A Phase Ib/II Study to Evaluate the Safety, Tolerability, and Efficacy of SYS6090 in Combination With Other Therapies in Participants With Advanced Coloretal Cancer
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 260
- 试验地点
- 1
- 主要终点
- Recommended Phase 2 Dose (RP2D), Safety and Tolerability
研究概览
简要总结
This study constitutes an open-label, multi-cohort, multi-center Phase Ib/II clinical study, developed to assess the safety, tolerability, and therapeutic efficacy of SYS6090 injection when administered in combination with bevacizumab, or in triple combination with bevacizumab and chemotherapy, among patients diagnosed with advanced colorectal cancer.
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
- •*Eligibility Criteria:
- •Inclusion Criteria:
- •Subjects must be ≥18 years of age.
- •Histologically or cytologically confirmed unresectable advanced or metastatic colorectal cancer with pMMR/MSS status, assigned to corresponding cohorts as follows:
- •Cohort 1 (2L/3L) of Phase Ib & Phase II: Subjects must have disease progression after no more than 2 lines of standard systemic therapy (prior regimens must contain fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy); tumor tissue confirmed as pMMR by IHC or MSS by NGS/PCR; Cohort 2 (1L) of Phase Ib & Phase II: Subjects have received no prior systemic anti-tumor therapy for advanced disease; tumor tissue confirmed as pMMR by IHC or MSS by NGS/PCR.
- •At least one extracranial measurable lesion at baseline according to RECIST 1.1 criteria.
- •Eastern Cooperative Oncology Group performance status of 0 or
- •Expected survival ≥ 3 months.
- •Has protocol-defined adequate organ and bone marrow function.
排除标准
- •Subjects with clinically active central nervous system metastases;
- •with a history of other primary malignant tumors within 5 years before administration;
- •Subjects assigned to Cohort 1 who have received prior regorafenib treatment.;
- •Prior documented interstitial lung disease (ILD)/ pneumonitis that required steroids, current ILD/ pneumonitis, or suspected ILD/ pneumonitis that cannot be ruled out by imaging at screening;
- •Uncontrolled or significant cardiovascular disease;
- •Clinically uncontrolled pleural effusion, ascites or pericardial effusion;
- •Has unresolved toxicities from previous anticancer therapy, defined as toxicities not yet resolved to Grade ≤ 1 or baseline .
研究组 & 干预措施
Ib-Randomized Arm 1
Enrolled Subjects will be randomized to receive SYS6090 at the fixed dose level A in combination with bevacizumab. The exact dose magnitude and administration frequency of SYS6090 are temporarily undisclosed to protect pending patent information, with full dosing details archived in platform backend for regulatory review only.
干预措施: SYS6090 (Fixed Dose Level A) + bevacizumab (Drug)
Ib-Randomized Arm 2
Enrolled Subjects will be randomized to receive SYS6090 at the fixed dose level B in combination with bevacizumab. The exact dose magnitude and administration frequency of SYS6090 are temporarily undisclosed to protect pending patent information, with full dosing details archived in platform backend for regulatory review only.
干预措施: SYS6090 (Fixed Dose Level B ) + bevacizumab (Drug)
II-Cohort 1- Randomized Arm A
Enrolled Subjects will be randomized to receive SYS6090 at RP2D combined with bevacizumab and mFOLFOX6
干预措施: SYS6090 RP2D + bevacizumab +mFOLFOX6 (Drug)
II-Cohort 1- Randomized Arm B
Enrolled Subjects will be randomized to receive SYS6090 at RP2D combined with bevacizumab
干预措施: SYS6090 RP2D + bevacizumab (Drug)
II-Cohort 2- Randomized Arm D
Enrolled Subjects will be randomized to receive SYS6090 at RP2D combined with bevacizumab and FOLFOXIRI
干预措施: SYS6090 PR2D+ bevacizumab + FOLFOXIRI (Drug)
II-Cohort 2- Randomized Arm E
Enrolled Subjects will be randomized to receive bevacizumab combined with FOLFOXIRI
干预措施: bevacizumab + FOLFOXIRI (Drug)
II-Cohort 1- Randomized Arm C
Enrolled Subjects will be randomized to receive regorafenib
干预措施: Regorafenib (Drug)
结局指标
主要结局
Recommended Phase 2 Dose (RP2D), Safety and Tolerability
时间窗: up to approximately 3 years after the first enrollment
RP2D of SYS6090 combination therapy,Safety and tolerability are evaluated via incidence and severity of all Adverse Events (AEs) and Serious Adverse Events (SAEs) graded per NCI-CTCAE version 6.0, including abnormal laboratory tests, ECG parameters and vital signs from screening through end of safety follow-up.
Objective Response Rate (ORR) assessed per RECIST v1.1
时间窗: up to approximately 3 years after the first enrollment
ORR per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) assessed by investigator was defined as the percentage of participants with at least one visit confirmed complete response (CR) or partial response (PR), for all cohorts in Phase Ib and Cohort 1 of Phase II expansion stage.
Progression-Free Survival (PFS) assessed per RECIST v1.1
时间窗: up to approximately 3 years after the first enrollment
PFS per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) assessed by investigator was defined as the time from the date of randomization or first study treatment until the date of confirmed progressive disease (PD), or death by any cause in the absence of progression, regardless of whether the participant withdrew from study therapy or received another anticancer therapy prior to progression, for Cohort 2 of Phase II expansion stage.
次要结局
未报告次要终点