are investigating the combination of zanzalintinib and ICIs across various solid tumor types, including phase 3 studies for renal cell carcinoma, colorectal, and head and neck cancer. These trials aim to elucidate the therapeutic role of this new-generation TKI and ICI combination.However, the identification of reliable predictive biomarkers for the zanzalintinib and ICI combination presents significant challenges. Given the intricate nature of their mechanistic rationale and the difficulties in identifying reliable biomarkers for combined anti-angiogenesis and ICI therapies, addressing this challenge remains a priority for ongoing and future research.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"887-895"},"PeriodicalIF":4.9000,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Expert opinion on investigational drugs","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/13543784.2024.2388571","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/8/7 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}

引用次数: 0

Abstract

Introduction: Zanzalintinib (XL092) is a next-generation anti-VEGFR-related multi-targeted TKI that exhibits immunomodulatory effects.

Areas covered: This review explores preclinical and clinical data, along with the future directions associated with zanzalintinib and its combination with immune checkpoint inhibitors (ICIs).

Expert opinion: In addition to its anti-VEGFR activity, zanzalintinib demonstrates potential synergistic effects with ICIs through its immunomodulatory impact, attributed to its inhibition of MET and TAM kinases. Recent preclinical studies provide compelling evidence supporting this synergistic potential. Furthermore, a recent phase 1 dose escalation study confirmed the tolerability of the zanzalintinib and anti-PDL1 combination without major safety concerns.Multiple ongoing clinical trials are investigating the combination of zanzalintinib and ICIs across various solid tumor types, including phase 3 studies for renal cell carcinoma, colorectal, and head and neck cancer. These trials aim to elucidate the therapeutic role of this new-generation TKI and ICI combination.However, the identification of reliable predictive biomarkers for the zanzalintinib and ICI combination presents significant challenges. Given the intricate nature of their mechanistic rationale and the difficulties in identifying reliable biomarkers for combined anti-angiogenesis and ICI therapies, addressing this challenge remains a priority for ongoing and future research.

查看原文本刊更多论文

赞扎林替尼（XL092）：新一代酪氨酸激酶抑制剂--早期安全性和有效性数据的全面回顾。

简介赞扎林替尼（XL092）是新一代抗血管内皮生长因子相关多靶点 TKI，具有免疫调节作用：本综述探讨了临床前和临床数据，以及zanzalintinib及其与免疫检查点抑制剂（ICIs）联用的未来发展方向：除了抗血管内皮生长因子受体（VEGFR）活性外，赞扎林替尼还通过抑制MET和TAM激酶产生的免疫调节作用，显示出与ICIs的潜在协同效应。最近的临床前研究提供了令人信服的证据来支持这种协同潜力。此外，最近的一项 1 期剂量递增研究证实，zanzalintinib 和抗 PDL1 联合用药具有耐受性，没有重大的安全性问题。目前正在进行的多项临床试验正在研究 zanzalintinib 和 ICIs 在各种实体瘤类型中的联合用药，包括针对肾细胞癌、结直肠癌和头颈癌的 3 期研究。这些试验旨在阐明这种新一代 TKI 和 ICI 联合疗法的治疗作用。然而，为赞扎林替尼和 ICI 联合疗法确定可靠的预测性生物标志物是一项重大挑战。鉴于其机理原理错综复杂，而且很难确定抗血管生成和 ICI 联合疗法的可靠生物标志物，因此应对这一挑战仍是当前和未来研究的重点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Expert opinion on investigational drugs 医学-药学

CiteScore

10.00

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： Expert Opinion on Investigational Drugs (ISSN 1354-3784 [print], 1744-7658 [electronic]) is a MEDLINE-indexed, peer-reviewed, international journal publishing review articles and original papers on drugs in preclinical and early stage clinical development, providing expert opinion on the scope for future development. The Editors welcome: Reviews covering preclinical through to Phase II data on drugs or drug classes for specific indications, and their potential impact on future treatment strategies Drug Evaluations reviewing the clinical and pharmacological data on a particular drug Original Research papers reporting the results of clinical investigations on agents that are in Phase I and II clinical trials The audience consists of scientists, managers and decision-makers in the pharmaceutical industry, and others closely involved in R&D.