A Phase 1/2, Multicenter, Open-Label, First-in-Human Study to Assess the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of DB-1324 in Participants With Advanced/Metastatic Gastrointestinal Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 127
- 试验地点
- 15
- 主要终点
- Dose Escalation and Backfill parts: Percentage of Participants with Dose-Limiting Toxicities (DLTs) as assessed by CTCAE v5.0.
研究概览
简要总结
This study, the first clinical trial, aims to determine the safety, tolerability, pharmacokinetics, pharmacodynamics, maximum tolerated dose, and antitumor activity of DB-1324.
详细描述
This is a multicenter, open-label, multiple-dose, FIH Phase 1/2 study to explore the safety, tolerability, and efficacy of DB-1324 in participants with malignant GI tumors.
The Phase 1, which includes Dose Escalation, Backfill, and Dose Expansion to identify the MTD and determine the RDEs and RP2D.
Phase 2 will confirm the safety, tolerability, and explore efficacy in selected malignant GI tumors.
For both Phase 1 and Phase 2, participants will receive study treatment until 1) disease progression, 2) loss of clinical benefit in the opinion of the investigator, 3) unacceptable toxicity, 4) withdrawal from study treatment by participant, 5) lost to follow up, or 6) another criterion for discontinuation is met, whichever occurs first.
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
- •Pathologically documented advanced/unresectable, or metastatic GI tumor.
- •Have relapsed or progressed on or after standard systemic treatments, or are intolerant to standard treatment, or for which no standard treatment is available.
- •At least one measurable lesion as assessed by the investigator according to response evaluation criteria in RECIST v1.
- •Has a life expectancy of ≥ 3 months.
- •Has an ECOG PS of 0-
- •Has LVEF ≥ 50% by either ECHO or MUGA within 28 days before enrollment.
- •Has adequate organ functions within 7 days prior to Day 1 of Cycle
- •Has an adequate treatment washout period before Day 1 of Cycle
- •Participants are willing to provide archived tumor tissue or undergo a tumor biopsy for the measurement of CDH17 levels and other biomarkers.
- •Other protocol-defined Inclusion criteria apply.
排除标准
- •Prior treatment with CDH17 targeted therapy.
- •Prior treatment with ADC with topoisomerase I inhibitor.
- •Has chronic enteritis or inflammatory bowel disease. Or has clinically significant bleeding of GI tract or adjacent organs within 1 month prior to the first dose of study treatment. Or has clinically significant obstruction and/or perforation and/or fistulae (including prior GI fistula operation) of GI tract or adjacent tissues within 6 months prior to the first dose of study treatment.
- •Uncontrolled or significant cardiovascular disease.
- •Has a medical history of cerebrovascular accident including transient ischemic attack within 6 months before enrollment.
- •Has a history of (non-infectious) ILD/pneumonitis that required steroids, or has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
- •Have a lung-specific intercurrent clinically significant illness.
- •Has an uncontrolled infection requiring intravenous injection of antibiotics, antivirals, or antifungals.
- •Has clinically active brain metastases.
- •Has unresolved toxicities from previous anticancer therapy.
- •Other protocol-defined Exclusion criteria apply.
研究组 & 干预措施
DB-1324 Phase 1 Dose escalation
Enrolled Subjects will receive a single-dose of DB-1324 at different Dose Level or different dose regimen
干预措施: DB-1324 (Drug)
DB-1324 Phase 1 Backfill
Participants with GI cancers who have received no more than 3 prior lines of systemic therapy may be backfilled at the selected dose regimens to further explore the safety, efficacy, PK, and pharmacodynamics of DB-1324.
干预措施: DB-1324 (Drug)
DB-1324 Phase 1 Dose Expansion
Two or more appropriate dose regimens of DB-1324, determined from the emerging dose escalation (and backfill) data, will be explored for preliminary efficacy and safety of DB-1324.
干预措施: DB-1324 (Drug)
DB-1324 Phase 2
Phase 2 will consist of one or more cohorts intended to confirm early signals of efficacy identified in Phase 1.
干预措施: DB-1324 (Drug)
结局指标
主要结局
Dose Escalation and Backfill parts: Percentage of Participants with Dose-Limiting Toxicities (DLTs) as assessed by CTCAE v5.0.
时间窗: Up to safety follow-up visit, approximately 30 days post-treatment
Percentage of participants in dose escalation and backfill parts with DLTs
Dose Escalation and Backfill parts: Percentage of Participants with Serious Adverse Events (SAEs) as assessed by CTCAE v5.0.
时间窗: Up to safety follow-up visit, approximately 30 days post-treatment
Percentage of participants with SAEs in dose escalation and backfill parts graded according to NCI CTCAE v5.0
Dose Escalation and Backfill parts: Percentage of participants with Treatment Emergent Adverse Events (TEAEs) , Grade ≥ 3 TEAE, TEAE leading to dose reduction/interruption/discontinuation
时间窗: Up to safety follow-up visit, approximately 30 days post-treatment
Percentage of participants who experienced any of the above TEAEs in dose escalation and backfill parts graded according to NCI CTCAE v5.0
Dose Escalation and Backfill parts: Maximum Tolerated Dose(MTD) of DB-1324
时间窗: Up to safety follow-up visit, approximately 30 days post-treatment
MTD will be determined by evaluating the incidence of DLTs during the DLT assessment period.
次要结局
- Dose Escalation, Backfill and Expansion parts: Recommended Phase 2 Dose(RP2D)(From the beginning of first patient in (FPI) to the end of study, approximately 36 months)
- Dose Escalation and Backfill parts: Recommended Dose for Expansions(RDEs)(Up to the completion of Phase 1, assessed up to 12 months)
- Dose Escalation and Backfill parts: Objective Response Rate (ORR)(From the beginning of first patient in (FPI) to the end of study, approximately 36 months)
- Dose Escalation and Backfill parts: Duration of Response (DoR)(From the beginning of first patient in (FPI) to the end of study, approximately 36 months)
- Dose Escalation and Backfill parts: Disease Control Rate (DCR)(From the beginning of first patient in (FPI) to the end of study, approximately 36 months)
- Dose Escalation and Backfill parts: Pharmacokinetic-AUC0-τ(Up to safety follow up visit, approx. 30 days post-treatment)
- Dose Escalation and Backfill parts: Time to Response (TTR)(From the beginning of first patient in (FPI) to the end of study, approximately 36 months)
- Dose Escalation and Backfill parts: Pharmacokinetic-Tmax(Up to safety follow up visit, approx. 30 days post-treatment)
- Dose Escalation and Backfill parts: Pharmacokinetic-Cthroug(Up to safety follow up visit, approx. 30 days post-treatment)
- Dose Escalation and Backfill parts: Progression Free Survival (PFS)(From the beginning of first patient in (FPI) to the end of study, approximately 36 months)
- Dose Escalation and Backfill parts: Pharmacokinetic-AUClast(Up to safety follow up visit, approx. 30 days post-treatment)
- Dose Escalation and Backfill parts: Pharmacokinetic-Cmax(Up to safety follow up visit, approx. 30 days post-treatment)
- Dose Escalation and Backfill parts: Anti-drug antibody (ADA) prevalence(Up to safety follow up visit, approx. 30 days post-treatment)