A Phase 1 Dose-Escalation/Expansion Study of SLV-154 in Subjects With Advanced Cancers
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 250
- 试验地点
- 13
- 主要终点
- MTD and/or RDR
研究概览
简要总结
This is a Phase 1 study comprising a Phase 1a dose-escalation portion and a Phase 1b expansion portion evaluating the safety, pharmacokinetics, pharmacodynamics, immunogenicity, and efficacy of SLV-154 across a range of dose levels when administered to subjects with advanced solid tumors.
详细描述
A Bayesian optimal interval (BOIN) design with a target dose-limiting toxicity (DLT) rate for the maximum tolerated dose (MTD) of 27% and an estimated maximum sample size of ~70 subjects will be used to guide the dose escalation and determine the recommended dosing regimen (RDR) of SLV-154. Once the initial RDR is established in the Phase 1a portion of this study, further development in the Phase 1b expansion portion of this study will be considered in patients with specific cancers. In the Phase 1b part of this study, enrollment of each tumor-specific cohort will be performed using a Simon 2-stage optimal design.
SLV-154 will be administered intravenously (IV) in repeated 3-week cycles. Treatment will continue until progressive disease or discontinuation.
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
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Men or women (as appropriate for cancer type) of age ≥12 years.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Histologically or cytologically confirmed diagnosis of advanced cancer as documented in medical records.
- •Presence of metastatic or recurrent locally advanced cancer.
- •Presence of radiographically measurable disease.
- •Prior receipt of one or more commercially available therapies that are indicated within product labelling or recommended under current guidelines as appropriate treatment for the subject's cancer (unless evolving data support application of SLV-154 in previously untreated subjects with high unmet medical need and inadequate and/or poorly tolerated treatment options).
- •Availability of tumor tissue from a fresh tumor biopsy obtained by a core needle, excisional, or incisional biopsy; or punch biopsy (for cutaneous disease); or archival tumor sample from a previous biopsy.
- •Availability of computed tomography (CT) or magnetic resonance imaging (MRI) of chest, abdomen, and pelvis, and/or fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT (if appropriate for tumor type) (with PET from base of the skull to mid-thigh, if performed) within 35 days before study drug administration.
- •Completion of all previous therapy (including surgery, radiotherapy, chemotherapy, targeted therapy, immunotherapy, or investigational therapy) for the treatment of cancer ≥1 week before the start of study drug administration.
- •Adequate hematological profile.
- •Adequate coagulation profile.
- •Adequate hepatic profile.
- •Adequate renal function.
- •Negative viral serology or adequate therapy for human immunodeficiency virus (HIV), hepatitis B (HBV), and hepatitis C (HCV) infection.
- •For female subjects of childbearing potential, a negative serum pregnancy test.
- •For female subjects of childbearing potential, willingness to use a protocol-recommended method of contraception from the start of the screening period until ≥6 months after the final dose of study therapy.
- •For male subjects who can father a child and are having intercourse with females of childbearing potential who are not using adequate contraception, willingness to use a protocol-recommended method of contraception from the start of study therapy until ≥6 months after the final dose of study therapy and to refrain from sperm donation from the start of study therapy until ≥12 months after administration of the final dose of study therapy.
- •Willingness and ability of the subject to comply with scheduled visits, the drug administration plan, protocol-specified laboratory tests, other study procedures (including required tumor biopsy/aspirations and/or radiographic studies), and study restrictions.
- •Evidence of a personally signed informed consent indicating that the subject is aware of the neoplastic nature of the disease and has been informed of the procedures to be followed, the experimental nature of the therapy, alternatives, potential risks and discomforts, potential benefits, and other pertinent aspects of study participation.
排除标准
- •Unstable malignancy involving the central nervous system.
- •Presence of another cancer with disease manifestations or therapy that could adversely affect subject safety or longevity, create the potential for drug-drug interactions, or compromise the interpretation of study results.
- •Uncontrolled ongoing systemic bacterial, fungal, or viral infection (including upper respiratory tract infection) at the time of start of study therapy.
- •Significant cardiovascular event or comorbidity.
- •Significant screening ECG abnormalities.
- •Pregnancy or breastfeeding.
- •Major surgery within 3 weeks before the start of study therapy.
- •Use of a strong inhibitor or inducer of CYP3A4 or CYP1A
- •Concurrent participation in another therapeutic or imaging clinical trial.
- •Other conditions likely to interfere with a subject's ability to participate in the study.
研究组 & 干预措施
Dose Level 5
5.0 mg/kg
干预措施: SLV-154 (Drug)
Dose Level 6
6.5 mg/kg
干预措施: SLV-154 (Drug)
Dose Level 1
0.75 mg/kg
干预措施: SLV-154 (Drug)
Dose Level 2
1.5 mg/kg
干预措施: SLV-154 (Drug)
Dose Level 4
4.0 mg/kg
干预措施: SLV-154 (Drug)
Dose Level 3
3.0 mg/kg
干预措施: SLV-154 (Drug)
结局指标
主要结局
MTD and/or RDR
时间窗: Through the duration of treatment, up to approximately 18 months
Determination of the MTD (maximum tolerated dose) and/or RDR (recommended dosing regimen) for SLV-154
Phase 1a: MTD and/or RDR
时间窗: Through the duration of treatment, up to approximately 18 months
Determination of the MTD (maximum tolerated dose) and/or RDR (recommended dosing regimen) for SLV-154.
Phase 1b: Objective response rate (ORR)
时间窗: Through the duration of treatment, up to approximately 18 months
ORR assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 criteria and defined as the percentage of participants with confirmed complete response (CR) or confirmed partial response (PR).
次要结局
- Time to treatment failure (TTF)(Up to approximately 36 months)
- Overall survival (OS)(Up to approximately 36 months)
- SLV-154 Safety(Through the duration of treatment, up to approximately 18 months)
- Evaluation of use of concomitant medications(Through the duration of treatment, up to approximately 18 months)
- SLV-154 Pharmacokinetics(Varying timepoints through the duration of treatment, up to approximately 18 months)
- Immunogenicity(Varying timepoints through the duration of treatment, up to approximately 18 months)
- Objective Response Rate (ORR)(Through the duration of treatment, up to approximately 18 months)
- Time to Response (TTR)(Up to approximately 36 months)
- SLV-154 administration(Through the duration of treatment, up to approximately 18 months)
- Duration of Response (DOR)(Up to approximately 36 months)
- Progression-free survival (PFS)(Up to approximately 36 months)
- Time to treatment failure (TTF)(Up to approximately 36 months)
- Overall survival (OS)(Up to approximately 36 months)
- SLV-154 administration(Through the duration of treatment, up to approximately 18 months)
- Evaluation of use of concomitant medications(Through the duration of treatment, up to approximately 18 months)
- Immunogenicity(Varying timepoints through the duration of treatment, up to approximately 18 months)
- 4-month progression-free survival (PFS4)(Up to approximately 36 months)
- 6-month progression-free survival (PFS6)(Up to approximately 36 months)
- Disease benefit ratio (DBR)(Up to approximately 36 months)
- Progression free survival (PFS)(Up to approximately 36 months)
- Duration of disease benefit (DDB)(Up to approximately 36 months)
- Percent change in tumor dimensions(Up to approximately 36 months)