A Phase 1 First-in-Human Dose Escalation and Expansion Study for the Evaluation of Safety, Pharmacokinetics, Pharmacodynamics and Anti-tumor Activity of SAR441000 Administered Intratumorally as Monotherapy and in Combination With Cemiplimab in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- Sanofi
- 入组人数
- 77
- 试验地点
- 19
- 主要终点
- For dose escalation: Incidence of Dose Limiting Toxicities (DLTs) (Combination therapy)
研究概览
简要总结
Primary Objectives:
- Dose Escalation: To determine maximum tolerated dose (MTD) or maximum administered dose (MAD) and overall safety and tolerability profile of SAR441000 when administered intratumorally as monotherapy and in combination with cemiplimab in patients who have no alternative standard treatment options.
- Dose Expansion (Combination): To determine the objective response rate of SAR441000 administered intratumorally in combination with cemiplimab in patients with melanoma, cutaneous squamous cell carcinoma or head and neck squamous cell carcinoma.
Secondary Objectives:
- To characterize the pharmacokinetic (PK) profile of SAR441000 administered as monotherapy and in combination with cemiplimab.
- To assess the immunogenicity of SAR441000.
- To characterize the safety of SAR441000 when administered intratumorally in combination with cemiplimab.
- To determine the disease control rate (DCR), duration of response (DoR) and progression free survival (PFS) of SAR441000.
- To determine the recommended dose of SAR441000 for the expansion phase.
详细描述
The expected duration of treatment for patients who benefit from study intervention may vary, based on progression date. Median expected duration of study per patient is estimated as 9 months in monotherapy and 12 months in combination therapy.
The maximum treatment duration for non-progressive patients is up to 2 years.
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
SAR441000 Dose Escalation Phase
SAR441000 will be administered as intratumoral injection as monotherapy in patients with solid tumors over a 28-day cycle
干预措施: SAR441000 (Drug)
SAR441000 + cemiplimab - Dose Escalation Phase
SAR441000 will be administered as intratumoral injection in patients with solid tumors in combination with cemiplimab over a 21-day cycle
干预措施: SAR441000 (Drug)
SAR441000 + cemiplimab - Dose Escalation Phase
SAR441000 will be administered as intratumoral injection in patients with solid tumors in combination with cemiplimab over a 21-day cycle
干预措施: Cemiplimab REGN2810 (Drug)
SAR441000 + cemiplimab Expansion Melanoma, anti-PD-1 failure
SAR441000 will be administered intratumorally at the determined recommended dose in combination with cemiplimab to patients with advanced melanoma who have failed anti-PD-1/PD-L1 therapy. Treatment is administered over a 21-day cycle
干预措施: SAR441000 (Drug)
SAR441000 + cemiplimab Expansion Melanoma, anti-PD-1 failure
SAR441000 will be administered intratumorally at the determined recommended dose in combination with cemiplimab to patients with advanced melanoma who have failed anti-PD-1/PD-L1 therapy. Treatment is administered over a 21-day cycle
干预措施: Cemiplimab REGN2810 (Drug)
SAR441000 + cemiplimab Expansion Melanoma, anti-PD-1 naive
SAR441000 will be administered intratumorally at the determined recommended dose in combination with cemiplimab to patients with advanced anti-PD-1/PD-L1 naïve melanoma over a 21-day cycle
干预措施: SAR441000 (Drug)
SAR441000 + cemiplimab Expansion Melanoma, anti-PD-1 naive
SAR441000 will be administered intratumorally at the determined recommended dose in combination with cemiplimab to patients with advanced anti-PD-1/PD-L1 naïve melanoma over a 21-day cycle
干预措施: Cemiplimab REGN2810 (Drug)
SAR441000 + cemiplimab Expansion CSCC, anti-PD-1 naive
SAR441000 will be administered intratumorally at the determined recommended dose in combination with cemiplimab to patients with advanced anti-PD-1/PD-L1 naïve Cutaneous Squamous Cell Carcinoma (CSCC) over a 21-day cycle
干预措施: SAR441000 (Drug)
SAR441000 + cemiplimab Expansion CSCC, anti-PD-1 naive
SAR441000 will be administered intratumorally at the determined recommended dose in combination with cemiplimab to patients with advanced anti-PD-1/PD-L1 naïve Cutaneous Squamous Cell Carcinoma (CSCC) over a 21-day cycle
干预措施: Cemiplimab REGN2810 (Drug)
SAR441000 + cemiplimab Expansion HNSCC, anti-PD-1 naive
SAR441000 will be administered intratumorally at the determined recommended dose in combination with cemiplimab to patients with advanced anti-PD-1/PD-L1 naïve Head and Neck Squamous Cell Cancer (HNSCC) over a 21-day cycle
干预措施: SAR441000 (Drug)
SAR441000 + cemiplimab Expansion HNSCC, anti-PD-1 naive
SAR441000 will be administered intratumorally at the determined recommended dose in combination with cemiplimab to patients with advanced anti-PD-1/PD-L1 naïve Head and Neck Squamous Cell Cancer (HNSCC) over a 21-day cycle
干预措施: Cemiplimab REGN2810 (Drug)
结局指标
主要结局
For dose escalation: Incidence of Dose Limiting Toxicities (DLTs) (Combination therapy)
时间窗: Cycle 1 Day 1 to Cycle 2 Day 8; Cycle = 21 days for combination therapy; overall assessment = 28 days
Incidence of DLTs during period from Cycle 1 Day 1 to Cycle 2 Day 8 (SAR441000 + cemiplimab combination therapy), assessed as the occurrence of AE, satisfying protocol defined DLT criteria, using NCI-CTCAE version 5.0 whether related or not to the study treatment in the absence of clear evidence to the contrary, and if not related to a disease progression
For dose escalation: Maximum tolerated dose (MTD) of SAR441000 (Combination therapy)
时间窗: End of Dose Escalation Phase (ie, End of Cycle 1 Day 1 to Cycle 2 Day 8 for last patient); Cycle = 21 days for combination; overall assesment = 28 days
MTD of SAR441000, in combination with cemiplimab, determined during period from Cycle 1 Day 1 to Cycle 2 Day 8 in dose escalation phase
Adverse Events
时间窗: Up to end of treatment (Estimated median duration=12 months)
Incidence of Treatment Emergent Adverse Events (TEAE) during dose escalation phase
For Expansion: Objective Response Rate (ORR)
时间窗: Estimated median duration = 12 months
Assessment of overall response rate using standard imaging and RECIST 1.1 criteria
For dose escalation: Maximum tolerated dose (MTD) of SAR441000 (Monotherapy)
时间窗: End of Dose Escalation phase (ie, End of Cycle 1 for last patient); Cycle = 28 days for monotherapy
MTD of SAR441000 as monotherapy, determined during Cycle 1 of dose escalation phase
For dose escalation: Incidence of Dose Limiting Toxicities (DLTs) (Monotherapy)
时间窗: Cycle 1; Cycle = 28 days for monotherapy
Incidence of DLTs at Cycle 1 (SAR441000 monotherapy), assessed as the occurrence of AE, satisfying protocol defined DLT criteria, using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0 whether related or not to the study treatment in the absence of clear evidence to the contrary, and if not related to a disease progression
次要结局
- Assessment of PK parameter (Ctrough) for SAR441000(Baseline to End of Treatment (Estimated median duration of 12 months))
- DCR(Baseline to End of Study (Estimated median duration of 12 months))
- Assessment of PK parameter for SAR441000 (AUC) (Combination therapy)(Cycle 1 Week 1 and Cycle 3 Week 1 (in all patients); Cycle duration is 21 days for combination therapy)
- Progression Free Survival (PFS)(Baseline to End of Study (Estimated median duration of 12 months))
- Recommended dose of SAR441000 for expansion phase (Combination therapy)(End of Dose Escalation Phase (ie, End of Cycle 1 Day 1 to Cycle 2 Day 8 for last patient); Cycle = 21 days for combination; overall assesment = 28 days)
- Assessment of Pharmacokinetic (PK) parameter for SAR441000 (Cmax) (Monotherapy)(Cycle 1 Week 1 and Cycle 3 Week 1 (in all patients); Cycle duration is 28 days for monotherapy)
- Assessment of PK parameter for SAR441000 (AUC) (Monotherapy)(Cycle 1 Week 1 and Cycle 3 Week 1 (in all patients); Cycle duration is 28 days for monotherapy)
- Assessment of PK parameter for cemiplimab (Cmax)(Cycle 1; Cycle duration is 21 days)
- Assessment of PK parameter of cemiplimab (AUC)(Cycle 1; Cycle duration is 21 days)
- Assessment of PK parameter for cemiplimab (Ctrough)(Baseline to End of Treatment (Estimated median duration of 12 months))
- Immunogenicity of SAR441000 and cemiplimab(Baseline to End of Study (Estimated median duration of 12 months))
- Assessment of Pharmacokinetic (PK) parameter for SAR441000 (Cmax) (Combination therapy)(Cycle 1 Week 1 and Cycle 3 Week 1 (in all patients); Cycle duration is 21 days for combination therapy)
- DoR(Baseline to End of Study (Estimated median duration of 12 months))
- Incidence of Treatment Emergent Adverse Events (TEAE) during dose expansion phase(Baseline to End of Treatment (Estimated median duration of 12 months))
- For Dose Expansion: Objective Response Rate (ORR)(Estimated median duration of 12 months)