First-in-human (FIH), Open-Label, Phase 1a (Dose Escalation)/Phase 1b (Expansion Cohort) Trial of BJ-001 as a Single Agent and in Combination With Pembrolizumab in Patients With Locally Advanced/Metastatic Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 92
- 试验地点
- 5
- 主要终点
- Frequency of adverse events (AEs) and SAE
研究概览
简要总结
The purpose of this study is to assess the safety and tolerability of BJ-001, a human IL-15 fusion protein, administered via subcutaneous injections, as a single agent and in combination with pembrolizumab in adult patients with Locally Advanced/Metastatic Solid 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
盲法说明
no masking is used. All involved know the identity of the intervention assignment.
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
- •Phase 1a patients must have locally advanced or metastatic solid tumors,
- •Phase 1b patients must have locally advanced or metastatic and/or non-resectable head and neck squamous cell carcinoma, cholangiocarcinoma, stomach cancer, melanoma, pancreatic cancer, NSCLC (as high expression of αVβ3, αVβ5, or αVβ6 have been reported for these tumors)
- •Measurable disease: For Phase 1a patients can have non-measurable or measurable disease. For all other parts: measurable disease defined by RECIST v1.1 is required
- •For Phase 1a Part 3 and Phase 1b patients (combination treatment) must be refractory or relapsed to anti-PD-1, anti-PD-L1 or anti-CTLA4 checkpoint inhibitors for all tumor types, For Part 1 and Part 2 of Phase 1a (BJ-001 single agent treatment) both checkpoint inhibitor naïve or refractory/relapsed patients will be considered.
- •Patient who have diagnosis for which treatment with pembrolizumab to be enrolled. Patients previously treated with pembrolizumab and who have progressed are eligible. to be enrolled.
- •Adequate hematologic function,
- •Adequate hepatic function, defined by all of the following:
- •Adequate renal function defined by estimated creatinine clearance ≥ 45 mL/min (Cockcroft and Gault formula
- •ECOG Performance Status (PS) of 0-
- •No history of any hematopoietic malignancy.
- •No active or history of clinically significant autoimmune disease (as defined by previously requiring immunosuppressive therapy).
排除标准
- •Pregnant or nursing females.
- •Receipt of any investigational product or any approved anticancer drug(s) or biological product(s) within 4 weeks prior to the first dose of study drug. Exceptions: Hormone replacement therapy, testosterone, or oral contraceptives (LHRH antagonists are allowed).
- •Patients previously treated with an anti PD-1/PD-L1 targeting agent who have had any prior history of immune-mediated pneumonitis, any immune-mediated toxicity of ≥ Grade 3,
- •Patients with a history of severe allergic or anaphylactic reactions to human mAb therapy or known hypersensitivity.
- •Patients with a history of pneumonitis, myocarditis, history of Stevens-Johnson syndrome or toxic epidermal necrolysis.
- •Patients who have undergone a bone marrow transplantation, solid organ transplantation, or stem cell transplant.
- •Patients with unresolved AEs > Grade 1 from prior anticancer therapy.
- •Patients who have received prior interferon or IL-2 therapy less than 4 weeks prior to enrollment.
- •Uncontrolled primary central nervous system (CNS) tumors or CNS metastases; based on screening.
- •Patients with active autoimmune disease or a documented medical history of autoimmune disease managed by replacement therapy.
研究组 & 干预措施
Arm 1; BJ-001
Phase 1a Part 1, Part 2, and Part 4: dose escalation for BJ-001 as single agent
干预措施: BJ-001 (Drug)
Arm 2; BJ-001 and pembrolizumab
Phase 1a Part 3 and Part 5: dose escalation for BJ-001 in combination with Pembrolizumab
Phase 1b: expansion cohorts for the combination of BJ-001 and pembrolizumab
干预措施: BJ-001 (Drug)
Arm 2; BJ-001 and pembrolizumab
Phase 1a Part 3 and Part 5: dose escalation for BJ-001 in combination with Pembrolizumab
Phase 1b: expansion cohorts for the combination of BJ-001 and pembrolizumab
干预措施: Pembrolizumab (Drug)
结局指标
主要结局
Frequency of adverse events (AEs) and SAE
时间窗: 90 days after the last dose
To assess the safety and tolerability of BJ-001 as a single agent administered s.c. at escalating dose levels in adults with solid tumors.
Severity of AEs in patients with solid tumors enrolled in the study.
时间窗: From Day 1 of treatment up to 30 days after last dose
To assess the safety and tolerability of s.c. BJ-001 administered at escalating dose levels in combination with Pembrolizumab inhibitor. in adults with solid tumors.
Dose limiting toxicities (DLTs) BJ-001 as a single agent
时间窗: at the end of week 4 after first dose
To determine the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) of BJ-001 as a single agent.
Dose limiting toxicities (DLTs) BJ-001 in combination with pembrolizumab inhibitor.
时间窗: at the end of week 4 after first dose
To determine the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) of s.c. BJ-001 administered at escalating dose levels in combination with pembrolizumab in adults with solid tumors.
次要结局
- Immunogenicity of BJ-001 as a single agent and in combination with Pembrolizumab.(90 days after last dose)
- Pharmacokinetic (PK) AUC0-τ samples patients treated with BJ-001 as a single agent and in combination with Pembrolizumab.(24 weeks)
- Pharmacokinetic (PK) Cmax samples patients treated with BJ-001 as a single agent and in combination with Pembrolizumab.(24 weeks)
- Pharmacokinetic (PK) Ctrough samples patients treated with BJ-001 as a single agent and in combination with Pembrolizumab.(24 weeks)
- Pharmacokinetic (PK) Tmax samples patients treated with BJ-001 as a single agent and in combination with Pembrolizumab.(24 weeks)