Phase 1/2, Multicenter, Open-label, First-in-human Study of DB-1202 Monotherapy in Patients With Advanced Solid Malignant Tumors to Evaluate the Tolerability, Safety, Pharmacokinetics and Antitumor Activity
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 150
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose (MTD) of DB-1202
研究概览
简要总结
This is a dose-escalation and dose-expansion Phase 1/2a trial to evaluate the safety and tolerability of DB-1201 in subjects with advanced solid tumors.
详细描述
This is a multicenter, non-randomized, open-label, multiple-dose, FIH study. The study consists of two parts: Part 1 adopts a rule based "3 + 3" design to identify MTD/RP2D; Part 2 is a dose expansion phase to confirm the safety, tolerability and efficacy in selected 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
- •Male or female at least 18 years old.
- •Has histologically or cytologically confirmed metastatic or locally advanced solid tumors for which no effective standard therapy existed or standard of care has failed or is not considered as an option.
- •Is capable of comprehending study procedures and risks outlined in the informed consent and is willing to provide written consent.
- •Has an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-
- •At least one measurable lesion as assessed by the investigator according to response evaluation criteria in solid tumors (RECIST) version 1.1 criteria.
- •Has adequate organ function within 7 days prior to initiation of the first Treatment Cycle
- •Platelet count ≥ 100 000/mm3
- •Hemoglobin (Hb) ≥ 8.5 g/dL
- •Absolute neutrophil count (ANC) ≥ 1500/mm3
- •Creatinine ≤ 1.5 × upper limit of normal (ULN), or
- •Creatinine clearance ≥ 60 mL/min (modification Cockcroft-Gault equation)
排除标准
- •Has a medical history of symptomatic chronic heart failure (CHF) (New York Heart Association [NYHA] classes II-IV) or serious cardiac arrhythmia requiring treatment.
- •Has a medical history of myocardial infarction or unstable angina within 6 months before Day
- •Has a QTc prolongation to > 470 millisecond (ms) based on a 12-lead electrocardiogram (ECG) in triplicate.
- •Active or prior documented autoimmune disease within the past 2 years. NOTE: Subjects with a history of autoimmune thyroid disease are not excluded. Subjects with vitiligo or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded.
- •Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis).
- •History of primary immunodeficiency.
- •History of allogeneic organ transplant.
- •Has an uncontrolled infection requiring IV injection of antibiotics, antivirals, or antifungals.
- •Known human immunodeficiency virus (HIV) infection, or active hepatitis B or C infection.
- •Is a lactating mother (women who are willing to temporarily interrupt breastfeeding will also be excluded), or pregnant as confirmed by pregnancy tests performed within 7 days prior to initiation of the first Treatment Cycle.
- •Male and female subjects who are unwilling to use adequate contraceptive methods (double barrier or intrauterine contraceptive) during the study and for at least 7 months after the last dose of study drug.
研究组 & 干预措施
DB-1202 Dose Level 1
Enrolled Subjects will receive a single-dose of DB-1202 at Dose Level 1 on Day 1 of each cycle Q3W
干预措施: DB-1202 (Drug)
DB-1202 Dose Level 2
Enrolled Subjects will receive a single-dose of DB-1202 at Dose Level 2 on Day 1 of each cycle Q3W
干预措施: DB-1202 (Drug)
DB-1202 Dose Level 3
Enrolled Subjects will receive a single-dose of DB-1202 at Dose Level 3 on Day 1 of each cycle Q3W
干预措施: DB-1202 (Drug)
DB-1202 Dose Level 4
Enrolled Subjects will receive a single-dose of DB-1202 at Dose Level 4 on Day 1 of each cycle Q3W
干预措施: DB-1202 (Drug)
DB-1202 Dose Level 5
Enrolled Subjects will receive a single-dose of DB-1202 at Dose Level 5 on Day 1 of each cycle Q3W
干预措施: DB-1202 (Drug)
DB-1202 Dose Level 6
Enrolled Subjects will receive a single-dose of DB-1202 at Dose Level 6 on Day 1 of each cycle Q3W
干预措施: DB-1202 (Drug)
DB-1202 Dose Expansion 1
Enrolled Subjects with locally advanced or metastatic primary thyroid cancers with pathology of epithelial tumors that originated from thyroid follicular cells will be enrolled regardless of PD-L1 expression will receive initial dose of DB-1202 Q3W under a 21-day Treatment Cycle with RP2D.
干预措施: DB-1202 (Drug)
DB-1202 Dose Expansion 2
Enrolled Subjects in selected solid malignant tumors can be added will receive initial dose of DB-1202 Q3W under a 21-day Treatment Cycle with RP2D.
干预措施: DB-1202 (Drug)
DB-1202 Dose Expansion 3
Enrolled Subjects in selected solid malignant tumors can be added will receive initial dose of DB-1202 Q3W under a 21-day Treatment Cycle with RP2D.
干预措施: DB-1202 (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD) of DB-1202
时间窗: 12 months
MTD on the data collected during Part 1
Phase 2a: Percentage participants with Serious Adverse Events (SAEs) as assessed by CTCAE v5.0.
时间窗: Up to follow-up period, approximately 1 year post-treatment
Percentage of participants with SAEs in Part 2 graded according to NCI CTCAE v5.0
Phase 1: Percentage of Participants with Dose-Limiting Toxicities (DLTs) as assessed by CTCAE v5.0
时间窗: up to 21 days after Cycle 1 Day 1
Percentage of participants in Part 1 with DLTs
Phase 1: Percentage of Participants with Treatment Emergent Adverse Events (TEAEs) as assessed by CTCAE v5.0
时间窗: Up to follow-up period, approximately 1 year post-treatment
Percentage of participants with AEs in Part 1 graded according to NCI CTCAE v5.0
Phase 1: Recommended Phase 2 Dose (RP2D) of DB-1202
时间窗: 12 months
RP2D of DB-1202 based on the data collected during Part 1
Phase 1: Percentage of Participants with Serious Adverse Events (SAEs) as assessed by CTCAE v5.0.
时间窗: Up to follow-up period, approximately 1 year post-treatment
Percentage of Participants with SAEs in Part 1 graded according to NCI CTCAE v5.0
Phase 2a: Percentage of Participants with Treatment Emergent adverse events (TEAEs) as assessed by CTCAE v5.0.
时间窗: Up to follow-up period, approximately 1 year post-treatment
Percentage of participants with AEs in Part 2 graded according to NCI CTCAE v5.0
Percentage of Objective Response Rate (ORR) as assessed by RECIST 1.1.
时间窗: Up to follow-up period, approximately 1 year post-treatment
The percentage of subjects who had a best response rating of CR and PR, for Part 2 only which was maintained ≥4 weeks
次要结局
- Phase 1 & Phase 2a: Pharmacokinetic-Cmax(within 8 cycles (each cycle is 21 days))
- Phase 1 & Phase 2a: Pharmacokinetic-Tmax(within 8 cycles (each cycle is 21 days))
- Phase 1 & Phase 2a: Pharmacokinetic-T1/2(within 8 cycles (each cycle is 21 days))
- Phase 1 & Phase 2a: Pharmacokinetic-AUC(within 8 cycles (each cycle is 21 days))