Phase 1, Two-Part, Multicenter, Non-randomized, Open-label, Multiple Dose First-In-Human Study of DS-8201A, in Subjects With Advanced Solid Malignant Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 292
- 试验地点
- 14
- 主要终点
- Objective Response Rate (ORR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases)
研究概览
简要总结
This is an open-label, two-part, multicenter study to evaluate the safety and tolerability of DS-8201a in participants with advanced solid malignant tumors.
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
- •Eastern Cooperative Oncology Group performance status( PS) of 0 or
- •Left Ventricular Ejection Fraction (LVEF) ≥ 50%
- •Advanced/unresectable or metastatic breast cancer or gastric or gastroesophageal junction adenocarcinoma that is refractory to or intolerable with standard treatment, or for which no standard treatment is available.
- •Advanced breast cancer with HER2 overexpression that is refractory to or intolerable with standard treatment, or for which no standard treatment is available.
- •Treated with ado-trastuzumab emtansine (T-DM1)
- •Advanced gastric or gastroesophageal junction adenocarcinoma with HER2 overexpression that is refractory to or intolerable with standard treatment, or for which no standard treatment is available.
- •Treated with trastuzumab
- •Advanced breast cancer with HER2 low expression that is refractory to or intolerable with standard treatment, or for which no standard treatment is available.
- •Satisfy at least one of the following criteria
- •Advanced/unresectable or metastatic solid malignant tumor with HER2 expression other than breast cancer and gastric or gastroesophageal junction adenocarcinoma that is refractory to or intolerable with standard treatment, or for which no standard treatment is available.
- •Advanced/unresectable or metastatic tumor with HER2 mutation that is refractory to or intolerable with standard treatment, or for which no standard treatment is available.
- •Advanced breast cancer with HER2 overexpression that is refractory to or intolerable with standard treatment, or for which no standard treatment is available.
- •Treated with ado-trastuzumab emtansine (T-DM1) (patients with HER2 overexpression only)
排除标准
- •Has a medical history of symptomatic Congestive Heart Failure (CHF) (NYHA classes II-IV) or serious cardiac arrhythmia.
- •Has a medical history of myocardial infarction or unstable angina.
- •Has a QTc prolongation to > 450 millisecond (ms) in males and > 470 ms in females.
- •Has a medical history of clinically significant lung diseases
研究组 & 干预措施
Part 1 Dose escalation
Part 1 is a dose escalation to identify the Maximum Tolerated dose (MTD) or the recommended phase 2 dose of DS-8201a guided by the modified continuous reassessment method using a Bayesian logistic regression model following escalation with overdose control principal.
干预措施: DS-8201a (DP1) (Drug)
Part 1 Dose escalation
Part 1 is a dose escalation to identify the Maximum Tolerated dose (MTD) or the recommended phase 2 dose of DS-8201a guided by the modified continuous reassessment method using a Bayesian logistic regression model following escalation with overdose control principal.
干预措施: DS-8201a (DP) (Drug)
Part 2 Dose expansion
Part 2 is a dose expansion to examine the safety and efficacy of DS-8201a and it is consist of multiple cohorts: in subjects with trastuzumab emtansine (T-DM1)-treated HER2 overexpressing breast cancer (Part 2a); trastuzumab-treated HER2 overexpressing gastric or gastroesophageal junction adenocarcinoma (Part 2b); HER2 low expressing breast cancer (Part 2c), HER2 expressing other solid malignant tumor (Part 2d); HER2 expressing breast cancer (Japan only; Part 2e)
干预措施: DS-8201a (DP1) (Drug)
Part 2 Dose expansion
Part 2 is a dose expansion to examine the safety and efficacy of DS-8201a and it is consist of multiple cohorts: in subjects with trastuzumab emtansine (T-DM1)-treated HER2 overexpressing breast cancer (Part 2a); trastuzumab-treated HER2 overexpressing gastric or gastroesophageal junction adenocarcinoma (Part 2b); HER2 low expressing breast cancer (Part 2c), HER2 expressing other solid malignant tumor (Part 2d); HER2 expressing breast cancer (Japan only; Part 2e)
干预措施: DS-8201a (DP2) (Drug)
Part 2 Dose expansion
Part 2 is a dose expansion to examine the safety and efficacy of DS-8201a and it is consist of multiple cohorts: in subjects with trastuzumab emtansine (T-DM1)-treated HER2 overexpressing breast cancer (Part 2a); trastuzumab-treated HER2 overexpressing gastric or gastroesophageal junction adenocarcinoma (Part 2b); HER2 low expressing breast cancer (Part 2c), HER2 expressing other solid malignant tumor (Part 2d); HER2 expressing breast cancer (Japan only; Part 2e)
干预措施: DS-8201a (DP) (Drug)
结局指标
主要结局
Objective Response Rate (ORR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases)
时间窗: From 6 months postdose of last participant up to 3 years 5 months
Objective response rate (ORR) by independent central review was defined as the proportion of participants who achieve either complete response \[CR\] or partial response \[PR\] per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR was defined as a disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions. HER2-positive other solid tumors included participants with salivary/submandibular/parotid gland (8 participants), breast with HER2-mutation (2 participants), endometrial (2 participants), esophageal (2 participants), Paget's disease (2 participants), cholangiocarcinoma (1 participant), extraskeletal myxoide chondrosarcoma (1 participant), gallbladder (1 participant), pancreatic (1 participant), small intestine (1 participant), uterine cervix (1 participant) and HER2-low gastric/GEJ (1 participant who received 5.4 mg/kg) cancer.
次要结局
- Overall Survival Among Participants With Advanced Solid Malignant Tumors (Dose Expansion Phases)(From 6 months postdose of last participant up to 3 years 5 months)
- Pharmacokinetic Analysis: Time of Maximum Plasma Concentration (Tmax) of Serum DS-8201a Following First Dose(Post first dose up to Day 147)
- Duration of Response (DoR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Expansion Phases)(From 6 months postdose of last participant up to 3 years 5 months)
- Pharmacokinetic Analysis: Terminal Elimination Half-life (t1/2) of Serum DS-8201a Following First Dose(Post first dose up to Day 147)
- Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases)(From 6 months postdose of last participant up to 3 years 5 months)
- Progression-free Survival Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Expansion Phases)(From 6 months postdose of last participant up to 3 years 5 months)
- Disease Control Rate (DCR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases)(From 6 months postdose of last participant up to 3 years 5 months)
- Time to Response (TTR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Expansion Phases)(From 6 months postdose of last participant up to 3 years 5 months)
- Pharmacokinetic (PK) Analysis: Area Under the Concentration Versus Time Curve (AUC) of Serum DS-8201a Following First Dose(Post first dose up to Day 147)
- Pharmacokinetic Analysis: Maximum (Peak) Observed Serum Concentration (Cmax) of Serum DS-8201a Following First Dose(Post first dose up to Day 147)
- Overview of Treatment-emergent Adverse Events(Baseline up to 28 days after the last dose of study drug, up to 3 years 5 months)