Background. RRMM (relapsed or refractory multiple myeloma) remains a major change in the Myeloma disease development as it implies a shortening in overall survival with subsequent relapses; and consequently, RRMM is in constant need of novel treatment options to prolong survival. The triplet-based association of antiCD38 immunotherapy (antiCD38 IT) with either second generation of Imids (Pomalidomide) and dexamethasone or second-generation proteasome inhibitors (PI) such as Carfilzomib and dexamethasone has become the new standard of care in early relapse MM. However, quadruplet-based regimens (antiCD38 immunotherapy +Imids +PI +dexamethasone) have transformed the treatment landscape in the upfront setting, improving MRD (minimal residual disease) and survivals. We hypothesized that a quadruplet-based regimens (antiCD38 immunotherapy +Imids +PI +dexamethasone) would further improved MRD and survival in early RRMM. Here, we describe a phase II multicentric, open-label study, of isatuximab (antiCD38 IT), pomalidomide and dexamethasone plus carfilzomib (IsKPd/ IFM2018-03, NCT04287855) for patients with early RRMM. Study design and Methods. Approximately 90 patients will receive the association isatuximab, pomalidomide and dexamethasone with carfilzomib (IsKPd). Eligible patients are adults aged ≥18 years old with RRMM previously treated with 1 or 2 lines of therapy, including lenalidomide, prior to the study entry. Patients were excluded if they were refractory to any anti-CD38 monoclonal antibody or to carfilzomib, or if they were previously exposed to pomalidomide. Isatuximab will be given by IV route at 10 mg/kg on days 1, 8, 15, and 22 of cycle 1, on days 1 and 15 from cycle 2 to 12 and on day 1 only from cycle 13, 28-day cycles. Carfilzomib will be given by IV route at 20/27 mg/m² on days 1-2, 8-9, 15-16 during cycle 1, at 56mg/m² on days 1, 8, 15 from cycle 2 to 13 and at 56mg/m² on days 1 and 15 after cycle 13. Pomalidomide will be administered by oral route at 3 mg daily on days 1 to 21 in cycle 1 and at 4 mg daily from cycle 12. Dexamethasone will be given by oral route at 40/20 mg daily on days 1, 8, 15 and 22. The primary objective is to evaluate the MRD rate at 10-5 in patients with RRMM treated with IsKPd. Patients will pursue Isa-KPd until progression or unacceptable toxicity. Key secondary objectives include the survival analysis (OS, PFS, EFS, TTNT), response rates and duration of response and evaluation of the safety profile. The IFM2018-03 study is currently enrolling patients in several centers in France. The study is expected to complete recruitment in 2022 and read primary end point in 2023. Clinical trial information: NCT04287855.