放射治疗是非小细胞肺癌 (NSCLC) 标准治疗方案的一部分。尽管放射治疗是管理 NSCLC 的有效工具，但它可能与重要的剂量限制毒性相关。这些毒性可能导致治疗中断或提前终止，加重临床结果，并降低患者生活质量。基于对正常组织放射保护的临床前效果评估，我们评估了 NSCLC 患者中 BIO 300 口服混悬液 (BIO 300；合成异黄酮纳米悬浮液) 的临床效用。在这个多中心、开放标签、单臂、升级剂量的 1b/2a 期研究中，我们招募了刚诊断为 II-IV 期 NSCLC 并计划进行 60-70/1.8-2.0Gy 放射治疗和同时每周紫杉醇/卡铂化疗的患者。口服 BIO 300 (队 1，500 mg/天；队 2，1000 mg/天；队 3，1500 mg/天) 在开始同步放化疗前 2-7 天开始自行每日一次，并持续到放射治疗结束。主要终点是 BIO 300 引起的急性剂量限制毒性。次要结果包括药代动力学、药效学、整体毒性配置文件、生活质量、局部缓解率和生存率。共有 21 名参与者入组。未报告剂量限制毒性。BIO 300 剂量并未改变化疗的药代动力学。不良事件与剂量无关，BIO 300 相关的不良事件 (N = 11) 全部为轻至中度 (1 级，N = 9；2 级，N = 2)，主要为胃肠道相关 (N = 7)。观察到血清 TGFβ1 水平在不同队别中存在剂量依赖的下降。基于安全性分析，BIO 300 的最大耐受剂量未达到。患者报告的生活质量和体重在整个研究期间基本稳定。没有患者出现疾病进展作为最佳整体反应，实现了 65% 的肿瘤缓解率 (完全缓解率 20%)。低毒性率、药效学结果和肿瘤缓解率的支持下，支持进一步研究 BIO 300 作为有效的放射保护剂。版权所有 © 2023。由 Elsevier Inc. 发布。

Radiotherapy is part of the standard treatment regimen for non-small cell lung cancer (NSCLC). While radiotherapy is an effective tool to manage NSCLC, it can be associated with significant dose-limiting toxicities. These toxicities can lead to treatment interruption or early termination, worsening clinical outcomes, in addition to reductions in patient quality of life. Based on preclinical efficacy for radioprotection of normal tissues, we evaluated the clinical utility of BIO 300 Oral Suspension (BIO 300; synthetic genistein nanosuspension) in patients with NSCLC.In this multicenter, open-label, single-arm, ascending dose phase 1b/2a study, patients were enrolled with newly diagnosed stage II-IV NSCLC planned for 60-70/1.8-2.0Gy radiotherapy and concurrent weekly paclitaxel/carboplatin. Oral BIO 300 (cohort 1, 500 mg/day; cohort 2, 1000 mg/day; cohort 3, 1500 mg/day) was self-administered once-daily starting 2-7 days before initiating concurrent chemoradiotherapy and continued until the end of radiotherapy. The primary endpoint was acute dose-limiting toxicities attributable to BIO 300. Secondary outcomes included pharmacokinetics, pharmacodynamics, overall toxicity profile, quality of life, local response rate and survival.Twenty-one participants were enrolled. No dose-limiting toxicities were reported. BIO 300 dosing did not alter chemotherapy pharmacokinetics. Adverse events were not dose-dependent, and those attributable to BIO 300 (N=11) were all mild to moderate in severity (grade 1, N=9; grade 2, N=2) and predominantly gastrointestinal (N=7). A dose-dependent decrease in serum TGFβ1 levels was observed across cohorts. Based on safety analysis, the maximum tolerated dose of BIO 300 was not met. Patient reported quality of life and weight were largely stable throughout the study period. No patient had progression as their best overall response, and a 65% tumor response rate was achieved (20% complete response rate).The low toxicity rates, along with the pharmacodynamic results and tumor response rates, support further investigation of BIO 300 as an effective radioprotector.Copyright © 2023. Published by Elsevier Inc.