A Phase 1, Open-Label, Two-Part (Dose Escalation and Expansion) Study of DEM301 in Participants With Select Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 60
- 主要终点
- Part A: Incidence of Dose-Limiting Toxicities (DLTs)
研究概览
简要总结
This is a first-in-human Phase 1 study of DEM301 in adults with previously treated advanced metastatic colorectal cancer. DEM301 is an investigational antibody-drug conjugate. The study will evaluate the safety and tolerability of DEM301, identify doses for further study, and assess how the drug behaves in the body and whether it shows signs of activity against the cancer.
详细描述
This is a Phase 1, multicenter, open-label study of DEM301 in participants with previously treated advanced metastatic colorectal cancer. The study has two parts: Dose Escalation, and Dose Expansion.
Dose Escalation will evaluate the safety and tolerability of DEM301 and identify one or more recommended doses for further study. Dose Expansion will further evaluate DEM301 at the selected dose or doses.
The study will also assess preliminary antitumor activity, pharmacokinetics, immunogenicity, pharmacodynamic effects, and exploratory biomarkers. Approximately 60 participants are planned.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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
- •Age ≥18 years.
- •Participants must have documented advanced (metastatic or unresectable) colorectal cancer that has progressed on or after prior standard-of-care treatment and must have received, or been unable to receive, applicable standard therapies as defined in the protocol.
- •Life expectancy ≥12 weeks.
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-
- •Have at least 1 measurable lesion at baseline suitable for repeat imaging evaluation by RECIST v1.
- •Adequate bone marrow, liver, kidney, and coagulation function per protocol requirements.
- •Agree to provide adequate tumor tissue for protocol-required biomarker assessment. Participants in designated cohorts must be willing to provide fresh tumor biopsies, unless medically contraindicated.
- •Female participants must not be pregnant or breastfeeding. Male and female participants must comply with protocol-defined reproductive and contraception requirements.
- •Have suitable venous access for study treatment and required blood sampling.
- •Be willing and able to comply with study assessments, schedule, and restrictions.
- •Written informed consent must be obtained before any study-related procedures are performed.
排除标准
- •Prior treatment with certain antibody-drug conjugates, as defined in the protocol. Protocol-defined exceptions may apply.
- •Recent anticancer therapy, investigational treatment, major surgery, or radiation therapy within the protocol-defined washout periods.
- •Ongoing clinically significant toxicity from prior therapy that has not recovered to the protocol-required level.
- •Active central nervous system (CNS) metastases or suspected or confirmed leptomeningeal disease. Participants with treated and stable brain metastases may be eligible.
- •Recent thromboembolic event or clinically significant cardiovascular disease.
- •Active or uncontrolled infection, including active viral hepatitis, unless protocol-defined eligibility criteria are met.
- •Known HIV infection or AIDS-related illness unless protocol-defined eligibility criteria are met.
- •History of or current drug-induced interstitial lung disease/pneumonitis, suspected interstitial lung disease (ILD)/pneumonitis, or other severe or uncontrolled chronic pulmonary disease.
- •Another malignancy within the previous 3 years, except certain malignancies with a low risk of recurrence.
- •Recent systemic corticosteroid therapy or live attenuated vaccination, except as permitted by the protocol.
- •Known hypersensitivity to DEM301 or its ingredients, or any serious medical, psychiatric, or other condition that, in the Investigator's opinion, could affect participant safety, study participation, or interpretation of study results.
研究组 & 干预措施
Dose Escalation
Participants will receive DEM301 in sequential Dose Escalation cohorts to evaluate safety and identify doses for further study.
干预措施: DEM301 (Drug)
Dose Expansion
Participants will receive DEM301 at a recommended dose selected based on data from Dose Escalation.
干预措施: DEM301 (Drug)
结局指标
主要结局
Part A: Incidence of Dose-Limiting Toxicities (DLTs)
时间窗: 21 Days
Incidence of DLTs in DLT-evaluable participants enrolled in Part A.
Part A and Part B: Incidence of Adverse Events (AEs)
时间窗: From first dose through 30 days after the last dose, up to approximately 24 months
Incidence of AEs, including events requiring dose interruption or discontinuation, in participants enrolled in Part A and Part B.
Part A and Part B: Incidence of Serious Adverse Events (SAEs)
时间窗: From signing informed consent through 30 days after the last dose, up to approximately 24 months
Incidence of SAEs in participants enrolled in Part A and Part B. Related SAEs occurring after the End of Treatment visit will also be reported according to the protocol.
Incidence of Dose-Limiting Toxicities (DLTs)
时间窗: 21 Days
Incidence of DLTs in DLT-evaluable participants enrolled in Dose Escalation.
Incidence of Adverse Events (AEs)
时间窗: From first dose through 30 days after the last dose, up to approximately 24 months
Incidence of AEs, including events requiring dose interruption or discontinuation, in participants enrolled in Dose Escalation and Dose Expansion.
Incidence of Serious Adverse Events (SAEs)
时间窗: From signing informed consent through 30 days after the last dose, up to approximately 24 months
Incidence of SAEs in participants enrolled in Dose Escalation and Dose Expansion. Related SAEs occurring after the End of Treatment visit will also be reported according to the protocol.
次要结局
- Part A: Maximum Tolerated Dose (MTD) of DEM301, if Applicable(At completion of Part A, approximately 12 months)
- Part A: Recommended Dose(s) for Expansion (RDEs) of DEM301(At completion of Part A, approximately 12 months)
- Part A and Part B: Objective Response Rate (ORR) at 12 Weeks(12 weeks)
- Part A and Part B: Duration of Response (DoR)(Up to approximately 24 months)
- Title: Part A and Part B: Disease Control Rate (DCR) at 12 Weeks(12 Weeks)
- Part A and Part B: Progression-Free Survival (PFS) at 12 Weeks(12 Weeks)
- Part A and Part B: Overall Survival (OS) at 24 Weeks(24 Weeks)
- Part A and Part B: Area Under the Concentration-Time Curve (AUC) of DEM301 and Protocol-Specified Analytes(At protocol-specified pharmacokinetics (PK) sampling time points, up to approximately 24 months)
- Part A and Part B: Terminal Elimination Half-Life (t½) of DEM301 and Protocol-Specified Analytes(At protocol-specified PK sampling time points, up to approximately 24 months)
- Part A and Part B: Maximum Concentration (Cmax) of DEM301 and Protocol-Specified Analytes(At protocol-specified PK sampling time points, up to approximately 24 months)
- Part A and Part B: Immunogenicity of DEM301(At protocol-specified PK sampling time points, up to approximately 24 months)
- Progression-Free Survival (PFS) at 12 Weeks(12 Weeks)
- Overall Survival (OS) at 24 Weeks(24 Weeks)
- Disease Control Rate (DCR) at 12 Weeks(12 Weeks)
- Maximum Tolerated Dose (MTD) of DEM301, if Applicable(At completion of Dose Escalation, approximately 12 months)
- Recommended Dose(s) for Expansion (RDEs) of DEM301(At completion of Dose Escalation, approximately 12 months)
- Objective Response Rate (ORR) at 12 Weeks(12 weeks)
- Duration of Response (DoR)(Up to approximately 24 months)
- Area Under the Concentration-Time Curve (AUC) of DEM301 and Protocol-Specified Analytes(At protocol-specified pharmacokinetics (PK) sampling time points, up to approximately 24 months)
- Terminal Elimination Half-Life (t½) of DEM301 and Protocol-Specified Analytes(At protocol-specified PK sampling time points, up to approximately 24 months)
- Maximum Concentration (Cmax) of DEM301 and Protocol-Specified Analytes(At protocol-specified PK sampling time points, up to approximately 24 months)
- Immunogenicity of DEM301(At protocol-specified PK sampling time points, up to approximately 24 months)