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.
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
Drug | Synonyms | Arms |
---|
Isatuximab SAR650984 | Sarclisa | Cohort A-1: mCRPC, isatuximab and REGN2810 combination |
Cemiplimab REGN2810 | | Cohort A-1: mCRPC, isatuximab and REGN2810 combination |
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
Name | Type | Description | Interventions |
---|
Phase 1: mCRPC/NSCLC | Experimental | Isatuximab dose 1 and REGN2810 predefined dose | - Isatuximab SAR650984
- Cemiplimab REGN2810
|
Cohort A-1: mCRPC, isatuximab and REGN2810 combination | Experimental | Patients 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 monotherapy | Experimental | Patients with mCRPC will be given isatuximab dose 2 | |
Phase 2 Cohort B: NSCLC | Experimental | Patients 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: mCRPC | Experimental | Isatuximab 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: NSCLC | Experimental | Isatuximab 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: | Completed |
Lead Sponsor: | Sanofi |
Trial Keywords
- Anti-CD38 monoclonal antibody
Last Updated
April 21, 2021