Phase 1/2 Study of BDC-1001 as a Single Agent and in Combination With Nivolumab in Patients With Advanced HER2-Expressing Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 175
- 试验地点
- 21
- 主要终点
- Incidence of adverse events (AEs) and serious adverse events (SAEs)
研究概览
简要总结
A first-in-human study using BDC-1001 as a single agent and in combination with nivolumab in HER2 expressing advanced malignancies
详细描述
This study has four parts. Part 1 is a dose escalation of BDC-1001 as a single agent to determine the maximum tolerated dose (MTD), recommended Phase 2 dose (RP2D), or maximum protocol dose (MPD) recommended for Part 3. In Part 3, the selected dose will be administered as monotherapy to patients with selected advanced malignancies. Part 2 is a dose escalation of BDC-1001 in combination with nivolumab to determine the maximum tolerated dose (MTD), recommended Phase 2 dose (RP2D), or maximum protocol dose (MPD) recommended for Part 4. In Part 4, the selected dose will be administered in combination with nivolumab to patients with selected advanced malignancies.
Bolt amended the protocol to transition any subjects still receiving BDC-1001 to continue receiving BDC-1001 in the Maintenance Phase. Subjects remaining on BDC-1001 will continue to receive BDC-1001 until a criterion for discontinuation has been met.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Patient must have an advanced solid tumor with documented HER2-protein expression or gene amplification for which approved therapies have been exhausted or are not clinically indicated.
- •Measurable disease as determined by RECIST v.1.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Tumor tissue (archival or collected prior to the study start) available for exploratory biomarker evaluation.
排除标准
- •History of severe hypersensitivity to any ingredient of the study drug(s), including trastuzumab or other monoclonal antibody.
- •Previous treatment with a TLR 7, TLR 8 or a TLR 7/8 agonist.
- •Impaired cardiac function or history of clinically significant cardiac disease
- •Human Immunodeficiency virus (HIV) infection, active hepatitis B infection, or hepatitis C infection.
- •Active SARS-CoV-2 infection
- •Untreated central nervous system (CNS), epidural tumor or metastasis, or brain metastasis.
- •Other protocol defined inclusion/exclusion criteria may apply.
研究组 & 干预措施
Single agent BDC-1001
Escalating doses followed by expansion targeting HER2-expressing advanced malignancies
干预措施: BDC-1001 (Drug)
Combination BDC-1001 plus nivolumab
Escalating doses followed by expansion targeting HER2-expressing advanced malignancies
干预措施: BDC-1001 (Drug)
Combination BDC-1001 plus nivolumab
Escalating doses followed by expansion targeting HER2-expressing advanced malignancies
干预措施: Nivolumab (Drug)
结局指标
主要结局
Incidence of adverse events (AEs) and serious adverse events (SAEs)
时间窗: 2 years
Escalation period
Incidence of potential-immune related toxicities
时间窗: 2 years
Escalation period
Incidence and nature of dose-limiting toxicities (DLTs)
时间窗: up to 21 days
Escalation period
Maximum tolerable dose (MTD) or a tolerated dose below MTD
时间窗: 2 years
Escalation period
Objective response rate (ORR) of confirmed complete or partial responses (CR, PR)
时间窗: 2 years
Expansion period
次要结局
- PK (t1/2) of BDC-1001(2 years)
- PK (CL) of BDC-1001(2 years)
- Objective response rate (ORR) using RECIST 1.1(2 years)
- Progression Free Survival (PFS)(2 years)
- PK (AUC0-t) of BDC-1001(2 years)
- PK (Vz) of BDC-1001(2 years)
- Disease control rate (DCR) of confirmed CR, PR, or stable disease (SD) lasting 4 or more weeks(2 years)
- Incidence of adverse events (AEs) and serious adverse events (SAEs)(2 years)
- PK (AUC0-inf) of BDC-1001(2 years)
- Duration of response (DOR)(2 years)
- Incidence of potential-immune related toxicities(2 years)
- PK (Cmax) of BDC-1001(2 years)
- PK (Cmin) of BDC-1001(2 years)
- Incidence of anti-BDC-1001 antibodies(2 years)