A Phase 1b/2 Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Clinical Activity of GSK5764227 in Combination With Standard of Care (SoC) or Other Agents in Participants With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 84
- 试验地点
- 6
- 主要终点
- Number of participants with adverse events (AEs), Serious AEs (SAEs), AE of special interest (AESIs) and AEs leading to dose modifications
研究概览
简要总结
The goal of this clinical trial is to test a new medicine called GSK5764227, which delivers a toxin directly to cancer cells to destroy them while sparing healthy cells. The study will combine GSK5764227 with standard treatments to evaluate its safety, examine how the body processes it, check if it triggers any immune responses, and assess whether it can shrink or control cancer.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •Has an ECOG performance status of 0 or 1, with no deterioration in the 2 weeks before first dose.
- •Has adequate organ function.
- •Has histologically confirmed unresectable adenocarcinoma or unresectable metastatic adenocarcinoma of the colon or rectum. (Cohort A)
- •Histologically or cytologically confirmed adenocarcinoma of the prostate (Cohort B)
排除标准
- •Has a malignancy (except disease under study) that has progressed or required active treatment within the past 24 months except for basal cell or squamous cell carcinomas of the skin or in-situ carcinomas [e.g., breast, cervix, bladder] that have been resected with no evidence of disease.
- •Has had any major surgery within 28 days prior to first dose.
- •Has clinically significant bleeding symptoms or significant bleeding tendency within 1 month prior to the first dose.
- •Has serious infection within 4 weeks prior to the first dose,
- •Has untreated brain or central nervous system (CNS) metastases or brain/CNS metastases that have progressed
- •Any evidence of current interstitial lung disease (ILD) or pneumonitis OR a prior history of ILD requiring high-dose glucocorticoids or non-infectious pneumonitis requiring high-dose glucocorticoids.
- •Has a history of autoimmune disease that has required systemic treatments in the 2 years prior to screening.
- •Has received immunosuppressive agents within 30 days prior to first dose of study intervention (or requires long-term [30 days or longer]). Low-dose corticosteroids (prednisone ≤10 milligrams (mg)/day or equivalent) may be administered.
研究组 & 干预措施
Metastatic colorectal cancer (mCRC) cohort A1
干预措施: Bevacizumab (Drug)
Metastatic colorectal cancer (mCRC) cohort A1
干预措施: GSK5764227 (Drug)
Metastatic colorectal cancer (mCRC) cohort A2
干预措施: GSK5764227 (Drug)
Metastatic colorectal cancer (mCRC) cohort A2
干预措施: Bevacizumab (Drug)
Metastatic colorectal cancer (mCRC) cohort A2
干预措施: Fluorouracil (Drug)
Metastatic colorectal cancer (mCRC) cohort A2
干预措施: leucovorin (Drug)
Metastatic castration-resistant prostate cancer (mCRPC) cohort B
干预措施: GSK5764227 (Drug)
Metastatic castration-resistant prostate cancer (mCRPC) cohort B
干预措施: Enzalutamide (Drug)
结局指标
主要结局
Number of participants with adverse events (AEs), Serious AEs (SAEs), AE of special interest (AESIs) and AEs leading to dose modifications
时间窗: Up to approximately 31 weeks
Number of participants with AEs, SAEs, AESIs, and AEs leading to dose modifications by severity
时间窗: Up to approximately 31 weeks
Number of participants with clinically significant changes in Vital Signs, Body Weight, Laboratory Tests [Hematology, Clinical Chemistry, Urinalysis], Cardiac Function [ECG], and Eastern Cooperative Oncology Group (ECOG) performance status
时间窗: Up to approximately 31 weeks
Number of participants with dose limiting toxicities (DLTs)
时间窗: Up to approximately 31 weeks
次要结局
- Duration of Response (DoR)(Up to approximately 112 weeks)
- Number of participants with neutralising antibody (NAb) against GSK5764227(Up to approximately 112 weeks)
- Disease control Rate (DCR18)(Up to approximately 112 weeks)
- Plasma concentration of GSK5764227 [conjugated antibody and payload (GSK5757810)(Up to approximately 112 weeks)
- Number of participants with anti-drug antibody (ADA) against GSK5764227(Up to approximately 112 weeks)
- Objective Response Rate (ORR)(Up to approximately 112 weeks)
- Prostate-specific antigen 50 (PSA50)(Up to approximately 112 weeks)
- Titer of ADA against GSK5764227(Up to approximately 112 weeks)
- Progression free survival (PFS)(Up to approximately 112 weeks)
- Radiographic progression-free survival (rPFS)(Up to approximately 112 weeks)