A Randomized, Double-Blind, Placebo-Controlled, Phase 2a Study of RBS2418 Plus Best Supportive Care (BSC) in Subjects With Advanced, Metastatic, and Progressive Colorectal Cancer
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 150
- 试验地点
- 8
- 主要终点
- Progression Free Survival
研究概览
简要总结
RBS2418 is a specific immune modulator that works through the inhibition of ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) and is designed to lead to anti-tumor immunity by protecting endogenous 2'-3'-cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) from hydrolysis and leading to the activation of antigen-presenting cells followed by T cell activation. The hypothesis is that RBS2418 versus placebo will be generally safe, well-tolerated, immunogenic, and will lead to anti-tumor responses in adult subjects for the treatment of advanced, metastatic, and progressive colorectal cancer (CRC).
详细描述
In this Phase 2a study, subjects must have failed, been unable to tolerate, or declined to take known standard-of-care (SOC) therapies. Subjects 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 greater or equal to 3 months.
Up to approximately 150 subjects will be enrolled and will receive therapy as part of their respective treatment group. Subjects will receive study treatment of RBS2418 or Placebo to Match plus Best Supportive Care with a treatment period consisting of 21-day cycles up to two years or until there is progressive disease (PD), 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 National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0. AEs will be collected until up to 30 days after the end of treatment or until resolution, whichever comes first. Serious Adverse Events (SAEs) will be collected for 90 days after the end of treatment, or if the subject initiates new anti-cancer therapy, then 30 days after the end of treatment, 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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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 subjects with advanced, metastatic, progressive CRC who have received, been ineligible for, intolerant to, or declined all approved standard of care (SOC) therapies for metastatic CRC, as per local SOC treatment regimens. Additionally, subjects must have documented PD based on two scans performed within 2 to 4 months of study initiation.
- •Have histologically or cytologically confirmed CRC diagnosis based on pathology report.
- •Willing to submit a pre-treatment tissue sample (archival, or fresh tissue if archival is not available).
排除标准
- •Any approved anti-cancer therapy including chemotherapy, targeted small molecule therapy, systemic immunotherapy, or radiation therapy within 2 weeks prior to the first dose of study treatment; or if subject has not recovered (i.e., ≤ to Grade 1 or returned to baseline level) from AEs due to a previously administered agent; the following exceptions are allowed:
- •Palliative radiotherapy for bone metastases or soft tissue lesions should be completed >7 days prior to the first dose of study treatment.
- •Hormone-replacement therapy or oral contraceptives.
- •Subjects with Grade 2 neuropathy or Grade 2 alopecia.
- •Subjects with evidence of rapid progression on prior therapy resulting in rapid clinical deterioration.
- •Malignancies other than indications open for enrollment within 3 years prior to Day 1, except for those with negligible risk of metastasis or death treated with expected curative outcome, undergoing active surveillance, or treatment-naïve for indolent tumors.
研究组 & 干预措施
Group B: EG+ (ENPP1 and cGAS positive) Placebo plus Best Supportive Care
Placebo: 2 placebo capsules, PO, BID plus Best Supportive Care
干预措施: Placebo (Drug)
Group A: EG+ [ENPP1 and cGAS(Cyclic GMP-AMP synthase) positive] RBS2418 plus Best Supportive Care
RBS2418: 200 mg (2 RBS2418 capsules), PO (by mouth), BID (twice a day) plus Best Supportive Care
干预措施: RBS2418 (Drug)
Group C: EG- (ENPP1 and/or cGAS negative) RBS2418 plus Best Supportive Care
RBS2418: 200 mg (2 RBS2418 capsules), PO, BID plus Best Supportive Care
干预措施: RBS2418 (Drug)
Group D: EG- (ENPP1 and/or cGAS negative) Placebo plus Best Supportive Care
Placebo: 2 placebo capsules, PO, BID plus Best Supportive Care
干预措施: Placebo (Drug)
结局指标
主要结局
Progression Free Survival
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 Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, or death from any cause
Overall Survival
时间窗: From randomization until death from any cause, assessed up to 2 years.
Time in months from the date of randomization to the date of death from any cause
次要结局
- Duration of Response (DOR)(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.)