Department of Oncology, Tianjin Union Medical Center of Nankai University, Tianjin, 300121, PR China.
The Institute of Translational Medicine, Tianjin Union Medical Center of Nankai University, Tianjin, 300121, PR China.
Signal Transduct Target Ther. 2024 Apr 17;9(1):99. doi: 10.1038/s41392-024-01798-0.
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）在复发和/或难治性滤泡淋巴瘤（R/R FL）患者中的临床结局。这项 II 期研究（ClinicalTrials.gov NCT04324879，于 2020 年 3 月 27 日注册）包括入组阶段和 2 期。≥2 线治疗后复发或难治的 R/R FL 患者接受每日口服 TQ-B3525 20mg，28 天为一个周期，直至出现不可耐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）。根据入组阶段 25 例患者的结果（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），启动了第二期研究，共纳入 82 例患者进行疗效/安全性分析。患者接受了既往线（中位数，3 线）治疗，其中 56.1%对前序治疗难治；基线时 73.2%患者存在 POD24。在第 2 阶段，ORR 为 86.6%（71/82；95%CI，77.3-93.1%），其中 28 例（34.2%）为完全缓解。由于 7 例（8.5%）患者疾病稳定，疾病控制率为 95.1%。中位缓解时间为 1.8 个月。在 71 例缓解者中，中位 DOR 尚未达到；18 个月 DOR 率为 51.6%。中位随访 13.3 个月时，中位 PFS 为 18.5 个月（95%CI，10.2-无法评估）。截止日期时未达到中位总生存期（OS）；24 个月 OS 率估计为 86.1%。各亚组的缓解率和生存数据一致。63 例（76.8%）患者发生 3 级或更高级别的治疗相关不良事件，其中中性粒细胞减少症（22.0%）、高血糖症（19.5%）和腹泻（13.4%）较为常见。TQ-B3525 为≥2 线治疗后复发或难治的 FL 患者带来了良好的疗效和安全性。
