A First-in-Human Dose Escalation and Expansion Study to Evaluate Intratumoral Administration of SAR441000 as Monotherapy and in Combination With Cemiplimab in Patients With Advanced Solid Tumors
- Registration Number
- NCT03871348
- Lead Sponsor
- Sanofi
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 77
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description SAR441000 + cemiplimab Expansion Melanoma, anti-PD-1 failure Cemiplimab REGN2810 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 SAR441000 + cemiplimab Expansion CSCC, anti-PD-1 naive Cemiplimab REGN2810 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 SAR441000 Dose Escalation Phase SAR441000 SAR441000 will be administered as intratumoral injection as monotherapy in patients with solid tumors over a 28-day cycle SAR441000 + cemiplimab - Dose Escalation Phase Cemiplimab REGN2810 SAR441000 will be administered as intratumoral injection in patients with solid tumors in combination with cemiplimab over a 21-day cycle SAR441000 + cemiplimab - Dose Escalation Phase SAR441000 SAR441000 will be administered as intratumoral injection in patients with solid tumors in combination with cemiplimab over a 21-day cycle SAR441000 + cemiplimab Expansion Melanoma, anti-PD-1 failure SAR441000 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 SAR441000 + cemiplimab Expansion Melanoma, anti-PD-1 naive Cemiplimab REGN2810 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 SAR441000 + cemiplimab Expansion HNSCC, anti-PD-1 naive Cemiplimab REGN2810 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 SAR441000 + cemiplimab Expansion CSCC, anti-PD-1 naive SAR441000 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 SAR441000 + cemiplimab Expansion HNSCC, anti-PD-1 naive SAR441000 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 SAR441000 + cemiplimab Expansion Melanoma, anti-PD-1 naive SAR441000 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
- Primary Outcome Measures
Name Time Method For dose escalation: Incidence of Dose Limiting Toxicities (DLTs) (Combination therapy) 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) 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 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) 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) 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) 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 Outcome Measures
Name Time Method Assessment of PK parameter (Ctrough) for SAR441000 Baseline to End of Treatment (Estimated median duration of 12 months) Trough Plasma Concentration (Ctrough) of SAR441000 as monotherapy and in combination with cemiplimab. It is defined as plasma concentration observed just before treatment administration during repeated dosing
DCR Baseline to End of Study (Estimated median duration of 12 months) Disease Control Rate (DCR) with SAR441000 in combination with cemiplimab. DCR is sum of Complete Response + Partial Response + Stable Disease
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 Area under the plasma concentration versus time curve (AUC) of SAR441000 in combination with cemiplimab over the dosing interval
Progression Free Survival (PFS) Baseline to End of Study (Estimated median duration of 12 months) Time from first drug administration to the first documented tumor progression or death from any cause, whichever comes first
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 SAR441000 dose for administration in combination with cemiplimab selected for expansion phase based on MTD/MAD by the Bayesian model, the overall safety, activity and PK/PDy data
DoR Baseline to End of Study (Estimated median duration of 12 months) Duration of Response (DoR) with SAR441000 in combination with cemiplimab. DoR is time from initial response to the first documented tumor progression
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 Maximum plasma concentration (Cmax) of SAR4410000 in combination with cemiplimab observed over the dosing interval
Incidence of Treatment Emergent Adverse Events (TEAE) during dose expansion phase Baseline to End of Treatment (Estimated median duration of 12 months) Incidence of Adverse Events (AE)/ Serious AE (SAE) / Laboratory abnormalities considered to be adverse events
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 Maximum plasma concentration (Cmax) of SAR4410000 as monotherapy observed over the dosing interval
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 Area under the plasma concentration versus time curve (AUC) of SAR441000 as monotherapy over the dosing interval
Assessment of PK parameter for cemiplimab (Cmax) Cycle 1; Cycle duration is 21 days Maximum plasma concentration of cemiplimab in combination with SAR441000, observed over the dosing interval
Assessment of PK parameter of cemiplimab (AUC) Cycle 1; Cycle duration is 21 days Area under the plasma concentration versus time curve of cemiplimab in combination with SAR441000 over the dosing interval
Assessment of PK parameter for cemiplimab (Ctrough) Baseline to End of Treatment (Estimated median duration of 12 months) Trough plasma concentration of cemiplimab in combination with SAR441000, observed just before treatment administration during repeated dosing
Immunogenicity of SAR441000 and cemiplimab Baseline to End of Study (Estimated median duration of 12 months) Incidence of anti-drug antibody (ADA) positive patients for immunogenicity
For Dose Expansion: Objective Response Rate (ORR) Estimated median duration of 12 months Assessment of overall response rate using standard imaging by RECIST 1.1 and iRECIST criteria
Trial Locations
- Locations (20)
Dana Farber Cancer Institute Site Number : 8400003
🇺🇸Boston, Massachusetts, United States
Cleveland Clinic Foundation Site Number : 8400007
🇺🇸Cleveland, Ohio, United States
~University of Texas - MD Anderson Cancer Center Site Number : 8400002
🇺🇸Houston, Texas, United States
Investigational Site Number : 0560003
🇧🇪Gent, Belgium
Investigational Site Number : 0560002
🇧🇪Leuven, Belgium
Investigational Site Number : 0560001
🇧🇪Sint-Lambrechts-Woluwe, Belgium
Investigational Site Number : 2500004
🇫🇷Marseille, France
Investigational Site Number : 2500001
🇫🇷Villejuif, France
Investigational Site Number : 2500002
🇫🇷Paris, France
Investigational Site Number : 2760003
🇩🇪Mannheim, Germany
Investigational Site Number : 2760005
🇩🇪Hamburg, Germany
Investigational Site Number : 2760004
🇩🇪Heidelberg, Germany
Investigational Site Number : 2760001
🇩🇪Mainz, Germany
Investigational Site Number : 2760006
🇩🇪Tübingen, Germany
Investigational Site Number : 5280002
🇳🇱Nijmegen, Netherlands
Investigational Site Number : 7240001
🇪🇸Pamplona, Navarra, Spain
Investigational Site Number : 5280001
🇳🇱Rotterdam, Netherlands
Investigational Site Number : 7240005
🇪🇸Pamplona, Navarra, Spain
Investigational Site Number : 7240002
🇪🇸Valencia, Spain
Investigational Site Number : 7240004
🇪🇸Barcelona, Barcelona [Barcelona], Spain