A Phase 1/2a, Multicenter, Open-Label, First in Human Study to Assess the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of DB-1305 in Subjects With Advanced/Metastatic Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 1,123
- 试验地点
- 107
- 主要终点
- Phase 1: Percentage of Participants with Dose-Limiting Toxicities (DLTs) as assessed by National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0.
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-1305/BNT325 in subjects with advanced solid tumors.
详细描述
This is a multicenter, open-label, multiple-dose, first in human (FIH) study. The study consists of two parts: Part 1 adopts an accelerated titration at first dose level followed with classic "3+3" design to identify the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D); Part 2 is a dose expansion phase to confirm the safety, tolerability and explore efficacy in selected malignant solid tumors at the MTD/the RP2D. This study will enroll subjects with advanced/unresectable, recurrent, or metastatic malignant solid tumors.
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
- •Male or female adults (defined as ≥ 18 years of age or acceptable age according to local regulations at the time of voluntarily signing of informed consent).
- •Histologically or cytologically confirmed unresectable advanced/ metastatic solid tumors who have relapsed or progressed on or after standard systemic treatments or for which no standard treatment is available.
- •At least one measurable lesion as assessed by the investigator according to RECIST version 1.1 criteria.
- •Has a life expectancy of ≥ 3 months.
- •Has an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-
- •Has Left Ventricular Ejection Fraction (LVEF) ≥ 50% by either echocardiography (ECHO) or multiple-gated acquisition (MUGA) within 28 days before enrollment.
- •Has adequate organ functions within 7 days prior to Day 1 of Cycle
- •Has adequate treatment washout period prior to Day 1 of Cycle
- •Is willing to provide pre-existing resected tumor samples or undergo fresh tumor biopsy for the measurement of Trop-2 level and other biomarkers if not contraindicated.
- •Is capable of comprehending study procedures and risks outlined in the informed consent and able to provide written consent and agree to comply with the requirements of the study and the schedule of assessments.
排除标准
- •Has a medical history of symptomatic congestive 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 enrollment.
- •Has an average of Fredericia's formula-QT corrected interval (QTcF) prolongation to > 470 millisecond (ms) in males and females based on a 12-lead electrocardiogram (ECG) in triplicate.
- •Has a medical history of non-infectious Interstitial Lung Diseases (ILD)/pneumonitis or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
- •Has a lung-specific intercurrent clinically significant illness.
- •Has an uncontrolled infection requiring IV injection of antibiotics, antivirals, or antifungals.
- •Subjects have human immunodeficiency virus (HIV) infection with acquired immune deficiency syndrome (AIDS) defining illness are not eligible for enrollment; However, subjects have had HIV infection with a cluster of differentiation 4 (CD4)+ T cell count > 350 cells/µL and no history of an AIDS-defining illness are eligible for entry.
- •NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
DB-1305/BNT325 Dose Level 4
Enrolled subjects will receive DB-1305/BNT325 at Dose Level 4
干预措施: DB-1305/BNT325 (Drug)
DB-1305/BNT325 Dose Level 2
Enrolled subjects will receive DB-1305/BNT325 at Dose Level 2
干预措施: DB-1305/BNT325 (Drug)
DB-1305/BNT325 Dose Level 1
Enrolled subjects will receive DB-1305/BNT325 at Dose Level 1
干预措施: DB-1305/BNT325 (Drug)
DB-1305/BNT325 Dose Level 5
Enrolled subjects will receive DB-1305/BNT325 at Dose Level 5
干预措施: DB-1305/BNT325 (Drug)
DB-1305/BNT325 Dose Level 6
Enrolled subjects will receive DB-1305/BNT325 at Dose Level 6
干预措施: DB-1305/BNT325 (Drug)
DB-1305/BNT325 in combination with pembrolizumab
Enrolled subjects will receive DB-1305/BNT325 in combination with pembrolizumab
干预措施: DB-1305/BNT325 (Drug)
DB-1305/BNT325 Dose Expansion 1
subjects with Non-Small Cell Lung Cancer (NSCLC) with actionable genetic alterations (AGAs) who will receive DB-1305/BNT325 on either dose level 1 or dose level 2
干预措施: DB-1305/BNT325 (Drug)
DB-1305/BNT325 Dose Expansion 3
Enrolled subjects with OC who will receive DB-1305/BNT325 on either dose level 1 or dose level 2
干预措施: DB-1305/BNT325 (Drug)
DB-1305/BNT325 Dose Expansion 6
Enrolled subjects with TNBC with treatment failure on sacituzumab govitecan who will receive DB-1305/BNT325 on a selected dose level (RP2D)
干预措施: DB-1305/BNT325 (Drug)
DB-1305/BNT325 Dose Expansion 9
Enrolled subjects with Cervical Cancer (CC) who will receive DB-1305/BNT325 on a selected dose level (RP2D)
干预措施: DB-1305/BNT325 (Drug)
Experimental: DB-1305/BNT325 Dose Expansion 10
Enrolled subjects with pancreatic cancer who will receive DB-1305/BNT325 on a selected dose level (RP2D)
干预措施: DB-1305/BNT325 (Drug)
DB-1305/BNT325 in combination with pembrolizumab
Enrolled subjects will receive DB-1305/BNT325 in combination with pembrolizumab
干预措施: Pembrolizumab (Combination Product)
Experimental: DB-1305/BNT325 Dose Level 8
Enrolled subjects will receive DB-1305/BNT325 at Dose Level 8
干预措施: DB-1305/BNT325 (Drug)
Experimental: DB-1305/BNT325 Dose Expansion PM1
Enrolled subjects with NSCLC without AGAs who will receive DB-1305/BNT325 on a selected dose level in combination with BNT327
干预措施: BNT327 (Drug)
DB-1305/BNT325 Dose Expansion PB1
Enrolled subjects with NSCLC without AGAs who will receive DB-1305/BNT325 on a selected dose level in combination with pembrolizumab
干预措施: Pembrolizumab (Combination Product)
Experimental: DB-1305/BNT325 in combination with BNT327
Enrolled subjects will receive DB-1305/BNT325 in combination with BNT327
干预措施: DB-1305/BNT325 (Drug)
Experimental: DB-1305/BNT325 Dose Expansion PM5
Enrolled subjects with TNBC who will receive DB-1305/BNT325 on a selected dose level in combination with BNT327
干预措施: DB-1305/BNT325 (Drug)
Experimental: DB-1305/BNT325 Dose Expansion PM4
Enrolled subjects with OC who will receive DB-1305/BNT325 on a selected dose level in combination with BNT327
干预措施: BNT327 (Drug)
DB-1305/BNT325 Dose Expansion PM6
Enrolled subjects with NSCLC without AGA who will receive DB-1305/BNT325 on a selected dose level in combination with BNT327
干预措施: BNT327 (Drug)
Experimental: DB-1305/BNT325 Dose Expansion PM1
Enrolled subjects with NSCLC without AGAs who will receive DB-1305/BNT325 on a selected dose level in combination with BNT327
干预措施: DB-1305/BNT325 (Drug)
Experimental: DB-1305/BNT325 Dose Expansion PM2
Enrolled subjects with NSCLC with AGAs who will receive DB-1305/BNT325 on a selected dose level in combination with BNT327
干预措施: DB-1305/BNT325 (Drug)
Experimental: DB-1305/BNT325 Dose Expansion PM2
Enrolled subjects with NSCLC with AGAs who will receive DB-1305/BNT325 on a selected dose level in combination with BNT327
干预措施: BNT327 (Drug)
Experimental: DB-1305/BNT325 Dose Expansion PM5
Enrolled subjects with TNBC who will receive DB-1305/BNT325 on a selected dose level in combination with BNT327
干预措施: BNT327 (Drug)
Experimental: DB-1305/BNT325 Dose Expansion PM3
Enrolled subjects with CC who will receive DB-1305/BNT325 on a selected dose level in combination with BNT327
干预措施: DB-1305/BNT325 (Drug)
DB-1305/BNT325 Dose Level 3
Enrolled subjects will receive DB-1305/BNT325 at Dose Level 3
干预措施: DB-1305/BNT325 (Drug)
DB-1305/BNT325 Dose Level 7
Enrolled subjects will receive DB-1305/BNT325 at Dose Level 7
干预措施: DB-1305/BNT325 (Drug)
DB-1305/BNT325 Dose Expansion 2
Enrolled subjects with NSCLC without AGAs who will receive DB-1305/BNT325 on either dose level 1 or dose level 2
干预措施: DB-1305/BNT325 (Drug)
DB-1305/BNT325 Dose Expansion 4
Enrolled subjects with BC who will receive DB-1305/BNT325 on a selected dose level (RP2D)
干预措施: DB-1305/BNT325 (Drug)
DB-1305/BNT325 Dose Expansion 5
Enrolled subjects with Triple-Negative Breast Cancer (TNBC) who have progressed on or after standard systemic treatments and without prior treatment of sacituzumab govitecan who will receive DB-1305/BNT325 on a selected dose level (RP2D)
干预措施: DB-1305/BNT325 (Drug)
DB-1305/BNT325 Dose Expansion 7
Enrolled subjects with EC who will receive DB-1305/BNT325 on a selected dose level (RP2D)
干预措施: DB-1305/BNT325 (Drug)
DB-1305/BNT325 Dose Expansion 8
Enrolled subjects with malignant mesothelioma will receive DB-1305/BNT325 on a selected dose level (RP2D)
干预措施: DB-1305/BNT325 (Drug)
DB-1305/BNT325 Dose Expansion 11
Enrolled subjects with Castration-Resistant Prostate Cancer (CRPC) who will receive DB-1305/BNT325 on a selected dose level (RP2D)
干预措施: DB-1305/BNT325 (Drug)
DB-1305/BNT325 Dose Expansion PB1
Enrolled subjects with NSCLC without AGAs who will receive DB-1305/BNT325 on a selected dose level in combination with pembrolizumab
干预措施: DB-1305/BNT325 (Drug)
Experimental: DB-1305/BNT325 in combination with BNT327
Enrolled subjects will receive DB-1305/BNT325 in combination with BNT327
干预措施: BNT327 (Drug)
Experimental: DB-1305/BNT325 Dose Expansion PM3
Enrolled subjects with CC who will receive DB-1305/BNT325 on a selected dose level in combination with BNT327
干预措施: BNT327 (Drug)
Experimental: DB-1305/BNT325 Dose Expansion PM4
Enrolled subjects with OC who will receive DB-1305/BNT325 on a selected dose level in combination with BNT327
干预措施: DB-1305/BNT325 (Drug)
DB-1305/BNT325 Dose Expansion 12
Enrolled subjects with head and neck cancer who will receive DB-1305/BNT325 on a selected dose level (RP2D)
干预措施: DB-1305/BNT325 (Drug)
DB-1305/BNT325 Dose Level 9
Enrolled subjects will receive DB-1305/BNT325 at Dose Level 9
干预措施: DB-1305/BNT325 (Drug)
DB-1305/BNT325 Dose Expansion PM6
Enrolled subjects with NSCLC without AGA who will receive DB-1305/BNT325 on a selected dose level in combination with BNT327
干预措施: DB-1305/BNT325 (Drug)
结局指标
主要结局
Phase 1: Percentage of Participants with Dose-Limiting Toxicities (DLTs) as assessed by National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-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 30 days after last study treatment administration or before starting new anticancer treatment, whichever comes first.
Percentage of participants with TEAEs in Part 1 graded according to NCI CTCAE v5.0
Phase 1: Percentage of Participants with Serious Adverse Events (SAEs) as assessed by CTCAE v5.0.
时间窗: Up 30 days after last study treatment administration or before starting new anticancer treatment, whichever comes first.
Percentage of Participants with SAEs in Part 1 graded according to NCI CTCAE v5.0
Maximum Tolerated Dose (MTD) of DB-1305/BNT325
时间窗: At the end of Cycle 1 (each cycle is 21 days)
MTD on the data collected during Part 1
Phase 1: RP2D of DB-1305/BNT325
时间窗: From first study treatment administration until the initiation of Phase 2a, approximately up to 12 months.
RP2D of DB-1305/BNT325 based on the data collected during Part 1
Phase 2a: Percentage of Participants with TEAEs as assessed by CTCAE v5.0.
时间窗: Up to 30 days after last study treatment administration or before starting new anticancer treatment, whichever comes first.
Percentage of participants with TEAEs in Part 2 graded according to NCI CTCAE v5.0 (secondary outcome measure in cohort 3)
Phase 2a: Percentage participants with SAEs as assessed by CTCAE v5.0.
时间窗: Up to 30 days after last study treatment administration or before starting new anticancer treatment, whichever comes first.
Percentage of participants with SAEs in Part 2 graded according to NCI CTCAE v5.0 (secondary outcome measure in cohort 3)
Phase 2a: Objective Response Rate (ORR) as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
时间窗: Up to disease progression or death or before starting new anticancer treatment or withdrawal from the trial, whichever comes first, approximately up to 12 months.
The percentage of subjects who had a best response rating of CR and PR
次要结局
- Phase 1 & Phase 2a: disease-control rate (DCR)(with 8 cycles (each cycle is 21 days))
- Phase 1 & Phase 2a: time to response (TTR)(with 8 cycles (each cycle is 21 days))
- Phase 1 & Phase 2a: Pharmacokinetic parameters: the area under the concentration-time curve from time 0 to tau [AUC0-tau] of DB-1305/BNT325(within 8 cycles (each cycle is 21 days))
- Phase 1 & Phase 2a: anti-drug antibody (ADA) prevalence: the proportion of subjects who are ADA positive at any point in time (at baseline and post-baseline). ADA incidence: the proportion of subjects having treatment-emergent ADA.(within 8 cycles (each cycle is 21 days))
- Phase 1: ORR will be determined from tumor assessments by investigator per RECIST 1.1(with 8 cycles (each cycle is 21 days))
- Phase 1 & Phase 2a: duration of response (DoR) will be determined from tumor assessments by investigator per RECIST 1.1(with 8 cycles (each cycle is 21 days))
- Phase 1 & Phase 2a: Pharmacokinetic parameters: (the area under the concentration-time curve from the time zero to the last quantifiable concentration [AUC0-last] of DB-1305/BNT325(within 8 cycles (each cycle is 21 days))
- Phase 1 & Phase 2a: Pharmacokinetic parameters: time to Cmax [Tmax] of DB-1305/BNT325(within 8 cycles (each cycle is 21 days))
- Phase 1 & Phase 2a: Pharmacokinetic parameters: trough concentration [Ctrough] of DB-1305/BNT325(within 8 cycles (each cycle is 21 days))
- Phase 1 & Phase 2a: peak observed concentration [Cmax] of DB-1305/BNT325(within 8 cycles (each cycle is 21 days))
- Phase 1 & Phase 2a: progression free survival (PFS) will be determined from tumor assessments by investigator per RECIST 1.1(with 8 cycles (each cycle is 21 days))
- Phase 1 & Phase 2a: overall survival (OS)(with 8 cycles (each cycle is 21 days))