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

NCT03194867 | Completed Phase 1 Results DMC FDA Drug

• 3 other identifiers: TCD149062017-001431-39U1111-1189-4706
• Study Type: interventional
• Target: 109
• Locations: 10 countries
• Sites: 30

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.

Conditions

Plasma Cell Myeloma

Keywords

Anti-CD38 monoclonal antibody

Outcome Measures

Primary Outcomes (3)

• Phase 1: Number of Participants With Dose-Limiting Toxicities (DLTs)

  Potential DLTs were defined as the occurrence of any of the following adverse reactions at first treatment cycle, unless due to disease progression or obviously unrelated cause: Hematological DLTs: Grade(G) 4 neutropenia (N) for more than 7 consecutive days, G3 to G4 N complicated by fever (temperature greater than or equal to \[\>=\] 38.5 degree Celsius on more than 1 occasion) or microbiologically/radiographically documented infection, G3 to G4 thrombocytopenia associated with clinically significant bleeding requiring clinical intervention or Non-hematological DLTs: G4 non-hematologic AE, G\>=2 uveitis, G3 non-hematological AE lasting greater than (\>)3 days despite optimal care support, delay in initiation of Cycle 2 \>14 days due to treatment related laboratory abnormalities/AE. Any other AE that the investigator/study committee deemed to be dose-limiting, regardless of grade, was also considered as DLT.

  Cycle 1 Day 1 to Day 28

• Phase 1 and Phase 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)

  An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant administered with a pharmaceutical product and which did not necessarily have a causal relationship with study treatment. SAEs were any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. TEAEs were defined as an AE which occurred after the first dose of study treatment administration up to 30 days after the last dose of study treatment administration. The DLT observation period was 1 cycle (28 days). However, all AEs during treatment, unless due to disease progression or an obviously unrelated cause, were taken into consideration by the Study Committee for the determination of the maximum tolerated dose and recommended Phase 2 dose.

  TEAEs were collected from the first dose up to 30 days after the last dose of study treatment, approximately 50 months

• Phase 2: Percentage of Participants With Overall Response Rate (ORR)

  ORR by Investigator using international myeloma working group (IMWG) response criteria:percentage of participants with complete response (CR) (including stringent CR \[sCR\]very good partial response \[VGPR\] and partial response \[PR\]).CR:negative immunofixation on serum and urine,disappearance of any soft tissue plasmacytomas,less than (\<)5% plasma cells in bone marrow (BM) aspirates and normal free light chain(FLC)ratio (0.26-1.65).sCR:CR plus no clonal cells in BM biopsy.VGPR:serum and urine M-protein detectable by immunofixation,not electrophoresis;\>=90% reduction in serum M-protein plus urine M-protein level\<100mg/24hour(h);FLC only:\>=90% decrease in difference between involved and uninvolved FLC levels.PR:\>=50% reduction of serum M-protein and reduction in 24h urine M-protein by \>=90% or \<200mg/24h.In addition to above, if present at baseline,\>=50% reduction in size (sum of products of maximal perpendicular diameters of measured lesions \[SPD\]) of soft tissue plasmacytomas required.

  From Cycle 1 Day 1 up to primary analysis completion date of 9 Oct 2019 i.e., up to approximately 17 months

Secondary Outcomes (15)

• Phase 2: Percentage of Participants With Clinical Benefit Rate (CBR)

  From Cycle 1 Day 1 up to primary analysis completion date of 9 Oct 2019 i.e., up to approximately 17 months

• Phase 2: Duration of Follow-up

  From the date of randomization up to primary analysis completion date of 9 Oct 2019 i.e., up to approximately 17 months

• Phase 2: Duration of Response (DOR)

  From Cycle 1 Day 1 up to primary analysis completion date of 9 Oct 2019 i.e., up to approximately 17 months

• Phase 2: Time to Response (TTR)

  From Cycle 1 Day 1 up to primary analysis completion date of 9 Oct 2019 i.e., up to approximately 17 months

• Phase 2: Progression Free Survival (PFS)

  From Cycle 1 Day 1 up to primary analysis completion date of 9 Oct 2019 i.e., up to approximately 17 months

Study Arms (3)

Isatuximab/cemiplimab (Regimen 1)

EXPERIMENTAL

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; Drug: Cemiplimab REGN2810

Isatuximab/cemiplimab (Regimen 2)

EXPERIMENTAL

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; Drug: Cemiplimab REGN2810

Isatuximab

ACTIVE COMPARATOR

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

Drug: Isatuximab SAR650984

Interventions

Isatuximab SAR650984 DRUG

Pharmaceutical form: solution for infusion Route of administration: intravenous

Also known as: Sarclisa

Isatuximab; Isatuximab/cemiplimab (Regimen 1); Isatuximab/cemiplimab (Regimen 2)

Cemiplimab REGN2810 DRUG

Pharmaceutical form: solution for infusion Route of administration: intravenous

Isatuximab/cemiplimab (Regimen 1); Isatuximab/cemiplimab (Regimen 2)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (30)

University of Colorado-Site Number:8400001

Denver, Colorado, 80262, United States

Location

University of Kansas Medical Center-Site Number:8400003

Kansas City, Kansas, 66160-7321, United States

Location

Memorial Sloan-Kettering Cancer Center-Site Number:8400002

New York, New York, 10021, United States

Location

Fox Chase Cancer Center-Site Number:8400004

Philadelphia, Pennsylvania, 19111, United States

Location

Investigational Site Number :0360003

Wollongong, New South Wales, 2500, Australia

Location

Investigational Site Number :0360002

Richmond, Victoria, 3121, Australia

Location

Investigational Site Number :0360001

West Perth, Western Australia, 6005, Australia

Location

Investigational Site Number :0760003

Goiânia, Goiás, 74605-020, Brazil

Location

Investigational Site Number :0760001

Porto Alegre, Rio Grande do Sul, 90110-270, Brazil

Location

Investigational Site Number :0760004

São Paulo, São Paulo, 01236030, Brazil

Location

Investigational Site Number :1240001

Montreal, Quebec, H1T 2M4, Canada

Location

Investigational Site Number :1240005

Montreal, Quebec, H4J 1C5, Canada

Location

Investigational Site Number :1240003

Sherbrooke, Quebec, J1H 5N4, Canada

Location

Investigational Site Number :2030002

Brno, 62500, Czechia

Location

Investigational Site Number :2030003

Ostrava - Poruba, 70852, Czechia

Location

Investigational Site Number :2030001

Prague, 12808, Czechia

Location

Investigational Site Number :2500004

Lille, 59037, France

Location

Investigational Site Number :2500002

Nantes, 44093, France

Location

Investigational Site Number :2500003

Pierre-Bénite, 69495, France

Location

Investigational Site Number :2500001

Villejuif, 94800, France

Location

Investigational Site Number :3000001

Athens, 11528, Greece

Location

Investigational Site Number :3480002

Budapest, 1083, Hungary

Location

Investigational Site Number :3800005

Rozzano, Milano, 20089, Italy

Location

Investigational Site Number :3800003

Brescia, 25123, Italy

Location

Investigational Site Number :3800001

Torino, 10126, Italy

Location

Investigational Site Number :7240003

Barcelona, Barcelona [Barcelona], 08035, Spain

Location

Investigational Site Number :7240004

Badalona, Catalunya [Cataluña], 08916, Spain

Location

Investigational Site Number :7240002

Barcelona, Catalunya [Cataluña], 08036, Spain

Location

Investigational Site Number :7240005

Valencia, Valenciana, Comunidad, 46017, Spain

Location

Investigational Site Number :7240006

Madrid, 28041, Spain

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

isatuximab; cemiplimab

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi aventis recherche & développement

Contact-US@sanofi.com

800-633-1610

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 19, 2017
• First Posted: June 21, 2017
• Study Start: February 21, 2018
• Primary Completion: April 5, 2023
• Study Completion: April 5, 2023
• Last Updated: June 14, 2024
• Results First Posted: June 14, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will share

Locations

IT (3); AU (3); CZ (3); GR (1); HU (1); ES (5); CA (3); FR (4); BR (3); US (4)