This registration study assessed clinical outcomes of TQ-B3525, the dual phosphatidylinositol-3-kinase (PI3K) α/δ inhibitor, in relapsed and/or refractory follicular lymphoma (R/R FL). This phase II study (ClinicalTrials.gov NCT04324879. Registered March 27, 2020) comprised run-in stage and stage 2. R/R FL patients after ≥2 lines therapies received oral 20 mg TQ-B3525 once daily in a 28-day cycle until intolerable toxicity or disease progression. Primary endpoint was independent review committee (IRC)-assessed objective response rate (ORR). Based on results (ORR, 88.0%; duration of response [DOR], 11.8 months; progression-free survival [PFS], 12.0 months) in 25 patients at run-in stage, second stage study was initiated and included 82 patients for efficacy/safety analysis. Patients received prior-line (median, 3) therapies, with 56.1% refractory to previous last therapies; 73.2% experienced POD24 at baseline. At stage 2, ORR was 86.6% (71/82; 95% CI, 77.3–93.1%), with 28 (34.2%) complete responses. Disease control rate was 95.1% due to 7 (8.5%) stable diseases. Median time to response was 1.8 months. Among 71 responders, median DOR was not reached; 18-month DOR rate was 51.6%. with median follow-up of 13.3 months, median PFS was 18.5 (95% CI, 10.2-not estimable) months. Median overall survival (OS) was not reached by cutoff date; 24-month OS rate was estimated as 86.1%. Response rates and survival data were consistent across all subgroups. Grade 3 or higher treatment-related adverse events were observed in 63 (76.8%) cases, with neutropenia (22.0%), hyperglycemia (19.5%), and diarrhea (13.4%) being common. TQ-B3525 showed favorable efficacy and safety for R/R FL patients after ≥2 lines prior therapies.

这项注册研究评估了 TQ-B3525（双重磷脂酰肌醇 3 激酶 (PI3K) α/δ 抑制剂）治疗复发性和/或难治性滤泡性淋巴瘤 (R/R FL) 的临床结果。这项 II 期研究（ClinicalTrials.gov NCT04324879。注册于 2020 年 3 月 27 日）包括磨合阶段和第 2 阶段。接受≥2 种疗法后的 R/R FL 患者在 28 天的周期中每天一次口服 20 mg TQ-B3525直至出现无法忍受的毒性或疾病进展。主要终点是独立审查委员会 (IRC) 评估的客观缓解率 (ORR)。根据 25 名患者在磨合阶段的结果（ORR，88.0%；缓解持续时间 [DOR]，11.8 个月；无进展生存期 [PFS]，12.0 个月），启动了第二阶段研究，纳入了 82 名患者以评估疗效/安全分析。患者接受过既往治疗（中位数为 3 次），其中 56.1% 对之前的最后一次治疗无效； 73.2% 的人在基线时经历过 POD24。在第 2 阶段，ORR 为 86.6%（71/82；95% CI，77.3-93.1%），其中 28 例（34.2%）完全缓解。疾病稳定7例（8.5%），疾病控制率为95.1%。中位响应时间为 1.8 个月。在 71 名响应者中，未达到中位 DOR； 18个月的DOR率为51.6%。中位随访时间为 13.3 个月，中位 PFS 为 18.5 个月（95% CI，10.2 - 不可估计）。截止日期尚未达到中位总生存期 (OS)； 24 个月 OS 率估计为 86.1%。所有亚组的缓解率和生存数据均一致。 63 例 (76.8%) 病例中观察到 3 级或以上治疗相关不良事件，其中中性粒细胞减少 (22.0%)、高血糖 (19.5%) 和腹泻 (13.4%) 较常见。 TQ-B3525 在 ≥2 线既往治疗后对 R/R FL 患者显示出良好的疗效和安全性。