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
Trial Snapshot
- Phase
- Phase 1
- Status
- Terminated
- Sponsor
- Sanofi
- Enrollment
- 77
- Locations
- 19
- Primary Endpoint
- For dose escalation: Incidence of Dose Limiting Toxicities (DLTs) (Combination therapy)
Study Overview
Brief Summary
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.
Detailed Description
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.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
SAR441000 Dose Escalation Phase
SAR441000 will be administered as intratumoral injection as monotherapy in patients with solid tumors over a 28-day cycle
Intervention: 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
Intervention: 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
Intervention: 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
Intervention: 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
Intervention: 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
Intervention: 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
Intervention: 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
Intervention: 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
Intervention: 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
Intervention: 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
Intervention: Cemiplimab REGN2810 (Drug)
Outcomes
Primary Outcomes
For dose escalation: Incidence of Dose Limiting Toxicities (DLTs) (Combination therapy)
Time Frame: 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)
Time Frame: 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
Time Frame: 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)
Time Frame: 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)
Time Frame: 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)
Time Frame: 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
Secondary Outcomes
- 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)