A Phase 1/1b First-in-human Dose Escalation and Expansion Study for the Evaluation of Safety, Pharmacokinetics, Pharmacodynamics, and Anti-tumor Activity of SAR439459 Administered Intravenously as Monotherapy and in Combination With Cemiplimab in Adult Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Sanofi
- 入组人数
- 161
- 试验地点
- 34
- 主要终点
- Incidence of Dose Limiting Toxicities (DLTs)
研究概览
简要总结
Primary Objectives:
Dose escalation (Part 1)
Part 1A (SAR439459 monotherapy)
- To determine the maximum tolerated dose (MTD) and/or maximum administered dose (MAD) of SAR439459 when administered intravenously as monotherapy in adult patients with advanced solid tumors.
Part 1B (SAR439459 and cemiplimab combination therapy)
- To determine the MTD and/or MAD of SAR439459 administered intravenously in combination with cemiplimab administered intravenously in adult patients with advanced solid tumors.
Dose expansion (Part 2)
Part 2A (SAR439459 monotherapy)
- To determine optimal dose of SAR439459 administered intravenously in adult patients with advanced melanoma who have failed a prior therapy based on anti-PD-1 (programmed cell death-1) or anti-PD-L1.
Part 2B (SAR439459 and cemiplimab combination therapy)
- To determine the objective response rate (ORR) of SAR439459 in combination with cemiplimab in adult patients with selected advanced solid tumors by evaluation of antitumor response according to Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1).
Secondary Objectives:
- Pharmacokinetic (PK) profile SAR439459 monotherapy and combined with cemiplimab, PK profile of cemiplimab combined with SAR439459.
- Immunogenicity of SAR439459 monotherapy and combined with cemiplimab.
Dose escalation (Part 1)
- Overall safety/tolerability profile of SAR439459 monotherapy and combined with cemiplimab.
- Preliminary recommended phase 2 dose (pRP2D) of SAR439459 as monotherapy or combined with cemiplimab.
Dose expansion (Part 2)
- Progression free survival (PFS), time to progression (TTP), ORR, and safety of SAR439459 as monotherapy and PFS, TTP, duration of response (DOR), disease control rate (DCR) and safety in combination with cemiplimab.
- To confirm the optimal dose of SAR439459 administered in combination with cemiplimab.
详细描述
The duration of the study for an individual patient will start from the signature of the main informed consent and include a screening period of up to 4 weeks (28 days), a treatment period of at least 1 or 2 cycles (21 or 14 days per cycle, respectively), an end-of-treatment visit at least 30 days following the last administration of study drug (or until the patient receives another anticancer therapy, whichever is earlier), and a follow-up visit 3 months after treatment discontinuation and every 3 months following, until disease progression, or initiation of another antitumor treatment, or death, whichever is earlier. For the urothelial cancer cohort in Part 2B, follow-up visits will occur every 3 months until death, study cut-off date, or upon cancellation of Survival follow-up at the discretion of the Sponsor at any prior timepoint. For the overall survival analysis (approximately 12 months after last patient first dose), whichever comes first.
Patients who have no disease progression, and continue to benefit from the study drug(s), will be allowed to continue treatment beyond the common study end-date at their assigned dose unless the study is terminated by the Sponsor. The expected enrollment period is approximately 42 months.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Dose Expansion SAR439459 monotherapy
SAR439459 administered intravenously every 3 weeks in a 21-day cycle with the previously determined recommended doses as the patients will be randomized to 2 different doses
干预措施: SAR439459 (Biological)
Dose Escalation SAR439459 monotherapy
SAR439459 administered intravenously every 2 weeks in a 14-day cycle with escalating doses
干预措施: SAR439459 (Biological)
Dose Escalation SAR439459 + cemiplimab combination
SAR439459 + cemiplimab combination administered intravenously every 2 weeks in a 14-day cycle or every 3 weeks in a 21-day cycle with escalating SAR439459 doses and cemiplimab
干预措施: SAR439459 (Biological)
Dose Escalation SAR439459 + cemiplimab combination
SAR439459 + cemiplimab combination administered intravenously every 2 weeks in a 14-day cycle or every 3 weeks in a 21-day cycle with escalating SAR439459 doses and cemiplimab
干预措施: Cemiplimab REGN2810 (Drug)
Dose Expansion SAR439459 + cemiplimab combination
SAR439459 + cemiplimab combination administered intravenously every 3 weeks in a 21-day cycle with previously determined SAR439459 doses and cemiplimab
干预措施: SAR439459 (Biological)
Dose Expansion SAR439459 + cemiplimab combination
SAR439459 + cemiplimab combination administered intravenously every 3 weeks in a 21-day cycle with previously determined SAR439459 doses and cemiplimab
干预措施: Cemiplimab REGN2810 (Drug)
结局指标
主要结局
Incidence of Dose Limiting Toxicities (DLTs)
时间窗: Through the end of 1 or 2 cycles, total duration up to 6 weeks (for Part 1A each cycle is 2 weeks; for Part 1B each cycle is 2 or 3 weeks)
Incidence of DLTs at Cycle 1 and/or 2 in Parts 1A and 1B.
Objective Response Rate (ORR) for Part 2B
时间窗: Continuous throughout study assessment (up to approximately 1 year)
Efficacy as documented by ORR will be assessed by evaluation of antitumor response information according to RECIST 1.1 (Part 2B).
次要结局
- Immunogenicity evaluation(Up to approximately 1 year)
- Overall safety profile(Continuous throughout study assessment (up to approximately 1 year))
- Progression free survival (PFS)(Continuous throughout study assessment (up to approximately 1 year))
- Time to progression (TTP)(Continuous throughout study assessment (up to approximately 1 year))
- Objective Response Rate (ORR) Part 2A(Continuous throughout study assessment (up to approximately 1 year))
- Duration of response Part 2B(Continuous throughout study assessment (up to approximately 1 year))
- Disease Control Rate Part 2B(Continuous throughout study assessment (up to approximately 1 year))
- Cmax for SAR439459 and for cemiplimab(Cycle 1, Day 1 to Day 15 or to Day 22)
- AUC0-tau for SAR439459 and for cemiplimab(Cycle 1, Day 1 to Day 15 or to Day 22)
- AUC for SAR439459(Cycle 1, Day 1 to Day 15 or to Day 22)
- t1/2z for SAR439459(Cycle 1, Day 1 to Day 15 or to Day 22)
- CL for SAR439459(Cycle 1, Day 1 to Day 15 or to Day 22)
- Vss for SAR439459(Cycle 1, Day 1 to Day 15 or to Day 22)