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Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT03871348
Other study ID # TED15297
Secondary ID U1111-1205-11762
Status Terminated
Phase Phase 1
First received
Last updated
Start date January 3, 2019
Est. completion date February 21, 2024

Study information

Verified date March 2024
Source Sanofi
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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 information / eligibility

Status Terminated
Enrollment 77
Est. completion date February 21, 2024
Est. primary completion date July 25, 2022
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
SAR441000
Pharmaceutical form: concentrate for solution for injection Route of administration: intratumoral
Cemiplimab REGN2810
Pharmaceutical form: solution for injection Route of administration: intravenous

Locations

Country Name City State
Belgium Investigational Site Number : 0560003 Gent
Belgium Investigational Site Number : 0560002 Leuven
Belgium Investigational Site Number : 0560001 Sint-Lambrechts-Woluwe
France Investigational Site Number : 2500004 Marseille
France Investigational Site Number : 2500002 Paris
France Investigational Site Number : 2500001 Villejuif
Germany Investigational Site Number : 2760005 Hamburg
Germany Investigational Site Number : 2760004 Heidelberg
Germany Investigational Site Number : 2760001 Mainz
Germany Investigational Site Number : 2760003 Mannheim
Germany Investigational Site Number : 2760006 Tübingen
Netherlands Investigational Site Number : 5280002 Nijmegen
Netherlands Investigational Site Number : 5280001 Rotterdam
Spain Investigational Site Number : 7240004 Barcelona Barcelona [Barcelona]
Spain Investigational Site Number : 7240001 Pamplona Navarra
Spain Investigational Site Number : 7240005 Pamplona Navarra
Spain Investigational Site Number : 7240002 Valencia
United States 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

Sponsors (2)

Lead Sponsor Collaborator
Sanofi BioNTech RNA Pharmaceuticals GmbH

Countries where clinical trial is conducted

United States,  Belgium,  France,  Germany,  Netherlands,  Spain, 

Outcome

Type Measure Description Time frame Safety issue
Primary For dose escalation: Incidence of Dose Limiting Toxicities (DLTs) (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 Cycle 1; Cycle = 28 days for monotherapy
Primary For dose escalation: Incidence of Dose Limiting Toxicities (DLTs) (Combination therapy) 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 Cycle 1 Day 1 to Cycle 2 Day 8; Cycle = 21 days for combination therapy; overall assessment = 28 days
Primary For dose escalation: Maximum tolerated dose (MTD) of SAR441000 (Monotherapy) MTD of SAR441000 as monotherapy, determined during Cycle 1 of dose escalation phase End of Dose Escalation phase (ie, End of Cycle 1 for last patient); Cycle = 28 days for monotherapy
Primary For dose escalation: Maximum tolerated dose (MTD) of SAR441000 (Combination therapy) MTD of SAR441000, in combination with cemiplimab, determined during period from Cycle 1 Day 1 to Cycle 2 Day 8 in dose escalation phase 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
Primary Adverse Events Incidence of Treatment Emergent Adverse Events (TEAE) during dose escalation phase Up to end of treatment (Estimated median duration=12 months)
Primary For Expansion: Objective Response Rate (ORR) Assessment of overall response rate using standard imaging and RECIST 1.1 criteria Estimated median duration = 12 months
Secondary Assessment of Pharmacokinetic (PK) parameter for SAR441000 (Cmax) (Monotherapy) Maximum plasma concentration (Cmax) of SAR4410000 as monotherapy observed over the dosing interval Cycle 1 Week 1 and Cycle 3 Week 1 (in all patients); Cycle duration is 28 days for monotherapy
Secondary Assessment of Pharmacokinetic (PK) parameter for SAR441000 (Cmax) (Combination therapy) Maximum plasma concentration (Cmax) of SAR4410000 in combination with cemiplimab observed over the dosing interval Cycle 1 Week 1 and Cycle 3 Week 1 (in all patients); Cycle duration is 21 days for combination therapy
Secondary Assessment of PK parameter for SAR441000 (AUC) (Monotherapy) Area under the plasma concentration versus time curve (AUC) of SAR441000 as monotherapy over the dosing interval Cycle 1 Week 1 and Cycle 3 Week 1 (in all patients); Cycle duration is 28 days for monotherapy
Secondary Assessment of PK parameter for SAR441000 (AUC) (Combination therapy) Area under the plasma concentration versus time curve (AUC) of SAR441000 in combination with cemiplimab over the dosing interval Cycle 1 Week 1 and Cycle 3 Week 1 (in all patients); Cycle duration is 21 days for combination therapy
Secondary Assessment of PK parameter (Ctrough) for SAR441000 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 Baseline to End of Treatment (Estimated median duration of 12 months)
Secondary Assessment of PK parameter for cemiplimab (Cmax) Maximum plasma concentration of cemiplimab in combination with SAR441000, observed over the dosing interval Cycle 1; Cycle duration is 21 days
Secondary Assessment of PK parameter of cemiplimab (AUC) Area under the plasma concentration versus time curve of cemiplimab in combination with SAR441000 over the dosing interval Cycle 1; Cycle duration is 21 days
Secondary Assessment of PK parameter for cemiplimab (Ctrough) Trough plasma concentration of cemiplimab in combination with SAR441000, observed just before treatment administration during repeated dosing Baseline to End of Treatment (Estimated median duration of 12 months)
Secondary Immunogenicity of SAR441000 and cemiplimab Incidence of anti-drug antibody (ADA) positive patients for immunogenicity Baseline to End of Study (Estimated median duration of 12 months)
Secondary DCR Disease Control Rate (DCR) with SAR441000 in combination with cemiplimab. DCR is sum of Complete Response + Partial Response + Stable Disease Baseline to End of Study (Estimated median duration of 12 months)
Secondary DoR Duration of Response (DoR) with SAR441000 in combination with cemiplimab. DoR is time from initial response to the first documented tumor progression Baseline to End of Study (Estimated median duration of 12 months)
Secondary Progression Free Survival (PFS) Time from first drug administration to the first documented tumor progression or death from any cause, whichever comes first Baseline to End of Study (Estimated median duration of 12 months)
Secondary Incidence of Treatment Emergent Adverse Events (TEAE) during dose expansion phase Incidence of Adverse Events (AE)/ Serious AE (SAE) / Laboratory abnormalities considered to be adverse events Baseline to End of Treatment (Estimated median duration of 12 months)
Secondary Recommended dose of SAR441000 for expansion phase (Combination therapy) 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 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
Secondary For Dose Expansion: Objective Response Rate (ORR) Assessment of overall response rate using standard imaging by RECIST 1.1 and iRECIST criteria Estimated median duration of 12 months
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