A Randomized, Open-label, Phase 2b Study to Compare the Efficacy of DSP107 in Combination With Atezolizumab Versus Fruquintinib in Patients With Advanced Microsatellite Stable Colorectal Cancer
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 90
- 试验地点
- 25
- 主要终点
- To determine Median overall survival (mOS) in participants treated with the combination of DSP107 and atezolizumab versus fruquintinib.
研究概览
简要总结
This clinical study is testing whether a new combination of medicines (DSP107 and atezolizumab) is more effective and safer than an existing treatment (fruquintinib) for people with advanced colorectal cancer that is microsatellite stable (MSS). Participants will be randomly assigned to receive one of the two treatments, and researchers will monitor how well the cancer responds, how safe the treatments are, and how the body processes them. The study hopes to show that the new combination can improve outcomes for patients with this type of colorectal cancer.
详细描述
This Phase 2b, randomized, open-label, multicenter study will enroll participants with advanced MSS or mismatch repair-proficient (pMMR) colorectal cancer who have progressed on, or shown intolerance to, standard therapies, including fluoropyrimidine, irinotecan, oxaliplatin, trifluridine/tipiracil (Lonsurf), bevacizumab, and epidermal growth factor receptor (EGFR) inhibitors if RAS wild-type. Participants with BRAF V600E mutation, HER2 amplification/overexpression, KRAS G12C mutation, RET fusion, or NTRK fusion may also have received one prior targeted therapy. Prior treatment with fruquintinib or regorafenib is not allowed.
Participants will be randomized 1:1 into two arms:
Group A (Experimental): DSP107 10 mg/kg intravenously on Days 1, 8, and 15 of each 28-day cycle, administered after atezolizumab 1680 mg IV on Day 1 of each cycle. DSP107 infusion may be shortened after initial tolerance. Atezolizumab infusion may be shortened from 60 to 30 minutes if well tolerated.
Group B (Active Comparator): Fruquintinib 5 mg orally once daily on Days 1-21 of each 28-day cycle, with dosing diaries maintained by participants.
Total duration of study participation for each participant will vary based on factors including treatment tolerability, disease progression and other study discontinuation criteria.
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
- •Are ≥ 18 years of age with a life expectancy of > 3 months.
- •Participants with histologically confirmed, inoperable, MSS and/or pMMR CRC which has progressed to, or is intolerant to, specified therapies (and has received prior treatment with no more than 3 lines of therapy).
- •Measurable disease per RECIST v1.1.
排除标准
- •Central nervous system (CNS) metastases unless stable 2 months post definitive therapy with steroids.
- •Unresolved AEs of Grade 2 or higher from prior anticancer therapy.
- •Past or current history of autoimmune disease or immune deficiency.
- •History of other malignancy within 3 years of first study treatment cycle.
- •Current or recent treatment with certain therapies including specified anticancer treatments, modulators of CYP3A4 and immunomodulating therapies (prior treatment with CPIs is not exclusory).
- •Known allergy or hypersensitivity to any of the test compounds, materials, or contraindication to test product.
- •Clinically significant abnormal laboratory safety tests.
研究组 & 干预措施
Fruquintinib
Participants will receive fruquintinib orally in 28-day cycles, for up to 24 cycles (96 weeks), or until disease progression, unacceptable toxicity, or study withdrawal.
干预措施: Fruquintinib (Drug)
DSP107 in combination with Atezolizumab
DSP107 10 mg/kg IV on Days 1, 8, and 15 of each 28-day cycle. Atezolizumab 1680 mg IV on Day 1 of each 28-day cycle.
干预措施: DSP107 + Atezolizumab (Drug)
结局指标
主要结局
To determine Median overall survival (mOS) in participants treated with the combination of DSP107 and atezolizumab versus fruquintinib.
时间窗: From Day 1 until date of death from any cause assessed up to 2 years
Median Overall Survival (mOS) will be estimated using Kaplan-Meier methodology as the median time from the start of study treatment to the last known date a participant was alive. Censoring rules will be applied for participants without an event at the time of analysis, and 95% confidence intervals for mOS will be provided.
次要结局
- Incidence and severity of adverse events (AEs)(From Screening to Follow-up (30 to 90 Days Post IP))
- Changes in 12-lead ECG parameters(From Baseline through to end of treatment visit, an average of 6 months)
- Change in Overall Survival (OS)(From randomization through study participation, with survival follow-up for up to 5 years in the DSP107_SFU study.)
- Change from Baseline in Quality of Life (QoL)(From Baseline through to end of treatment visit, an average of 6 months)
- Change from Baseline in Systolic and Diastolic Blood Pressure(From Baseline through to end of treatment visit, an average of 6 months)
- Change from Baseline in Pulse Rate(From Baseline through to end of treatment visit, an average of 6 months)
- To evaluate the immunogenicity of DSP107 when administered in combination with atezolizumab.(From Baseline through to end of treatment visit, an average of 6 months)