Clinical Trials /

Isatuximab in Combination With REGN2810 (Cemiplimab) in Patients With Advanced Malignancies

NCT03367819

Description:

Primary Objectives: - To characterize the safety and tolerability of isatuximab in combination with REGN2810 in patients with metastatic, castration-resistant prostate cancer (mCRPC) who are naïve to anti-programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1)-containing therapy, or non-small cell lung cancer (NSCLC) who progressed on anti-PD-1/PD-L1-containing therapy, and to confirm the recommended Phase 2 dose (RP2D). - To assess the response rate of isatuximab in combination with REGN2810 in patients with either mCRPC who are anti-PD-1/PD-L1 therapy naive, or NSCLC who progressed on anti-PD-1/PD-L1 therapy, or of isatuximab as single agent in patients with mCRPC. Secondary Objectives: - To evaluate the safety of the combination of isatuximab with REGN2810 or isatuximab monotherapy. - To evaluate the immunogenicity of isatuximab and REGN2810. - To characterize the pharmacokinetic (PK) profile of isatuximab single agent or in combination with REGN2810, and to characterize the PK of REGN2810 in combination with isatuximab. - To assess overall efficacy of isatuximab in combination with REGN2810 or as a single agent.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
  • Prostate Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Isatuximab in Combination With REGN2810 (Cemiplimab) in Patients With Advanced Malignancies
  • Official Title: A Phase 1/2 Open-label, Multi-center, Safety, Preliminary Efficacy and Pharmacokinetic (PK) Study of Isatuximab (SAR650984) in Combination With REGN2810, or Isatuximab Alone, in Patients With Advanced Malignancies

Clinical Trial IDs

  • ORG STUDY ID: ACT15319
  • SECONDARY ID: 2017-002846-61
  • SECONDARY ID: U1111-1197-7792
  • NCT ID: NCT03367819

Conditions

  • Prostate Cancer
  • Non-small Cell Lung Cancer

Interventions

DrugSynonymsArms
Isatuximab SAR650984Phase 2 Cohort B: NSCLC
Cemiplimab REGN2810Phase 2 Cohort B: NSCLC

Purpose

Primary Objectives: - To characterize the safety and tolerability of isatuximab in combination with REGN2810 in patients with metastatic, castration-resistant prostate cancer (mCRPC) who are naïve to anti-programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1)-containing therapy, or non-small cell lung cancer (NSCLC) who progressed on anti-PD-1/PD-L1-containing therapy, and to confirm the recommended Phase 2 dose (RP2D). - To assess the response rate of isatuximab in combination with REGN2810 in patients with either mCRPC who are anti-PD-1/PD-L1 therapy naive, or NSCLC who progressed on anti-PD-1/PD-L1 therapy, or of isatuximab as single agent in patients with mCRPC. Secondary Objectives: - To evaluate the safety of the combination of isatuximab with REGN2810 or isatuximab monotherapy. - To evaluate the immunogenicity of isatuximab and REGN2810. - To characterize the pharmacokinetic (PK) profile of isatuximab single agent or in combination with REGN2810, and to characterize the PK of REGN2810 in combination with isatuximab. - To assess overall efficacy of isatuximab in combination with REGN2810 or as a single agent.

Detailed Description

      The total study duration per patient is up to 28 months including an up to 28 days screening
      period, an up to 24 months treatment period, and a 3 months safety follow up period.
    

Trial Arms

NameTypeDescriptionInterventions
Phase 1: mCRPC/NSCLCExperimentalIsatuximab dose 1 and REGN2810 predefined dose
  • Isatuximab SAR650984
  • Cemiplimab REGN2810
Cohort A-1: mCRPC, isatuximab and REGN2810 combinationExperimentalPatients with mCRPC will be given isatuximab dose determined in Phase 1 arm of study and REGN2810 predefined dose
  • Isatuximab SAR650984
  • Cemiplimab REGN2810
Cohort A-2: mCRPC, isatuximab monotherapyExperimentalPatients with mCRPC will be given isatuximab dose 2
  • Isatuximab SAR650984
Phase 2 Cohort B: NSCLCExperimentalPatients with NSCLC will be given isatuximab dose determined in Phase 1 arm of study and REGN2810 predefined dose
  • Isatuximab SAR650984
  • Cemiplimab REGN2810
Phase 2 Cohort C: mCRPCExperimentalIsatuximab dose 3 will be given in combination with REGN2810 predefined dose or isatuximab dose 3 will be given as monotherapy in patients with mCRPC
  • Isatuximab SAR650984
  • Cemiplimab REGN2810
Phase 2 Cohort D: NSCLCExperimentalIsatuximab dose 3 will be given in combination with REGN2810 predefined dose
  • Isatuximab SAR650984
  • Cemiplimab REGN2810

Eligibility Criteria

        Inclusion criteria:

          -  Patients must have a known diagnosis of either metastatic castration-resistant
             prostate cancer (mCRPC) or non-small cell lung cancer (NSCLC) with evidence of
             measurable disease.

          -  Failure of, inability to, or refusal to receive standard of care.

          -  ≥18 years of age.

        Exclusion criteria:

          -  Prior exposure to isatuximab or participation in clinical studies with isatuximab.

          -  For patients with mCRPC, prior exposure to any agent (approved or investigational)
             that blocks the PD-1/PD-L1 pathway.

          -  Evidence of other immune related disease /conditions.

          -  History of non-infectious pneumonitis requiring steroids or current pneumonitis;
             history of the thoracic radiation.

          -  Has received a live-virus vaccination within 28 days of planned treatment start.
             Seasonal flu vaccines that do not contain live virus are permitted.

          -  Prior solid organ or hematologic transplant.

          -  Eastern Cooperative Oncology Group performance status (PS) ≥2.

          -  Poor bone marrow reserve.

          -  Poor organ function.

        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:Dose Limiting Toxicities (DLTs)
Time Frame:Up to 3 weeks after first study treatment administration
Safety Issue:
Description:DLTs are following adverse events (AEs) in Cycle 1 unless due to disease progression or an obviously unrelated cause: Grade (G) 4 neutropenia >7 days; G 3 to 4 neutropenia with fever or documented infection; G 3 to 4 thrombocytopenia with bleeding requiring intervention; G 4 non-hematological AE; G ≥2 uveitis; G 3 non-hematological AE >3 days despite supportive care (with defined exceptions); Delay in initiation of the 2nd cycle >14 days for related laboratory abnormalities/AEs

Secondary Outcome Measures

Measure:Immunogenicity: isatuximab
Time Frame:Up to 90 days following the last administration of study treatment or until the sample is negative (Up to approximately 27 months after first study treatment administration)
Safety Issue:
Description:Levels of anti-drug antibody against isatuximab
Measure:Pharmacokinetic (PK) parameters: area under the curve (AUC)
Time Frame:Up to 3 weeks after first study treatment administration
Safety Issue:
Description:AUC is area under the drug concentration versus time curve
Measure:Tumor burden change
Time Frame:Up to 12 months from last patient in
Safety Issue:
Description:The best percent-change from baseline in a sum of the diameters for all target lesions
Measure:Duration of response
Time Frame:Up to 12 months from last patient in
Safety Issue:
Description:Defined as the time from the date of the first response that is subsequently confirmed to the date of first confirmed disease progression or death, whichever occurs first
Measure:Progression-free survival
Time Frame:Up to 12 months from last patient in
Safety Issue:
Description:Defined as time from the first study treatment administration to the date of first documentation of progressive disease that is subsequently confirmed or the date of death from any cause
Measure:Assessment of PK parameter: Cmax
Time Frame:Up to 3 weeks after first study treatment administration
Safety Issue:
Description:Cmax is maximum drug concentration observed
Measure:Immunogenicity: REGN2810
Time Frame:Up to 90 days following the last administration of study treatment or until the sample is negative (Up to approximately 27 months after first study treatment administration)
Safety Issue:
Description:Levels of anti-drug antibody against REGN2810
Measure:Disease control rate
Time Frame:Up to 12 months from last patient in
Safety Issue:
Description:Defined as the proportion of patients with confirmed complete response or partial response or stable disease, as assessed by Investigator relative to the total number of patients in the analysis population

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Sanofi

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