Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03871348
Recruitment Status : Recruiting
First Posted : March 12, 2019
Last Update Posted : March 12, 2019
Sponsor:
Collaborator:
Biontech RNA Pharmaceuticals GmbH
Information provided by (Responsible Party):
Sanofi

Tracking Information
First Submitted Date  ICMJE January 24, 2019
First Posted Date  ICMJE March 12, 2019
Last Update Posted Date March 12, 2019
Actual Study Start Date  ICMJE January 3, 2019
Estimated Primary Completion Date August 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 10, 2019)
  • For dose escalation: Incidence of Dose Limiting Toxicities (DLTs) (Monotherapy) [ Time Frame: Cycle 1; Cycle duration is 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
  • For dose escalation: Incidence of Dose Limiting Toxicities (DLTs) (Combination therapy) [ Time Frame: Cycle 1; Cycle duration is 21 days for combination therapy ]
    Incidence of DLTs at Cycle 1 (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 (Monotherapy) [ Time Frame: End of each Dose Escalation Phase (ie, End of Cycle 1 for last patient treated at dose escalation); Cycle duration is 28 days for monotherapy ]
    MTD of SAR441000 as monotherapy, determined during Cycle 1 of dose escalation phase
  • For dose escalation: Maximum tolerated dose (MTD) of SAR441000 (Combination therapy) [ Time Frame: End of each Dose Escalation Phase (ie, End of Cycle 1 for last patient treated at dose escalation); Cycle duration is 21 days for combination ]
    MTD of SAR441000, in combination with cemiplimab, determined during Cycle 1 of dose escalation phase
  • Adverse Events [ Time Frame: Baseline to End of treatment (Estimated median duration of 12 months) ]
    Incidence of Treatment Emergent Adverse Events (TEAE) during dose escalation phase
  • For Expansion: Objective Response Rate (ORR) [ Time Frame: Estimated median duration of 12 months ]
    Assessment of overall response rate using standard imaging and RECIST 1.1 criteria
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: March 10, 2019)
  • 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 ]
    Maximum plasma concentration (Cmax) of SAR4410000 as monotherapy observed over the dosing interval
  • 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 ]
    Maximum plasma concentration (Cmax) of SAR4410000 in combination with cemiplimab observed over the dosing interval
  • 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 ]
    Area under the plasma concentration versus time curve (AUC) of SAR441000 as monotherapy over the dosing interval
  • 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 ]
    Area under the plasma concentration versus time curve (AUC) of SAR441000 in combination with cemiplimab over the dosing interval
  • Assessment of PK parameter (Ctrough) for SAR441000 [ Time Frame: 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
  • Assessment of PK parameter for cemiplimab (Cmax) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: Baseline to End of Study (Estimated median duration of 12 months) ]
    Incidence of anti-drug antibody (ADA) positive patients for immunogenicity
  • DCR [ Time Frame: Baseline to End of Study (Estimated median duration of 12 months) ]
    Disease Control Rate (DCR) with SAR441000 as monotherapy and in combination with cemiplimab. DCR is sum of Complete Response + Partial Response + Stable Disease
  • DoR [ Time Frame: Baseline to End of Study (Estimated median duration of 12 months) ]
    Duration of Response (DoR) with SAR441000 as monotherapy and in combination with cemiplimab. DoR is time from initial response to the first documented tumor progression
  • Progression Free Survival (PFS) [ Time Frame: 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
  • Incidence of Treatment Emergent Adverse Events (TEAE) during dose expansion phase [ Time Frame: 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
  • Recommended dose of SAR441000 for expansion phase (Monotherapy) [ Time Frame: End of Dose Escalation Phase (ie., End of Cycle 1 for last patient treated at dose escalation); Cycle duration is 28 days for monotherapy ]
    SAR441000 monotherapy dose selected for expansion phase based on MTD/MAD by the Bayesian model, the overall safety, activity and PK/PDy data
  • Recommended dose of SAR441000 for expansion phase (Combination therapy) [ Time Frame: End of Dose Escalation Phase (ie., End of Cycle 1 for last patient treated at dose escalation); Cycle duration is 21 days for 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
  • For Dose Escalation: Objective Response Rate (ORR) [ Time Frame: Estimated median duration of 12 months ]
    Assessment of overall response rate using standard imaging by RECIST 1.1 and iRECIST criteria
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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  ICMJE 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
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 (Monotherapy): To determine the objective response rate of SAR441000 administered intratumorally as monotherapy in patients with advanced melanoma whose disease has progressed after prior therapy based on anti-PD-1 or anti-PD-L1.
  • 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 as monotherapy and 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 52 weeks.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Metastatic Neoplasm
Intervention  ICMJE
  • Drug: SAR441000

    Pharmaceutical form: concentrate for solution for injection

    Route of administration: intratumoral

  • Drug: Cemiplimab REGN2810

    Pharmaceutical form: solution for injection

    Route of administration: intravenous

Study Arms  ICMJE
  • Experimental: SAR441000 Dose Escalation Phase
    SAR441000 will be administered as intratumoral injection as monotherapy in patients with solid tumors over a 28-day cycle
    Intervention: Drug: SAR441000
  • Experimental: 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
    Interventions:
    • Drug: SAR441000
    • Drug: Cemiplimab REGN2810
  • Experimental: SAR441000 Expansion Cohort in Melanoma
    SAR441000 will be administered intratumorally at the determined recommended dose to patients with advanced melanoma over a 28-day cycle
    Intervention: Drug: SAR441000
  • Experimental: 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
    Interventions:
    • Drug: SAR441000
    • Drug: Cemiplimab REGN2810
  • Experimental: 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
    Interventions:
    • Drug: SAR441000
    • Drug: Cemiplimab REGN2810
  • Experimental: 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
    Interventions:
    • Drug: SAR441000
    • Drug: Cemiplimab REGN2810
  • Experimental: 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
    Interventions:
    • Drug: SAR441000
    • Drug: Cemiplimab REGN2810
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 10, 2019)
264
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2021
Estimated Primary Completion Date August 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion criteria:

  • At least 18 years of age
  • Advanced solid malignant tumor disease 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 Advanced Cutaneous Squamous Cell Cancer where no other alternative treatment option exists (expansion phases).
  • Minimum 3 lesions (patient with 2 lesions is acceptable in selected cases) at 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).
  • 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 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 and thyroiditis controlled with replacement therapies.
  • Uveal or mucosal melanoma.
  • Moderate to severe immune related adverse event to prior immune-modulating agents within 90 days prior to the first study treatment

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Trial Transparency email recommended (Toll free number for US & Canada) 800-633-1610 ext 1 then # Contact-US@sanofi.com
Listed Location Countries  ICMJE Belgium,   Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03871348
Other Study ID Numbers  ICMJE TED15297
2017-004766-94 ( EudraCT Number )
U1111-1205-1176 ( Other Identifier: UTN )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://www.clinicalstudydatarequest.com/
Responsible Party Sanofi
Study Sponsor  ICMJE Sanofi
Collaborators  ICMJE Biontech RNA Pharmaceuticals GmbH
Investigators  ICMJE
Study Director: Clinical Sciences & Operations Sanofi
PRS Account Sanofi
Verification Date January 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP