The FDA has accepted a new drug application (NDA) seeking the approval of mezigdomide (CC-92480) in combination with carfilzomib (Kyprolis) and dexamethasone (MeziKd) for the treatment of patients with relapsed or refractory multiple myeloma.1
The regulatory agency assigned a Prescription Drug User Fee Act target action date of May 13, 2027.
The application was based on
“The FDA’s acceptance of our application for mezigdomide highlights the continued momentum of our targeted protein degradation programs, as we now have two distinct agents under review in relapsed or refractory multiple myeloma, which remains a persistent disease,” Cristian Massacesi, MD, executive vice president, chief medical officer, and head of development at Bristol Myers Squibb, stated in the news release.1 “We’re rapidly progressing the development of our CELMoD pipeline and are committed to leveraging this platform to bring the next wave of advances for patients in both hematologic malignancies and solid tumors.”
Mezigdomide is an oral
SUCCESSOR-2 was a multicenter, randomized, open-label phase 3 study evaluating MeziKd vs Kd in patients with relapsed/refractory multiple myeloma who had received at least 1 prior line of therapy, including prior lenalidomide (Revlimid) and an anti-CD38 monoclonal antibody.1,2
Dose optimization was conducted in stage 1, with the 1.0-mg mezigdomide dose selected for stage 2.2 The confirmatory analysis group comprised 479 patients who were randomly assigned 3:2. In the MeziKd arm, patients received mezigdomide at 1.0 mg orally once daily on days 1 to 21 of each 28-day cycle, carfilzomib at 56 mg/m² intravenously, and dexamethasone at 40 mg.
The primary end point was PFS per independent review committee assessment. Key secondary end points included overall survival (OS), overall response rate (ORR), duration of response (DOR), time to progression, time to next treatment, minimal residual disease negativity, and health-related quality of life.1
The PFS benefit with MeziKd was consistent across all prespecified subgroups, regardless of prior therapy, age, refractory status, cytogenetic risk, or the presence of extramedullary disease.2
Additionally, MeziKd generated an ORR of 80.2% compared with 53.4% for Kd, including a very good partial response or better rate of 60.1% vs 30.9%, and a complete response or better rate of 26.7% vs 8.9%. The 12-month DOR rate was 72% (95% CI, 65%-78%) with MeziKd vs 54% (95% CI, 41%-66%) with Kd.
MeziKd also improved time to second progression (PFS2), with a median of 23.6 months vs 13.0 months for Kd (HR, 0.53; 95% CI, 0.39-0.72).
OS data were immature at the time of a planned futility analysis; deaths occurred in 21.5% (62/288) of patients in the MeziKd arm and 26.7% (51/191) in the Kd arm, yielding an OS HR of 0.79 (95% CI, 0.54-1.15) that favored MeziKd with no crossover of the curves.
The safety profile of MeziKd was consistent with prior mezigdomide studies and the known profiles of the individual agents, with no new safety signals.1,2
Grade 3/4 treatment-emergent adverse effects (TEAEs) occurred in 83.7% of patients treated with MeziKd (n = 288) vs 56.5% of those treated with Kd (n = 186).2 Neutropenia was the most common grade 3/4 TEAE, occurring at any grade in 69.1% of patients in the MeziKd arm and at grade 3/4 in 61.1%; febrile neutropenia occurred in 8.3% of patients at any grade. Only 1 patient discontinued MeziKd because of neutropenia. Additional grade 3/4 hematologic events with MeziKd included thrombocytopenia (39.2%) and anemia (26.0%). Grade 3/4 venous thromboembolism occurred in 2.8% of MeziKd-treated patients vs 0.5% of Kd-treated patients.
Grade 5 TEAEs were reported in 7.3% of the MeziKd arm and 4.3% of the Kd arm, the majority of which occurred in the context of myeloma progression. Any infection occurred in 72.9% of MeziKd-treated patients, and the incidence of fatal infections was low at 2.4% with MeziKd vs 1.1% with Kd.
