A Phase 1 Study of SGN-CD47M in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- Seagen Inc.
- 入组人数
- 16
- 试验地点
- 5
- 主要终点
- Number of patients with dose-limiting toxicities (DLTs)
研究概览
简要总结
This trial will study SGN-CD47M to find out whether it is an effective treatment for different types of solid tumors and what side effects (unwanted effects) may occur. The study will have two parts. Part A of the study will find out how much SGN-CD47M should be given for treatment and how often. Part B of the study will use the dose found in Part A and look at how safe and effective the treatment is.
详细描述
This is a dose-escalation study designed to evaluate the safety, tolerability, pharmacokinetics (PK), and antitumor activity of SGN-CD47M in adults with advanced solid tumors. The study will be conducted in 2 parts:
Part A - Dose escalation: Up to approximately 25 patients will be treated to evaluate the safety, tolerability, and PK of SGN-CD47M, and to identify the maximum tolerated dose (MTD) and/or optimal dose.
Part B - Dose expansion: Up to approximately 180 patients will be treated in expansion cohorts at the MTD or optimal dose to further characterize the safety, PK, and antitumor activity of SGN-CD47M.
In eligible patients, standard therapies must have failed, been intolerable, or been considered medically inappropriate by the investigator. If the MTD is not reached in Part A, safety, PK, pharmacodynamic, and biomarker analyses, as well as preliminary antitumor activity, will be used to determine the optimal dose. Patients in Part A may continue on treatment until confirmed progressive disease (PD) or unacceptable toxicity, whichever occurs first. The dose(s) to be examined in Part B will be at or below the MTD and/or the optimal dose determined in Part A.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Histologically or cytologically confirmed metastatic or unresectable solid malignancy within one of the following indications:
- •Soft tissue sarcoma
- •Colorectal carcinoma
- •Non-small cell lung carcinoma
- •Head and neck squamous cell carcinoma
- •Breast carcinoma
- •Ovarian carcinoma
- •Exocrine pancreatic adenocarcinoma
- •Gastric carcinoma
- •Relapsed, refractory, or progressive disease with no appropriate standard therapy available at the time of enrollment
- •ECOG performance status of 0 or 1
- •Measureable disease per the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 at baseline
- •Patients of childbearing potential may not be pregnant, must agree not to become pregnant until at 30 days after last dose of study drug, and must use 2 effective means of birth control.
- •Patients who can father children must use 2 effective means of birth control and must agree not to donate sperm until at least 60 days after last dose of study drug.
排除标准
- •History of another malignancy within 3 years prior to first dose of study drug (exceptions for malignancies with negligible risk of metastasis)
- •Previous exposure to CD47 or SIRPα targeted therapy
- •Chemotherapy, systemic radiotherapy, biologics, other anti-neoplastic or investigational agents, and/or other antitumor treatment with immunotherapy that is not completed 4 weeks prior to first dose of SGN-CD47M. Focal radiotherapy that is not completed 2 weeks prior to the first dose of SGN-CD47M
- •Known active central nervous system metastases
- •Positive for hepatitis B, active hepatitis C infections, positive for human immunodeficiency virus (HIV), or known active or latent tuberculosis
- •History of sickle cell anemia, auto-immune hemolytic anemia, or idiopathic thrombocytopenic purpura
- •Carcinomatous meningitis
- •Red blood cell transfusion within 4 weeks prior to enrollment or platelet transfusion within 2 weeks prior to enrollment
- •Any active Grade 3 or higher viral, bacterial, or fungal infection within 2 weeks prior to first dose
- •History of a cerebral vascular event, unstable angina, myocardial infarction, or cardiac symptoms consistent with New York Heart Association Class III-IV within 6 months prior to first dose
- •Condition requiring systemic treatment with corticosteroids or other immunosuppressive medications within 2 week prior to first dose
- •Active autoimmune disease, autoimmune-related toxicity from prior immuno-oncology-based therapy
- •Estimated life expectancy of less than 12 weeks
研究组 & 干预措施
SGN-CD47M
干预措施: SGN-CD47M (Drug)
结局指标
主要结局
Number of patients with dose-limiting toxicities (DLTs)
时间窗: 28 days
Number of patients with adverse events
时间窗: Up to approximately 24 months
Number of patients with laboratory abnormalities
时间窗: Up to approximately 24 months
次要结局
- Duration of objective response (DOR) per RECIST v1.1(Up to approximately 2.5 years)
- Duration of CR per iRECIST(Up to approximately 2.5 years)
- PFS per iRECIST(Up to approximately 2.5 years)
- Objective response rate (ORR) per RECIST v1.1(Up to approximately 2.5 years)
- DOR per iRECIST(Up to approximately 2.5 years)
- Maximum concentration (Cmax)(Up to approximately 24 months)
- ORR per iRECIST(Up to approximately 2.5 years)
- Duration of complete response (CR) per RECIST v1.1(Up to approximately 2.5 years)
- Progression-free survival (PFS) per RECIST v1.1(Up to approximately 2.5 years)
- Incidence of antidrug antibodies (ADA)(Up to approximately 24 months)
- Overall survival (OS)(Up to approximately 4 years)
- Area under the concentration-time curve (AUC)(Up to approximately 24 months)
- Trough concentration (Ctrough)(Up to approximately 24 months)
- Time to Cmax (Tmax)(Up to approximately 24 months)