A Phase 1/2, Open-Label, Dose-Escalation and Expansion Study of SBT6290 Alone and in Combination With PD-(L)1 Inhibitors in Subjects With Advanced Solid Tumors Associated With Nectin-4 Expression
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 发起方
- 主要终点
- Number of Participants With Dose Limiting Toxicities: Part 1 and Part 3
研究概览
简要总结
This is a first-in-human, open-label, multicenter, dose-escalation and expansion study designed to investigate SBT6290 administered alone and in combination with pembrolizumab in advanced solid tumors associated with Nectin-4 expression.
详细描述
This is a first-in-human study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, immunogenicity, and preliminary antitumor activity of SBT6290 administered subcutaneously (SC) as a monotherapy and in combination with pembrolizumab in solid tumors associated with Nectin-4 expression. There are 4 parts to this study:
- Part 1: A dose escalation of SBT6290 monotherapy
- Part 2: Tumor-specific expansion cohorts evaluating SBT6290 monotherapy administered at the recommended phase 2 dose (RP2D) identified in Part 1
- Part 3: A dose escalation of SBT6290 in combination with pembrolizumab
- Part 4: An expansion cohort of SBT6290 in combination with pembrolizumab administered at the RP2D identified in Part 3 for the combination
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
- •Locally advanced or metastatic solid tumors associated associated with Nectin-4 expression (locally advanced or metastatic urothelial carcinoma, TNBC, NSCLC, SCCHN, and HR+/HER2- negative breast cancer)
- •Measurable disease per the the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 criteria
- •Tumor lesion amenable for biopsy available to submit for retrospective baseline testing of Nectin-4; archived tumor tissue may be acceptable depending upon study Part detailed criteria
- •ECOG Performance Status of 0 or 1
- •Adequate organ and marrow function Note: Other protocol-defined inclusion/exclusion criteria may apply.
排除标准
- •History of allergic reactions to certain components of study treatments
- •Untreated brain metastases
- •Currently active (or history of) autoimmune disease
- •Taking the equivalent of >10 mg / day of prednisone
- •Uncontrolled or clinically significant interstitial lung disease (ILD)
- •History of ongoing, uncontrolled, symptomatic eye disorders requiring intervention or associated with marked visual field defects or limiting age-appropriate instrumental activities of daily living
- •HIV infection, active hepatitis B or hepatitis C infection Note: Other protocol-defined inclusion/exclusion criteria may apply.
研究组 & 干预措施
Part 1: SBT6290
SBT6290 every 3 weeks
干预措施: SBT6290 (Drug)
Part 2: SBT6290
SBT6290 every 3 weeks
干预措施: SBT6290 (Drug)
Part 3: SBT6290 + pembrolizumab
SBT6290 plus pembrolizumab every 3 weeks
干预措施: SBT6290 (Drug)
Part 3: SBT6290 + pembrolizumab
SBT6290 plus pembrolizumab every 3 weeks
干预措施: pembrolizumab (Drug)
Part 4: SBT6290 + pembrolizumab
SBT6290 plus pembrolizumab every 3 weeks
干预措施: SBT6290 (Drug)
Part 4: SBT6290 + pembrolizumab
SBT6290 plus pembrolizumab every 3 weeks
干预措施: pembrolizumab (Drug)
结局指标
主要结局
Number of Participants With Dose Limiting Toxicities: Part 1 and Part 3
时间窗: Up to 28 days after the first dose of SBT6290
Severity of treatment-emergent adverse events as assessed by the NCI CTCAE Version 5.0.
Number of Participants With an Objective Response Rate: Part 2 and Part 4
时间窗: From enrollment to confirmed response, up to 1 year
Complete response and partial response as assessed by RECIST Version 1.1 Criteria.
Number of Participants With Treatment-emergent Adverse Events: All Parts
时间窗: From enrollment to 30 days after the last dose of SBT6290, up to 2 years
Severity of treatment-emergent adverse events as assessed by the NCI CTCAE Version 5.0.
Duration of Response for Participants With an Objective Response Rate: Part 2 and Part 4
时间窗: From enrollment until the date of first documented progression or date of death from any cause, whichever occurs first, assessed up to 3 years
Complete response and partial response as assessed by RECIST Version 1.1 Criteria.
次要结局
- Rate of Disease Control for Participants: All Parts(Up to at least 6 months after the first dose of SBT6290)
- Number of Participants With an Objective Response Rate: Part 1 and Part 3(From enrollment to confirmed response, up to 1 year)
- Incidence of SBT6290 Antidrug Antibodies (ADA): All Parts(Immediately before and after SBT6290 doses for up to 2 years)
- Duration of Response for Participants With an Objective Response Rate: Part 1 and Part 3(From enrollment until the date of first documented progression or date of death from any cause, whichever occurs first, assessed up to 3 years)
- Progression-free Survival: Part 2(From first dose of SBT6290 until the date of first documented progression or date of death from any cause, whichever occurs first, assessed up to 3 years)
- Estimates of Selected PK Parameters for SBT6290: All Parts(Immediately before and after SBT6290 doses up to 2 years)