Phase III (IKEMA) study design: Isatuximab plus carfilzomib and dexamethasone (Kd) vs Kd in patients with relapsed/refractory multiple myeloma (RRMM).

TPS8060 Background: Multiple myeloma (MM) remains an incurable disease requiring multiple lines of therapy, in which carfilzomib-based treatments are a standard of care. Isatuximab (ISA), an anti-CD38-targeted monoclonal antibody with antitumor and immunomodulatory activities in preclinical models of MM, has shown clinical activity as monotherapy and in combination with current standard of care in patients (pts) with RRMM. Methods: This Phase III, prospective, randomized, open-label study (NCT03275285; IKEMA) will evaluate the clinical benefit of ISA in combination with Kd versus Kd alone in pts with RRMM, who have received 1–3 prior lines of therapy. Pts who have received prior carfilzomib therapy, have primary refractory disease, or have free light chain measurable disease only will be excluded. Approximately 300 pts will be randomized according to 2 stratification factors (prior lines of therapy: 1 vs > 1; revised international staging system at baseline: I or II vs III vs unknown) in a 3:2 ratio to receive either ISA (10 mg/kg weekly in Cycle 1 then once every 2 weeks thereafter) in combination with carfilzomib (56 mg/m2 on Days [d] 1, 2, 8, 9, 15, and 16, 20 mg/m2 on d 1 and 2 of Cycle 1) and dexamethasone (20 mg on d 1, 2, 8, 9, 15, 16, 22, and 23) or Kd in 28-d cycles until disease progression, pt choice, or unacceptable toxicity. The primary endpoint is progression-free survival (PFS) according to International Myeloma Working Group Criteria. Key secondary endpoints include overall response rate, rate of very good partial response or greater, minimal residual disease negativity rate, complete response rate, and overall survival. Other secondary endpoints include safety, duration of response, time to progression, PFS2, pharmacokinetics, and quality of life. Safety evaluations will include adverse events and laboratory parameters, vital signs, and physical examination. The IKEMA study is currently enrolling pts; recruitment is planned in 16 countries worldwide. Study funding: Sanofi. Clinical trial information: NCT03275285.