TPS488
Background:
Treatment with PD-1/programmed death-ligand 1 (PD-L1) inhibitors and anti-angiogenic agents has demonstrated significant survival improvements in patients with untreated HCC. T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) is a co-inhibitory immune checkpoint receptor upregulated on T cells and natural killer cells in multiple solid tumors. OCI is a novel, humanized mAb that binds TIGIT with high specificity and affinity, blocking interaction with its ligands on tumor cells. TIS is an anti-PD-1 mAb that has demonstrated clinical activity in patients with previously treated, unresectable HCC (NCT03419897). BAT1706 is a similar biological product to the anti-angiogenic agent bevacizumab. OCI combined with TIS and BAT1706 could further enhance both anti-angiogenic and anti-PD-1 therapies for patients with HCC.
Methods:
AdvanTIG-206 is a phase 2, randomized, open-label clinical study (NCT04948697). Patients aged ≥ 18 years with histologically confirmed advanced HCC that is not amenable to a curative treatment approach are eligible. Patients must have a Child-Pugh A score, ECOG PS ≤ 1, and have received no prior systemic therapy for HCC. Approximately 90 patients will be randomized 2:1 to OCI 900 mg combined with TIS 200 mg plus BAT1706 15 mg/kg (Arm A) or TIS 200 mg plus BAT1706 15 mg/kg (Arm B), all administered intravenously (once every 3 weeks [Q3W]). The primary endpoint is investigator-assessed objective response rate per RECIST v1.1. Radiological assessment of tumor response status will be performed Q6W for the first 48 weeks and Q12W thereafter. Secondary endpoints include duration of response, time to response, disease control rate, clinical benefit rate, and progression-free survival (all investigator-assessed overall survival), safety, pharmacokinetics, and immunogenicity. Study enrollment is ongoing. Clinical trial information: NCT04948697.
中文翻译：
TPS488
背景：
使用 PD-1/程序性死亡配体 1 (PD-L1) 抑制剂和抗血管生成剂治疗已证明未经治疗的 HCC 患者的生存率显着提高。T 细胞免疫球蛋白和免疫受体酪氨酸抑制基序结构域 (TIGIT) 是一种在多个实体瘤中的 T 细胞和自然杀伤细胞上上调的共抑制免疫检查点受体。OCI 是一种新型的人源化 mAb，它以高特异性和亲和力结合 TIGIT，阻断与其配体在肿瘤细胞上的相互作用。TIS 是一种抗 PD-1 mAb，已在先前治疗的不可切除 HCC 患者中显示出临床活性 (NCT03419897)。BAT1706 是一种与抗血管生成剂贝伐单抗类似的生物制品。OCI 联合 TIS 和 BAT1706 可以进一步增强 HCC 患者的抗血管生成和抗 PD-1 治疗。
方法：
AdvanTIG-206是一项2期、随机、开放标签的临床研究（NCT04948697）。年龄 ≥ 18 岁且经组织学证实为晚期 HCC 且不适合根治性治疗方法的患者符合条件。患者必须具有 Child-Pugh A 评分，ECOG PS ≤ 1，并且之前未接受过针对 HCC 的全身治疗。大约 90 名患者将按 2:1 随机分配至 OCI 900 mg 联合 TIS 200 mg 加 BAT1706 15 mg/kg (Arm A) 或 TIS 200 mg 加 BAT1706 15 mg/kg (Arm B)，全部静脉给药（每 3 次周 [Q3W]）。主要终点是研究者根据 RECIST v1.1 评估的客观反应率。肿瘤反应状态的放射学评估将在前 48 周每 6 周进行，之后每 12 周进行。次要终点包括反应持续时间、反应时间、疾病控制率、临床受益率、和无进展生存期（所有研究者评估的总生存期）、安全性、药代动力学和免疫原性。研究招生正在进行中。临床试验资料：NCT04948697。
