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

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ClinicalTrials.gov Identifier: NCT03194867
Recruitment Status : Recruiting
First Posted : June 21, 2017
Last Update Posted : November 9, 2018
Sponsor:
Information provided by (Responsible Party):
Sanofi

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.

Condition or disease Intervention/treatment Phase
Plasma Cell Myeloma Drug: Isatuximab SAR650984 Drug: Cemiplimab REGN2810 Phase 1 Phase 2

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  (Clinical Trial)
Estimated Enrollment : 105 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : February 21, 2018
Estimated Primary Completion Date : August 2022
Estimated Study Completion Date : August 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

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


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


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





Primary Outcome Measures :
  1. 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

  2. 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

  3. 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)


Secondary Outcome Measures :
  1. 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)

  2. 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

  3. 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

  4. 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

  5. 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

  6. Assessment of PK parameter: partial AUC [ Time Frame: Up to 4 weeks ]
    AUC is area under the drug concentration versus time curve

  7. Assessment of PK parameter: Cmax [ Time Frame: Up to 4 weeks ]
    Cmax is maximum drug concentration observed

  8. 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

  9. 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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03194867


Contacts
Contact: Trial Transparency email recommended (Toll free number for US & Canada) 800-633-1610 ext 1 then # Contact-Us@sanofi.com

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Sponsors and Collaborators
Sanofi
Investigators
Study Director: Clinical Sciences & Operations Sanofi

Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT03194867     History of Changes
Other Study ID Numbers: TCD14906
2017-001431-39 ( EudraCT Number )
U1111-1189-4706 ( Other Identifier: UTN )
First Posted: June 21, 2017    Key Record Dates
Last Update Posted: November 9, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Individual participant data (IPD) and supporting clinical documents are available for request at clinicalstudydatarequest.com. While making information available Sanofi continues to protect the privacy of the participants in clinical trials and to remove commercially confidential information (CCI). Details on Data Sharing criteria and process for requesting access can be found at this web address: clinicalstudydatarequest.com

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases