Isatuximab in Combination With Cemiplimab in Relapsed/Refractory Multiple Myeloma (RRMM) Patients

• ClinicalTrials.gov Identifier: NCT03194867
• Recruitment Status: Completed
• First Posted: June 21, 2017
• Last Update Posted: April 19, 2023
• Sponsor: Sanofi
• Information provided by (Responsible Party): Sanofi

Tracking Information

• First Submitted Date: June 19, 2017
• First Posted Date: June 21, 2017
• Last Update Posted Date: April 19, 2023
• Actual Study Start Date: January 25, 2018
• Actual Primary Completion Date: April 5, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 29, 2018)

• Dose Limiting Toxicities (DLTs) [ Time Frame: Up to 4 weeks ]
  DLTs are following 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/AE
• Adverse events (AEs) and changes in laboratory tests and vital signs [ Time Frame: Up to 90 days following the last administration of study treatment for ongoing related AE, ongoing serious AE and new related AE until resolution or stabilization ]
  Number of patients with AEs and changes in laboratory tests and vital signs according to the National Cancer Institute - Common Toxicity Criteria (NCI-CTC) version 4.03 Grade scaling
• Overall Response Rate (ORR) [ Time Frame: Up to 6 months from last patient in (LPI) for primary efficacy analysis, and up to 12 months from LPI for the final analysis ]
  ORR is defined as the proportion of patients with complete response (CR) (including sCR [stringent complete response]), very good partial response (VGPR) and partial response (PR)

Original Primary Outcome Measures (submitted: June 19, 2017)

• Dose Limiting Toxicities (DLTs) [ Time Frame: Up to 4 weeks ]
  DLTs are following 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/AE
• Adverse events (AEs) and changes in laboratory tests and vital signs [ Time Frame: Up to 30 days following the last administration of study treatment for ongoing related AE, ongoing serious AE and new related AE until resolution or stabilization ]
  Number of patients with AEs and changes in laboratory tests and vital signs according to the National Cancer Institute - Common Toxicity Criteria (NCI-CTC) version 4.03 Grade scaling
• Overall Response Rate (ORR) [ Time Frame: Up to 6 months from last patient in (LPI) for primary efficacy analysis, and up to 12 months from LPI for the final analysis ]
  ORR is defined as the proportion of patients with complete response (CR) (including sCR [stringent complete response]), very good partial response (VGPR) and partial response (PR)

Current Secondary Outcome Measures (submitted: January 29, 2018)

• Clinical Benefit Rate (CBR) [ Time Frame: Up to 6 months from LPI for primary efficacy analysis, and up to 12 months from LPI for the final analysis ]
  CBR is defined as the proportion of patients with CR (including sCR), VGPR, PR and minimal response (MR)
• Duration of Response (DOR) [ Time Frame: Up to 6 months from LPI for primary efficacy analysis, and up to 12 months from LPI for the final analysis ]
  DOR is defined as the time from the date of the first response (≥PR) that is subsequently confirmed to the date of first confirmed disease progression or death, whichever happens first
• Time to Response (TTR) [ Time Frame: Up to 6 months from LPI for primary efficacy analysis, and up to 12 months from LPI for the final analysis ]
  TTR is defined as time from first study treatment administration to first response (≥PR) that is subsequently confirmed
• Progression Free Survival (PFS) [ Time Frame: Up to 6 months from LPI for primary efficacy analysis, and up to 12 months from LPI for the final analysis ]
  PFS is 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
• Overall Survival (OS) [ Time Frame: Up to 12 months from LPI for the final analysis ]
  OS defined as the time from the first study treatment administration to death from any cause
• Assessment of PK parameter: partial AUC [ Time Frame: Up to 4 weeks ]
  AUC is area under the drug concentration versus time curve
• Assessment of PK parameter: Cmax [ Time Frame: Up to 4 weeks ]
  Cmax is maximum drug concentration observed
• Antibodies to isatuximab [ Time Frame: Up to 12 months from LPI for the final analysis ]
  Levels of anti isatuximab antibodies in plasma samples will be determined
• Antibodies to cemiplimab [ Time Frame: Up to 12 months from LPI for the final analysis ]
  Levels of anti cemiplimab antibodies in serum samples will be determined

Original Secondary Outcome Measures (submitted: June 19, 2017)

• Clinical Benefit Rate (CBR) [ Time Frame: Up to 6 months from LPI for primary efficacy analysis, and up to 12 months from LPI for the final analysis ]
  CBR is defined as the proportion of patients with CR (including sCR), VGPR, PR and minimal response (MR)
• Duration of Response (DOR) [ Time Frame: Up to 6 months from LPI for primary efficacy analysis, and up to 12 months from LPI for the final analysis ]
  DOR is defined as the time from the date of the first response (≥PR) that is subsequently confirmed to the date of first confirmed disease progression or death, whichever happens first
• Time to Response (TTR) [ Time Frame: Up to 6 months from LPI for primary efficacy analysis, and up to 12 months from LPI for the final analysis ]
  TTR is defined as time from first study treatment administration to first response (≥PR) that is subsequently confirmed
• Progression Free Survival (PFS) [ Time Frame: Up to 6 months from LPI for primary efficacy analysis, and up to 12 months from LPI for the final analysis ]
  PFS is 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
• Overall Survival (OS) [ Time Frame: Up to 12 months from LPI for the final analysis ]
  OS defined as the time from the first study treatment administration to death from any cause
• Assessment of PK parameter: partial AUC [ Time Frame: Up to 4 weeks ]
  AUC is area under the drug concentration versus time curve
• Assessment of PK parameter: Cmax [ Time Frame: Up to 4 weeks ]
  Cmax is maximum drug concentration observed
• Antibodies to isatuximab [ Time Frame: Up to 12 months from LPI for the final analysis ]
  Levels of anti isatuximab antibodies in plasma samples will be determined
• Antibodies to REGN2810 [ Time Frame: Up to 12 months from LPI for the final analysis ]
  Levels of anti REGN2810 antibodies in serum samples will be determined

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Isatuximab in Combination With Cemiplimab in Relapsed/Refractory Multiple Myeloma (RRMM) Patients
• Official Title: A Phase 1/2 Study to Evaluate Safety, Pharmacokinetics and Efficacy of Isatuximab in Combination With Cemiplimab in Patients With Relapsed/Refractory Multiple Myeloma

Brief Summary

Primary Objectives:

• To evaluate the safety and tolerability of the combination of isatuximab (also known as SAR650984) and cemiplimab (also known as REGN2810) in patients with relapse/refractory multiple myeloma.
• To compare the overall response of the combination of isatuximab and cemiplimab versus isatuximab alone in patients with RRMM based on International Myeloma Working Group (IMWG) criteria.

Secondary Objectives:

• To evaluate the efficacy as assessed by clinical benefit rate (CBR), duration of response (DOR), time to response (TTR), progression free survival (PFS), and overall survival (OS).
• To assess the pharmacokinetics (PK) of isatuximab and cemiplimab when given in combination.
• To assess the immunogenicity of isatuximab and cemiplimab when given in combination.

• Detailed Description: The duration of the study for a patient will include a period for screening of up to 21 days and 3-month post treatment follow up. The cycle duration is 28 days. Patients will continue treatment until disease progression, unacceptable adverse events, consent withdrawal, or any other reason.
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Plasma Cell Myeloma

Intervention

• Drug: Isatuximab SAR650984

  Pharmaceutical form: solution for infusion

  Route of administration: intravenous

  Other Name: Sarclisa
• Drug: Cemiplimab REGN2810

  Pharmaceutical form: solution for infusion

  Route of administration: intravenous

Study Arms

• Experimental: Isatuximab/cemiplimab (Regimen 1)

  Isatuximab on Days 1, 8, 15, and 22, then Days 1 and 15 in 28-day cycles up to disease progression.

  Cemiplimab on Days 1 and 15 in 28-day cycle up to disease progression.

  Interventions:

  • Drug: Isatuximab SAR650984
  • Drug: Cemiplimab REGN2810
• Experimental: Isatuximab/cemiplimab (Regimen 2)

  Isatuximab on Days 1, 8, 15, and 22, then Days 1 and 15 in 28-day cycles up to disease progression.

  Cemiplimab on Day 1 in 28-day cycle up to disease progression.

  Interventions:

  • Drug: Isatuximab SAR650984
  • Drug: Cemiplimab REGN2810
• Active Comparator: Isatuximab
  Isatuximab on Days 1, 8, 15 and 22, then Day 1 and 15 in 28-day cycles up to disease progression.
  Intervention: Drug: Isatuximab SAR650984

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 12, 2019): 109
• Original Estimated Enrollment (submitted: June 19, 2017): 54
• Actual Study Completion Date: April 5, 2023
• Actual Primary Completion Date: April 5, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion criteria:

• Patients must have a known diagnosis of multiple myeloma with evidence of measurable disease, as defined below:

  • Serum M-protein ≥1 g/dL (≥0.5 g/dL in case of immunoglobulin A [IgA] disease), AND/OR
  • Urine M-protein ≥200 mg/24 hours, OR
  • In the absence of measurable M-protein, serum immunoglobulin free light chain ≥10 mg/dL, and abnormal serum immunoglobulin kappa lambda free light chain ratio (<0.26 or >1.65).
• Patients must have received prior treatment with an immunomodulatory drug (IMiD) (for ≥2 cycles or ≥2 months of treatment) and a proteasome inhibitor (PI) (for ≥2 cycles or ≥2 months of treatment).
• Patients must have received at least 3 prior lines of therapy (Note: Induction therapy and stem cell transplant ± maintenance will be considered as one line).
• Patient must have achieved MR or better with any anti-myeloma therapy (ie, primary refractory disease is not eligible).

Exclusion criteria:

• Prior exposure to isatuximab or participated clinical studies with isatuximab.
• Prior exposure to any agent (approved or investigational) that blocks the programmed cell death-1 (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 30 days of planned treatment start. Seasonal flu vaccines that do not contain live virus are permitted.
• Has allogenic haemopoietic stem cell (HSC) transplant.
• Prior treatment with idelalisib (a PI3K inhibitor).
• Eastern Cooperative Oncology Group (ECOG) 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Brazil, Canada, Czechia, France, Greece, Hungary, Italy, Spain, United States

Administrative Information

• NCT Number: NCT03194867
• Other Study ID Numbers: TCD14906; 2017-001431-39 ( EudraCT Number ); U1111-1189-4706 ( Other Identifier: UTN )
• Has Data Monitoring Committee: Yes

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

• 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://vivli.org

• Current Responsible Party: Sanofi
• Original Responsible Party: Same as current
• Current Study Sponsor: Sanofi
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Sciences & Operations; Sanofi

• PRS Account: Sanofi
• Verification Date: April 18, 2023