Identification of Innovative Biomarkers to Predict Outcomes in Hepatocellular Carcinoma Treated With Tremelimumab and Durvalumab
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 120
- 试验地点
- 17
- 主要终点
- real-word overall survival
研究概览
简要总结
Several cancer immunotherapies that target the PD-L1/PD-1 pathway (i.e., checkpoint inhibitors) show promising clinical activity in patients with HCC. In particular, atezolizumab selectively targets PD-L1 to prevent interaction with receptors PD-1 and B7-1, thus reversing T-cell suppression. Moreover, atezolizumab in combination with bevacizumab, a monoclonal antibody that targets VEGF and inhibits angiogenesis, is associated with an objective response rate of 27.3% (Cheng et al. 2021; Finn et al. 2020). This tumor response has led to FDA (Food and Drug Administration) and EMA (European Medicines Agency) approvals, in first-line treatment in unresectable HCC.
Combinations studies evaluating anti-CTLA4 and anti-PD1/PDL1 antibodies displayed greater benefits (Abou-Alfa et al. 2022). In the Phase 3 HIMALAYA study (NCT03298451) in uHCC, a single priming dose of tremelimumab (anti-CTLA-4) plus durvalumab (anti-PD-L1) in the STRIDE (Single Tremelimumab Regular Interval Durvalumab) regimen significantly improved OS versus sorafenib; durvalumab monotherapy was noninferior to sorafenib for OS.
In the HIMALAYA study, STRIDE regimen induced long term survival (defined as the absence of progression above 36 months following inclusion) in 103 out of the 393 patients exposed to this strategy (26%).
The identification of biomarkers allowing the prediction of immunotherapy efficacy in HCC is still an unmet medical need.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed informed consent
- •Histologically confirmed hepatocellular carcinoma
- •Locally advanced, metastatic, or unresectable disease
- •Patient who had not previously received systemic anti-cancer treatment and are eligible to STRIDE therapy according to investigator decision in routine care and who have no contraindications to STRIDE treatment according to approved product label.
- •Measurable disease defined according to RECIST v1.1 guidelines (Note: Previously irradiated lesions can be considered as measurable disease only if disease progression has been unequivocally documented at that site since radiation.)
- •Age ≥ 18 years
- •Patient affiliated to or beneficiary of French social security system
- •Ability to comply with the study protocol, in the Investigator's judgment.
排除标准
- •Patients previously exposed to anti-tumor immunotherapy as anti-PD-1, anti-PD-L1, or anti-CTLA4 agent or any immune therapy.
- •Patient with any medical or psychiatric condition or disease, which would make the patient inappropriate for entry into this study
- •Patient under guardianship, curatorship or under the protection of justice
研究组 & 干预措施
Blood sample
干预措施: blood sample (Other)
结局指标
主要结局
real-word overall survival
时间窗: through study completion, up to a maximum of 24 months after the inclusion of the last patient
defined as the delay from the date of treatment initiation to death from any cause
次要结局
- real-word progression-free-survival(through study completion, up to a maximum of 24 months after the inclusion of the last patient)
- Objective Response Rate (ORR)(through study completion, up to a maximum of 24 months after the inclusion of the last patient)
- Disease control rate (DCR)(through study completion, up to a maximum of 24 months after the inclusion of the last patient)