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

A Phase 1/2 Study to Evaluate Safety, Pharmacokinetics and Efficacy of Isatuximab in Combination With Cemiplimab in Patients With Relapsed/Refractory Multiple Myeloma

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.

Study Overview

• Status: Completed
• Conditions: Plasma Cell Myeloma
• Intervention / Treatment: Drug: Isatuximab SAR650984; Drug: Cemiplimab REGN2810

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
• Enrollment (Actual): 109
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Wollongong, New South Wales, Australia, 2500
      • Investigational Site Number :0360003
  • Victoria
    • Richmond, Victoria, Australia, 3121
      • Investigational Site Number :0360002
  • Western Australia
    • West Perth, Western Australia, Australia, 6005
      • Investigational Site Number :0360001
• Brazil
  • Goiás
    • Goiania, Goiás, Brazil, 74605-020
      • Investigational Site Number :0760003
  • Rio Grande Do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90110-270
      • Investigational Site Number :0760001
  • São Paulo
    • Sao Paulo, São Paulo, Brazil, 01236030
      • Investigational Site Number :0760004
• Canada
  • Quebec
    • Montreal, Quebec, Canada, H1T 2M4
      • Investigational Site Number :1240001
    • Montreal, Quebec, Canada, H4J 1C5
      • Investigational Site Number :1240005
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • Investigational Site Number :1240003
• Czechia
  • Brno, Czechia, 62500
    • Investigational Site Number :2030002
  • Ostrava - Poruba, Czechia, 70852
    • Investigational Site Number :2030003
  • Praha 2, Czechia, 12808
    • Investigational Site Number :2030001
• France
  • Lille, France, 59037
    • Investigational Site Number :2500004
  • Nantes, France, 44093
    • Investigational Site Number :2500002
  • Pierre Benite, France, 69495
    • Investigational Site Number :2500003
  • Villejuif, France, 94800
    • Investigational Site Number :2500001
• Greece
  • Athens, Greece, 11528
    • Investigational Site Number :3000001
• Hungary
  • Budapest, Hungary, 1083
    • Investigational Site Number :3480002
• Italy
  • Brescia, Italy, 25123
    • Investigational Site Number :3800003
  • Torino, Italy, 10126
    • Investigational Site Number :3800001
  • Milano
    • Rozzano, Milano, Italy, 20089
      • Investigational Site Number :3800005
• Spain
  • Madrid, Spain, 28041
    • Investigational Site Number :7240006
  • Barcelona [Barcelona]
    • Barcelona, Barcelona [Barcelona], Spain, 08035
      • Investigational Site Number :7240003
  • Catalunya [Cataluña]
    • Badalona, Catalunya [Cataluña], Spain, 08916
      • Investigational Site Number :7240004
    • Barcelona, Catalunya [Cataluña], Spain, 08036
      • Investigational Site Number :7240002
  • Valenciana, Comunidad
    • Valencia, Valenciana, Comunidad, Spain, 46017
      • Investigational Site Number :7240005
• United States
  • Colorado
    • Denver, Colorado, United States, 80262
      • University of Colorado-Site Number:8400001
  • Kansas
    • Kansas City, Kansas, United States, 66160-7321
      • University of Kansas Medical Center-Site Number:8400003
  • New York
    • New York, New York, United States, 10021
      • Memorial Sloan-Kettering Cancer Center-Site Number:8400002
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center-Site Number:8400004

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	Drug: Isatuximab SAR650984; Pharmaceutical form: solution for infusion Route of administration: intravenous; Other Names: Sarclisa; Drug: Cemiplimab REGN2810; Pharmaceutical form: solution for infusion Route of administration: intravenous
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.	Drug: Isatuximab SAR650984; Pharmaceutical form: solution for infusion Route of administration: intravenous; Other Names: Sarclisa; Drug: Cemiplimab REGN2810; Pharmaceutical form: solution for infusion Route of administration: intravenous
Active Comparator: Isatuximab; Isatuximab on Days 1, 8, 15 and 22, then Day 1 and 15 in 28-day cycles up to disease progression.	Drug: Isatuximab SAR650984; Pharmaceutical form: solution for infusion Route of administration: intravenous; Other Names: Sarclisa

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose Limiting Toxicities (DLTs)	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	Up to 4 weeks
Adverse events (AEs) and changes in laboratory tests and vital signs	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	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
Overall Response Rate (ORR)	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)	Up to 6 months from last patient in (LPI) for primary efficacy analysis, and up to 12 months from LPI for the final analysis

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Sanofi

Study record dates

Study Major Dates

• Study Start (Actual): January 25, 2018
• Primary Completion (Actual): April 5, 2023
• Study Completion (Actual): April 5, 2023

Study Registration Dates

• First Submitted: June 19, 2017
• First Submitted That Met QC Criteria: June 19, 2017
• First Posted (Actual): June 21, 2017

Study Record Updates

• Last Update Posted (Actual): April 19, 2023
• Last Update Submitted That Met QC Criteria: April 18, 2023
• Last Verified: April 18, 2023

More Information

Terms related to this study

• Keywords: Anti-CD38 monoclonal antibody
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Antineoplastic Agents; Antineoplastic Agents, Immunological; Cemiplimab
• Other Study ID Numbers: TCD14906; 2017-001431-39 (EudraCT Number); U1111-1189-4706 (Other Identifier: UTN)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No