Contributions
Abstract: PB2184
Type: Publication Only
Background
Multiple myeloma remains an incurable disease requiring multiple lines of therapy, in which carfilzomib-based treatments are a standard of care. Isatuximab (ISA), an anti-CD38 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 with RRMM.
Aims
This Phase III, prospective, randomized, open-label study (NCT03275285; IKEMA) will evaluate the clinical benefit of ISA in combination with Kd vs Kd alone in patients with RRMM.
Methods
Patients with RRMM who have received 1–3 prior lines of therapy will be enrolled. Patients who have received prior carfilzomib therapy, have primary refractory disease, or have free light chain measurable disease only will be excluded. Approximately 300 patients will be randomized according to 2 stratification factors (prior lines of therapy: 1 vs >1; revised International Staging System [R-ISS] criteria 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 Kd (carfilzomib [56 mg/m2 on Days 1, 2, 8, 9, 15, and 16; 20 mg/m2 on Days 1 and 2 of Cycle 1] and dexamethasone [20 mg on Days 1, 2, 8, 9, 15, 16, 22, and 23]) or Kd in 28-day cycles until disease progression (PD), patient choice, or unacceptable toxicity. Patients will provide written, informed consent before participation in the trial.
The primary endpoint is progression-free survival (PFS), defined as the time from the date of randomization to the date of first documentation of PD (according to International Myeloma Working Group Criteria) or death. Comparison between arms will be conducted through a log-rank test procedure stratified by number of previous lines of therapy and R-ISS. 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 (defined as the time from randomization to the time of second PD or death), pharmacokinetics, and quality of life. Safety evaluations will include adverse events and laboratory parameters, vital signs, and physical examination.
Results
The IKEMA study is currently enrolling patients; recruitment is planned in 16 countries worldwide.
Conclusion
This Phase III, randomized, multicenter study will provide an evaluation of the efficacy and safety of ISA added to Kd standard of care in patients with RRMM.
Funding: Sanofi
Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical
Keyword(s): CD38, Monoclonal antibody, Multiple Myeloma
Abstract: PB2184
Type: Publication Only
Background
Multiple myeloma remains an incurable disease requiring multiple lines of therapy, in which carfilzomib-based treatments are a standard of care. Isatuximab (ISA), an anti-CD38 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 with RRMM.
Aims
This Phase III, prospective, randomized, open-label study (NCT03275285; IKEMA) will evaluate the clinical benefit of ISA in combination with Kd vs Kd alone in patients with RRMM.
Methods
Patients with RRMM who have received 1–3 prior lines of therapy will be enrolled. Patients who have received prior carfilzomib therapy, have primary refractory disease, or have free light chain measurable disease only will be excluded. Approximately 300 patients will be randomized according to 2 stratification factors (prior lines of therapy: 1 vs >1; revised International Staging System [R-ISS] criteria 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 Kd (carfilzomib [56 mg/m2 on Days 1, 2, 8, 9, 15, and 16; 20 mg/m2 on Days 1 and 2 of Cycle 1] and dexamethasone [20 mg on Days 1, 2, 8, 9, 15, 16, 22, and 23]) or Kd in 28-day cycles until disease progression (PD), patient choice, or unacceptable toxicity. Patients will provide written, informed consent before participation in the trial.
The primary endpoint is progression-free survival (PFS), defined as the time from the date of randomization to the date of first documentation of PD (according to International Myeloma Working Group Criteria) or death. Comparison between arms will be conducted through a log-rank test procedure stratified by number of previous lines of therapy and R-ISS. 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 (defined as the time from randomization to the time of second PD or death), pharmacokinetics, and quality of life. Safety evaluations will include adverse events and laboratory parameters, vital signs, and physical examination.
Results
The IKEMA study is currently enrolling patients; recruitment is planned in 16 countries worldwide.
Conclusion
This Phase III, randomized, multicenter study will provide an evaluation of the efficacy and safety of ISA added to Kd standard of care in patients with RRMM.
Funding: Sanofi
Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical
Keyword(s): CD38, Monoclonal antibody, Multiple Myeloma