Phase I/Ib, Open-label, Multiple Ascending Dose, First-in-Human Study, to Investigate the Safety, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of INT-1B3 in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 25
- 试验地点
- 4
- 主要终点
- Recommended Phase 2 Dose of INT-1B3
研究概览
简要总结
This is a 2 part, multi-center, open-label, First-in-Human clinical study to evaluate the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of INT-1B3 in the treatment of patients with advanced solid tumors.
详细描述
The investigational medicinal product INT-1B3 is a lipid nanoparticle formulated microRNA (miR-193a-3p) mimic destined for therapeutic intervention in oncology. Preclinical work showed that INT-1B3 has a multi-target mechanism of action with an anti-proliferative, anti-metastatic, anti-migration, cell cycle disruption, induction of apoptosis effect and modulation on the tumor microenvironment leading to significant induction of T cell-mediated immune response.
The first part of the study (Phase I) is a dose-escalation phase to determine the maximal tolerated dose and the recommended Phase 2 dose, as well as the safety profile of INT-1B3 in patients with advanced malignancies.The subsequent expansion phase of the study (Phase Ib) will further explore safety, pharmacokinetics, pharmacodynamic responses, and antitumor activity of INT-1B3 in patients with selected cancer types treated at the recommended phase 2 dose.
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
- •Patient provided a signed written informed consent before any screening procedure
- •Patient is male or female, ≥18 years of age (adult patients)
- •Patient with histologically or cytologically confirmed advanced and/or metastatic solid tumor, with progressive disease at baseline, for whom no standard treatment is available or who have declined standard therapy
- •Patient with evaluable disease per RECIST v1.1, iRECIST
- •Patient with a predicted life expectancy of > 12 weeks
- •Patient with Eastern Cooperative Oncology Group performance status of grade 0 - 1
- •Patient with hemoglobin ≥ 9.0 g/dL, platelet count ≥ 75×109/L, and absolute neutrophil count ≥ 1.0×109/L
- •Patient with adequate renal function
- •Patient with adequate liver function
- •Patient with adequate coagulation tests
- •Female patient of childbearing potential and males should use effective contraception
- •Patient is able and willing to comply with the protocol and the restrictions and assessments therein
排除标准
- •Patients on any other anti-cancer therapy, unless at least 4 weeks (or 5 half-lives, whichever is shorter), have elapsed since the last dose before the first administration of INT-1B
- •At least 2 weeks should have elapsed since receiving non-palliative radiotherapy.
- •Patient with known central nervous system (CNS) metastases, unless previously treated and well-controlled for at least 1 month (defined as clinically stable, no edema, no steroids and stable in 2 scans at least 4 weeks apart)
- •Patient with concomitant second malignancies unless curatively treated at least 2 years before study entry with no additional therapy required or anticipated to be required during the study period
- •Patient with major surgery within 5 weeks before initiating treatment or with minor surgical procedure within 7 days before initiating treatment
- •Patient with active autoimmune disease or persistent immune-mediated toxicity caused by immune checkpoint inhibitor therapy of Grade ≥ 2, except for residual endocrinopathy adequately substituted, vitiligo, Type 1 diabetes mellitus or psoriasis not requiring systemic therapy (>10mg prednisone equivalent)
- •Patient with toxicity (except for alopecia) related to prior anti-cancer therapy and/or surgery, unless the toxicity is either resolved, returned to baseline or grade 1
- •Patient with any active neuropathy > Grade 2 (National Cancer Institute Common Terminology Criteria for Adverse Events v5.0)
- •Patient with any condition requiring concurrent use of systemic immunosuppressants or corticosteroids at a daily dose > 10 mg prednisone equivalent or other immunosuppressive medications within 14 days of study medication administration
- •Patient with evidence of active infection that requires systemic antibacterial, antiviral, or antifungal therapy ≤ 7 days before the first dose of study medication
- •Patient with uncontrolled or significant cardiovascular disease
- •Patient with known active or chronic hepatitis B or C (unless treated with no detectable virus)
- •Patient with known history of exposure to human immunodeficiency virus (HIV)
- •Patient with any known or underlying medical, psychiatric condition, and/or social situations that, in the opinion of the investigator, would limit compliance with study requirements
- •Patient with history of allergy to the study medication or any of its excipients
- •Patient that received packed red blood cells or platelet transfusion within 2 weeks of the first dose of study medication
- •Female patient: pregnant or breastfeeding
研究组 & 干预措施
Phase 1/1b
Phase 1: dose escalation phase with a 'hybrid' 3+3 design in all-comers cancer patients. Approximately 30 patients will be included.
Phase 1b: dose expansion phase in selected tumor types at the recommended phase 2 dose. Approximately 50 patients will be included.
干预措施: INT-1B3 (Drug)
结局指标
主要结局
Recommended Phase 2 Dose of INT-1B3
时间窗: Up to 24 months
Based on dose-limiting toxicities, the maximal tolerated dose and all other available safety, pharmacokinetic/pharmacodynamic data as assessed by the cohort review committee
Incidence and severity of treatment-related adverse events and serious adverse events
时间窗: Up to 24 months
Incidence and severity of adverse events, serious adverse events, according to NCI-CTCAE criteria v 5.0, incidence of dose limiting toxicities (DLTs), adverse events leading to discontinuation and deaths
次要结局
- Maximum plasma concentration(Up to 24 months)
- Area under the curve(Up to 24 months)
- Half-life(Up to 24 months)
- Time of maximum plasma concentration(Up to 24 months)
- Objective response rate of INT-1B3(Up to 24 months)