Description:
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.
Title
- Brief Title: 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
- Official Title: 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
Clinical Trial IDs
- ORG STUDY ID:
TED15297
- SECONDARY ID:
2017-004766-94
- SECONDARY ID:
U1111-1205-1176
- NCT ID:
NCT03871348
Conditions
Interventions
Drug | Synonyms | Arms |
---|
SAR441000 | | SAR441000 + cemiplimab - Dose Escalation Phase |
Cemiplimab REGN2810 | | SAR441000 + cemiplimab - Dose Escalation Phase |
Purpose
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.
Trial Arms
Name | Type | Description | Interventions |
---|
SAR441000 Dose Escalation Phase | Experimental | SAR441000 will be administered as intratumoral injection as monotherapy in patients with solid tumors over a 28-day cycle | |
SAR441000 + cemiplimab - Dose Escalation Phase | Experimental | SAR441000 will be administered as intratumoral injection in patients with solid tumors in combination with cemiplimab over a 21-day cycle | - SAR441000
- Cemiplimab REGN2810
|
SAR441000 + cemiplimab Expansion Melanoma, anti-PD-1 failure | Experimental | 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 REGN2810
|
SAR441000 + cemiplimab Expansion Melanoma, anti-PD-1 naive | Experimental | 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 REGN2810
|
SAR441000 + cemiplimab Expansion CSCC, anti-PD-1 naive | Experimental | 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 REGN2810
|
SAR441000 + cemiplimab Expansion HNSCC, anti-PD-1 naive | Experimental | 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 REGN2810
|
Eligibility Criteria
Inclusion criteria:
- At least 18 years of age
- Advanced solid tumors including lymphomas for which no standard alternative therapy is
available (escalation phase).
- Advanced melanoma (Stage IIIB-C or Stage IV, anti-PD-1/PD-L1 treated or not) or
anti-PD-1/PD-L1 not treated advanced Head and Neck Squamous Cell Cancer or
anti-PD-1/PD-L1 not treated Advanced Cutaneous Squamous Cell Cancer where no other
alternative treatment option exists (expansion phases).
- Minimum 3 lesions enrollment.
- Injectable disease (i.e., suitable for direct intratumoral injection based on the dose
level volume of each cohort and cumulative lesion size; according to the
investigator's judgement).
- A lesion amenable for additional tumor biopsy.
- Patients with measurable disease according to the Response Evaluation Criteria in
Solid Tumors (RECIST) 1.1 criteria.
- Life expectancy more than 3 months.
- Willingness to provide mandatory tumor biopsy.
- Male and female patients who agree to use effective contraceptive methods.
- Signed informed consent.
Exclusion criteria:
- Eastern Cooperative Oncology Group (ECOG) performance score >1.
- Significant and uncontrolled concomitant illness that would adversely affect the
patient's participation in the study.
- Any prior organ transplantation.
- History within the last 5 years of an invasive malignancy other than the one treated
in this study, with the exception of resected basal or squamous-cell skin cancer or
carcinoma, in situ of cervix or other local tumors considered cured by local
treatment.
- History of unresolved viral hepatitis; systemic immune suppression including acquired
immunodeficiency syndrome (AIDS) related illnesses or human immunodeficiency virus
(HIV) disease requiring antiretroviral treatment.
- Prior splenectomy.
- New and progressive brain lesions.
- Poor bone marrow reserve resulting in low blood cell count.
- Poor liver and kidney functions, abnormal coagulation tests.
- Ongoing or recent (within 5 years) evidence of significant autoimmune disease that
required treatment with systemic immunosuppressive treatments.
- Maintenance therapy with prednisolone >7.5 mg/day orally or equivalent during the
study.
- Non-resolution of any prior treatment related toxicity to Grade <2, except alopecia,
vitiligo, fatigue and hypothyroidism controlled with replacement therapies.
- Moderate to severe immune related adverse event to prior immune-modulating agents
within 90 days prior to the first study treatment.
- Central nervous system lymphoma.
- Prior allogeneic hematopoietic stem cell transplantation (HSCT) for patients with
lymphoma.
- Autologous HSCT less than 90 days prior to initiation of study intervention.
The above information is not intended to contain all considerations relevant to a patient's
potential participation in a clinical trial.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | For dose escalation: Incidence of Dose Limiting Toxicities (DLTs) (Monotherapy) |
Time Frame: | Cycle 1; Cycle = 28 days for monotherapy |
Safety Issue: | |
Description: | 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
Measure: | Assessment of Pharmacokinetic (PK) parameter for SAR441000 (Cmax) (Monotherapy) |
Time Frame: | Cycle 1 Week 1 and Cycle 3 Week 1 (in all patients); Cycle duration is 28 days for monotherapy |
Safety Issue: | |
Description: | Maximum plasma concentration (Cmax) of SAR4410000 as monotherapy observed over the dosing interval |
Measure: | Assessment of Pharmacokinetic (PK) parameter for SAR441000 (Cmax) (Combination therapy) |
Time Frame: | Cycle 1 Week 1 and Cycle 3 Week 1 (in all patients); Cycle duration is 21 days for combination therapy |
Safety Issue: | |
Description: | Maximum plasma concentration (Cmax) of SAR4410000 in combination with cemiplimab observed over the dosing interval |
Measure: | Assessment of PK parameter for SAR441000 (AUC) (Monotherapy) |
Time Frame: | Cycle 1 Week 1 and Cycle 3 Week 1 (in all patients); Cycle duration is 28 days for monotherapy |
Safety Issue: | |
Description: | Area under the plasma concentration versus time curve (AUC) of SAR441000 as monotherapy over the dosing interval |
Measure: | Assessment of PK parameter for SAR441000 (AUC) (Combination therapy) |
Time Frame: | Cycle 1 Week 1 and Cycle 3 Week 1 (in all patients); Cycle duration is 21 days for combination therapy |
Safety Issue: | |
Description: | Area under the plasma concentration versus time curve (AUC) of SAR441000 in combination with cemiplimab over the dosing interval |
Measure: | Assessment of PK parameter (Ctrough) for SAR441000 |
Time Frame: | Baseline to End of Treatment (Estimated median duration of 12 months) |
Safety Issue: | |
Description: | 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 |
Measure: | Assessment of PK parameter for cemiplimab (Cmax) |
Time Frame: | Cycle 1; Cycle duration is 21 days |
Safety Issue: | |
Description: | Maximum plasma concentration of cemiplimab in combination with SAR441000, observed over the dosing interval |
Measure: | Assessment of PK parameter of cemiplimab (AUC) |
Time Frame: | Cycle 1; Cycle duration is 21 days |
Safety Issue: | |
Description: | Area under the plasma concentration versus time curve of cemiplimab in combination with SAR441000 over the dosing interval |
Measure: | Assessment of PK parameter for cemiplimab (Ctrough) |
Time Frame: | Baseline to End of Treatment (Estimated median duration of 12 months) |
Safety Issue: | |
Description: | Trough plasma concentration of cemiplimab in combination with SAR441000, observed just before treatment administration during repeated dosing |
Measure: | Immunogenicity of SAR441000 and cemiplimab |
Time Frame: | Baseline to End of Study (Estimated median duration of 12 months) |
Safety Issue: | |
Description: | Incidence of anti-drug antibody (ADA) positive patients for immunogenicity |
Measure: | DCR |
Time Frame: | Baseline to End of Study (Estimated median duration of 12 months) |
Safety Issue: | |
Description: | Disease Control Rate (DCR) with SAR441000 in combination with cemiplimab. DCR is sum of Complete Response + Partial Response + Stable Disease |
Measure: | DoR |
Time Frame: | Baseline to End of Study (Estimated median duration of 12 months) |
Safety Issue: | |
Description: | Duration of Response (DoR) with SAR441000 in combination with cemiplimab. DoR is time from initial response to the first documented tumor progression |
Measure: | Progression Free Survival (PFS) |
Time Frame: | Baseline to End of Study (Estimated median duration of 12 months) |
Safety Issue: | |
Description: | Time from first drug administration to the first documented tumor progression or death from any cause, whichever comes first |
Measure: | Incidence of Treatment Emergent Adverse Events (TEAE) during dose expansion phase |
Time Frame: | Baseline to End of Treatment (Estimated median duration of 12 months) |
Safety Issue: | |
Description: | Incidence of Adverse Events (AE)/ Serious AE (SAE) / Laboratory abnormalities considered to be adverse events |
Measure: | Recommended dose of SAR441000 for expansion phase (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 |
Safety Issue: | |
Description: | 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 |
Measure: | For Dose Expansion: Objective Response Rate (ORR) |
Time Frame: | Estimated median duration of 12 months |
Safety Issue: | |
Description: | Assessment of overall response rate using standard imaging by RECIST 1.1 and iRECIST criteria |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Sanofi |
Last Updated
July 27, 2021