AdvanTIG-105：一项评估抗 TIGIT 单克隆抗体ociperlimab 联合替雷利珠单抗治疗晚期实体瘤患者的 I 期剂量递增研究。

BACKGROUND: Ociperlimab, a novel, humanized monoclonal antibody (mAb), binds to T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains (TIGIT) with high affinity and specificity. Tislelizumab is an anti-programmed cell death protein 1 mAb. We report results from a phase I, first-in-human, dose escalation study evaluating the safety, pharmacokinetics (PK), and preliminary antitumor activity of ociperlimab plus tislelizumab in patients with advanced solid tumors. METHODS: Eligible patients previously treated with standard systemic therapy, or for whom treatment was not available or tolerated, received ociperlimab intravenously on Cycle (C) 1 Day (D) 1 and tislelizumab 200 mg intravenously on C1 D8. If tolerated, patients received ociperlimab plus tislelizumab 200 mg sequentially on D29 and every 3 weeks (Q3W) thereafter until discontinuation. Dose escalation for ociperlimab was planned with four dose levels (50 mg, 150 mg, 450 mg, and 900 mg) according to a 3+3 design. An additional dose level of ociperlimab 1800 mg was also assessed. Primary endpoints were safety, determination of the maximum tolerated (or administered) dose, and the recommended phase II dose (RP2D). Secondary endpoints included overall response rate (ORR), duration of response (DoR), disease control rate (DCR) (Response Evaluation Criteria in Solid Tumors version 1.1), PK, and biomarker analysis. RESULTS: At data cut-off (September 29, 2022), 32 patients had received ≥1 dose of ociperlimab plus tislelizumab 200 mg Q3W. The maximum administered dose was ociperlimab 1800 mg plus tislelizumab 200 mg Q3W. The median age of enrolled patients was 59.5 years (range: 31-79). Most patients (96.9%) experienced ≥1 treatment-emergent adverse event (TEAE); 62.5% of patients experienced ≥grade 3 TEAEs and 50.0% of patients experienced serious TEAEs. No dose limiting toxicity events were reported. The maximum tolerated dose was not reached. The RP2D was ociperlimab 900 mg plus tislelizumab 200 mg Q3W. Overall, ORR was 10.0%, median DoR was 3.6 months, and DCR was 50.0%. CONCLUSIONS: Ociperlimab plus tislelizumab was well tolerated in patients with advanced solid tumors, and preliminary antitumor activity was observed with 450 mg, 900 mg, and 1800 mg ociperlimab. Phase II/III trials of ociperlimab 900 mg plus tislelizumab 200 mg Q3W are underway in a range of solid tumors. TRIAL REGISTRATION NUMBER: NCT04047862.

背景：Ociperlimab 是一种新型的、人源化的单克隆抗体（mAb），与 T 细胞免疫受体具有免疫球蛋白和免疫受体酪氨酸抑制基序域（TIGIT）具有高亲和力和特异性。Tislelizumab 是一种抗程序性细胞死亡蛋白 1 mAb。我们报告了一项 I 期、首次人体、剂量递增研究的结果，该研究评估了在先前接受过标准系统治疗的晚期实体瘤患者或无法接受或耐受治疗的患者中，ociperlimab 联合 tislelizumab 的安全性、药代动力学（PK）和初步抗肿瘤活性。方法：符合条件的患者先前接受过标准系统治疗，或治疗不可用或不耐受，在第 1 周期（C）第 1 天（D）1 天静脉注射 ociperlimab，第 1 周期 C1 D8 天静脉注射 tislelizumab 200mg。如果耐受，患者在第 29 天和之后每 3 周（Q3W）接受 ociperlimab 加 tislelizumab 200mg 序贯治疗，直到停药。ociperlimab 的剂量递增计划为四个剂量水平（50mg、150mg、450mg 和 900mg），根据 3+3 设计。还评估了 ociperlimab 1800mg 的额外剂量水平。主要终点是安全性、确定最大耐受（或给予）剂量和推荐的 II 期剂量（RP2D）。次要终点包括总缓解率（ORR）、缓解持续时间（DoR）、疾病控制率（DCR）（实体瘤反应评估标准 1.1 版）、PK 和生物标志物分析。结果：在数据截止日期（2022 年 9 月 29 日），32 名患者接受了≥1 剂 ociperlimab 加 tislelizumab 200mg Q3W。最大给药剂量为 ociperlimab 1800mg 加 tislelizumab 200mg Q3W。入组患者的中位年龄为 59.5 岁（范围：31-79 岁）。大多数患者（96.9%）经历了≥1 次治疗后出现的不良事件（TEAE）；62.5%的患者出现≥3 级 TEAE，50.0%的患者出现严重的 TEAE。没有报告剂量限制毒性事件。未达到最大耐受剂量。RP2D 为 ociperlimab 900mg 加 tislelizumab 200mg Q3W。总的来说，ORR 为 10.0%，中位 DoR 为 3.6 个月，DCR 为 50.0%。结论：ociperlimab 联合 tislelizumab 在晚期实体瘤患者中耐受性良好，并观察到 450mg、900mg 和 1800mg ociperlimab 有初步抗肿瘤活性。ociperlimab 900mg 联合 tislelizumab 200mg Q3W 的 II/III 期临床试验正在多种实体瘤中进行。试验注册：NCT04047862。

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新学期，新优惠

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AdvanTIG-105: a phase I dose escalation study of the anti-TIGIT monoclonal antibody ociperlimab in combination with tislelizumab in patients with advanced solid tumors.

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