A Phase 2a, Multicenter, Randomized, Open-Label Study to Assess the Efficacy, Safety, and Tolerability of RBS2418 in Combination With Tremelimumab Plus Durvalumab for Participants With Advanced Unresectable Hepatocellular Carcinoma
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 220
- 试验地点
- 4
- 主要终点
- Progression Free Survival (PFS)
研究概览
简要总结
RBS2418 is a targeted immune modulator that inhibits ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1). It is designed to promote anti-tumor immunity by preserving endogenous 2'-3' cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) from hydrolysis, thereby activating antigen-presenting cells and promoting robust T cell activation. Ideally, RBS2418 acts synergistically with CTLA-4 inhibitors, such as those in the STRIDE regimen (Tremelimumab plus Durvalumab). The hypothesis is that RBS2418 combined with STRIDE will be safe, well-tolerated, highly immunogenic, and enhance anti-tumor responses in adult participants with advanced, unresectable hepatocellular carcinoma (HCC) compared to STRIDE alone.
详细描述
In this Phase 2a study, participants must have advanced, unresectable HCC confirmed by radiology, histology or cytology. Participants must be eligible to receive the STRIDE regimen as first line therapy. Participants must have measurable disease per RECIST 1.1, an Eastern Cooperative Oncology Group (ECOG) performance score of 0, 1 or 2, and predicted life expectancy of at least 12 weeks.
Up to approximately 220 participants will be enrolled and will receive therapy as part of their respective treatment group. Participants will receive study treatment of RBS2418 at two different dose levels (200mg and 800mg) twice daily in combination with STRIDE or STRIDE alone with a treatment period consisting of 28-day cycles up to two years or until there is progressive disease, death, withdrawal, or study completion, whichever comes first.
Adverse Events (AEs) will be monitored throughout the study and graded in severity according to the guidelines outlined in the NCI CTCAE v5.0. AEs will be collected until up to 30 days after the last dose of RBS2418 or until resolution, whichever comes first. SAEs will be collected for 90 days after the last dose of RBS2418, or if the participant initiates new anti-cancer therapy, then 30 days after the RBS2418 last dose, whichever is earlier.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 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
- •At least 18 years of age on the day of signing informed consent.
- •Male and female participants with advanced, unresectable HCC who are eligible to receive STRIDE regimen as first line therapy.
- •Willing to submit a pre-treatment tissue sample (archival or fresh tissue if archival is not available).
排除标准
- •BCLC stage D disease at the time of screening or prior to first dose of RBS
- •Child-Pugh class equal or higher than B8 at the time of screening or within 7 days prior to the first dose of study treatment.
- •Eligible for curative treatments (e.g., surgical resection, liver transplantation, or local ablation).
- •Evidence of rapid progression on prior therapy resulting in rapid clinical deterioration.
研究组 & 干预措施
Arm A: RBS2418, 200mg BID, plus STRIDE
RBS2418 200 mg PO, BID in combination with STRIDE regimen
干预措施: RBS2418 (Drug)
Arm A: RBS2418, 200mg BID, plus STRIDE
RBS2418 200 mg PO, BID in combination with STRIDE regimen
干预措施: STRIDE (durvalumab + tremelimumab) (Drug)
Arm B: RBS2418, 800mg BID, plus STRIDE
RBS2418 800 mg PO, BID in combination with STRIDE regimen
干预措施: RBS2418 (Drug)
Arm B: RBS2418, 800mg BID, plus STRIDE
RBS2418 800 mg PO, BID in combination with STRIDE regimen
干预措施: STRIDE (durvalumab + tremelimumab) (Drug)
Arm C: STRIDE alone (control)
STRIDE regimen
干预措施: STRIDE (durvalumab + tremelimumab) (Drug)
结局指标
主要结局
Progression Free Survival (PFS)
时间窗: From randomization until the first radiographic documentation of objective progression or death from any cause, assessed up to 2 years.
Time in months from randomization until the first radiographic documentation of objective progression, as assessed using RECIST 1.1, or death from any cause.
次要结局
- Overall Survival (OS)(From randomization until death from any cause, assessed up to 2 years.)
- Overall Response Rate (ORR) by RECIST 1.1(From randomization to initial response, assessed up to 2 years)
- Duration of Response (DOR) by RECIST 1.1(From initial response to disease progression or death, assessed up to 2 years)
- Disease Control Rate (DCR)(From randomization to end of treatment or disease progression, assessed up to 2 years.)
- Overall Survival (OS)(From randomization until death from any cause, assessed up to 2 years.)
- Overall Response Rate (ORR) by RECIST 1.1(From randomization to initial response, assessed up to 2 years)
- Duration of Response (DOR) by RECIST 1.1(From initial response to disease progression or death, assessed up to 2 years)
- Disease Control Rate (DCR)(From randomization to end of treatment or disease progression, assessed up to 2 years.)