Isatuximab in Combination with REGN2810 (cemiplimab) in Patients with Advanced Maligancies

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

Status

Not yet recruiting

Phases

Phase 2

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2017-002846-61-GB

Enrollment

168

Registered

2017-10-05

Start date

2018-04-10

Completion date

Unknown

Last updated

2019-06-30

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

None listed

Interventions

Product Name: isatuximab Product Code: SAR650984 Pharmaceutical Form: Concentrate for solution for infusion INN or Proposed INN: isatuximab

Eligibility

Sex/Gender

All

Inclusion 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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 126 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 42

Exclusion criteria

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.

Design outcomes

Primary

Measure	Time frame
Main Objective: -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 (PDL-1)-containing therapy, or non-small cell lung cancer (NSCLC) who progressed on anti-PD-1/PDL-1-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/PDL-1 therapy naive, or NSCLC who progressed on anti-PD-1/PDL-1 therapy, or of isatuximab as single agent in patients with mCRPC ; Secondary Objective: -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. ; Primary end point(s): 1) Dose Limiting Toxicities (DLTs): 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 nonhematological 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. 2) AEs: Number of patients with AEs based on standard and systematic assessment including changes in laboratory tests and vital signs according to the National Cancer Institute - Com	—

Measure

Time frame

Main Objective: -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 (PDL-1)-containing therapy, or non-small cell lung cancer (NSCLC) who progressed on anti-PD-1/PDL-1-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/PDL-1 therapy naive, or NSCLC who progressed on anti-PD-1/PDL-1 therapy, or of isatuximab as single agent in patients with mCRPC ; Secondary Objective: -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. ; Primary end point(s): 1) Dose Limiting Toxicities (DLTs): 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 nonhematological 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. 2) AEs: Number of patients with AEs based on standard and systematic assessment including changes in laboratory tests and vital signs according to the National Cancer Institute - Com

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Secondary

Measure	Time frame
Secondary end point(s): 1) Immunogenicity: isatuximab - Levels of anti-drug antibody against isatuximab 2) Pharmacokinetic (PK) parameters: area under the curve (AUC) : AUC is area under the drug concentration versus time curve 3) Tumor burden change: The best percent-change from baseline in a sum of the diameters for all target lesions 4) Duration of response: 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. 5) Progress-free survival: 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 6) Assessment of PK parameter: Cmax - Cmax is maximum drug concentration observed 7) Immunogenicity: REGN2810 - Levels of anti-drug antibody against REGN2810 8) Disease control rate: 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. ; Timepoint(s) of evaluation of this end point: 1) and 7) 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) 2) and 6) Up to 3 weeks after first study treatment administration 3), 4) , 5) and 8) Up to 12 months from last patient in	—

Measure

Time frame

Secondary end point(s): 1) Immunogenicity: isatuximab - Levels of anti-drug antibody against isatuximab 2) Pharmacokinetic (PK) parameters: area under the curve (AUC) : AUC is area under the drug concentration versus time curve 3) Tumor burden change: The best percent-change from baseline in a sum of the diameters for all target lesions 4) Duration of response: 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. 5) Progress-free survival: 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 6) Assessment of PK parameter: Cmax - Cmax is maximum drug concentration observed 7) Immunogenicity: REGN2810 - Levels of anti-drug antibody against REGN2810 8) Disease control rate: 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. ; Timepoint(s) of evaluation of this end point: 1) and 7) 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) 2) and 6) Up to 3 weeks after first study treatment administration 3), 4) , 5) and 8) Up to 12 months from last patient in

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Countries

France, Italy, Taiwan, United Kingdom, United States

Contacts

Public ContactMedical Information

Sanofi-aventis recherche & développement

uk-medicalinformation@sanofi.com+441483505515

Outcome results