Phase 2
Completed N=109
Isatuximab in Combination With Cemiplimab in Relapsed/Refractory Multiple Myeloma (RRMM) Patients
Source: ClinicalTrials.gov NCT03194867 ↗Enrolled (actual)
109
Serious AEs
51.8%
Results posted
Jun 2024
Primary outcomePrimary: Phase 1: Number of Participants With Dose-Limiting Toxicities (DLTs) — 0 Participants
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Phase 1: Number of Participants With Dose-Limiting Toxicities (DLTs) |
— | — |
| PRIMARY Phase 1 and Phase 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) |
3; 33; 36; 33; 1; 17 | — |
| PRIMARY Phase 2: Percentage of Participants With Overall Response Rate (ORR) |
11.8; 25.0; 22.2 | — |
| SECONDARY Phase 2: Percentage of Participants With Clinical Benefit Rate (CBR) |
23.5; 36.1; 38.9 | — |
| SECONDARY Phase 2: Duration of Follow-up |
10.28; 8.84; 9.03 | — |
| SECONDARY Phase 2: Duration of Response (DOR) |
5.6; 4.7; 5.7 | — |
| SECONDARY Phase 2: Time to Response (TTR) |
1.5; 1.0; 1.0 | — |
| SECONDARY Phase 2: Progression Free Survival (PFS) |
2.89; 3.75; 3.02 | — |
| SECONDARY Phase 2: Overall Survival (OS) |
NA; NA; 12.78 | — |
| SECONDARY Phase 1 and 2: Plasma Concentration Observed at the End of IV Infusion (Ceoi) of Isatuximab Alone and in Combination With Cemiplimab |
255; 239 | — |
| SECONDARY Phase 1 and 2: Maximum Observed Concentration (Cmax) of Isatuximab Alone and in Combination With Cemiplimab |
264; 247 | — |
| SECONDARY Phase 1 and 2: Time to Reach Cmax (Tmax) of Isatuximab Alone and in Combination With Cemiplimab |
5.56; 4.85 | — |
| SECONDARY Phase 1 and 2: Last Concentration Observed Above the Lower Limit of Quantitation (Clast) of Isatuximab Alone and in Combination With Cemiplimab |
85.7; 64.1 | — |
| SECONDARY Phase 1 and 2: Time of Clast (Tlast) of Isatuximab Alone and in Combination With Cemiplimab |
155.00; 165.00 | — |
| SECONDARY Phase 1 and 2: Area Under the Concentration Versus Time Curve (AUC) From Time Zero to Tlast (AUClast) of Isatuximab Alone and in Combination With Cemiplimab |
21000; 20200 | — |
| SECONDARY Phase 1 and 2: AUC From Time 0 to Week 1 (AUC1week) of Isatuximab Alone and in Combination With Cemiplimab |
23000; 21100 | — |
| SECONDARY Phase 1 and 2: Number of Participants With Anti-Drug Antibodies (ADA) to Isatuximab |
0; 1; 0; 0; 0; 0 | — |
| SECONDARY Phase 1 and 2: Number of Participants With ADA to Cemiplimab |
1; 0; 2; 0; 0; 0 | — |
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 ( 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.
Data sourced from ClinicalTrials.gov (NCT03194867). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.