FDA Accepts NDA for Mezigdomide Combo in R/R Multiple Myeloma

The FDA has accepted a new drug application (NDA) seeking approval for the investigational oral cereblon E3 ligase modulator (CELMoD) mezigdomide plus carfilzomib (Kyprolis) and dexamethasone (MeziKd) for patients with relapsed/refractory multiple myeloma, according to a press release from the developer, Bristol Myers Squibb.¹ The agency has assigned a Prescription Drug User Fee Act date of May 13, 2027, for approving the mezigdomide-based combination in this multiple myeloma population.

What data support mezigdomide in relapsed/refractory multiple myeloma?

The NDA was supported by findings from the phase 3 SUCCESSOR-2 trial (NCT05552976), which evaluated the safety and efficacy of MeziKd vs Kd alone among those with relapsed/refractory multiple myeloma. Investigators previously presented findings from the SUCCESSOR-2 trial at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting and published them in The Lancet.^2,3

Data from the trial showed a median progression-free survival (PFS) of 18.0 months with MeziKd vs 8.3 months with Kd alone (HR, 0.48; 95% CI, 0.36-0.63; P <.0001). Investigators noted a PFS benefit with MeziKd across all prespecified subgroups, which included patients with high-risk cytogenetics, extramedullary disease, and soft-tissue plasmacytomas.

The overall response rate (ORR) was 80.2% with MeziKd and 53.4% with Kd, with corresponding complete response (CR) or better rates of 26.7% vs 8.9%. A planned futility analysis of overall survival (OS) demonstrated a favorable trend in the MeziKd arm (HR, 0.79; 95% CI, 0.54-1.15).

The safety profile of MeziKd in the SUCCESSOR-2 trial was comparable with prior reports of mezigdomide, as investigators reported no new safety signals. The most common grade 3/4 adverse effect (AE) was neutropenia, which occurred in 61.1% of patients in the MeziKd arm and 9.1% of the Kd arm. Additionally, grade 5 treatment-emergent AEs were reported in 7.3% and 4.3% of each respective arm; most occurred in the context of disease progression.

“The FDA’s acceptance of our application for mezigdomide highlights the continued momentum of our targeted protein degradation programs, as we now have 2 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 press 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.”

What is mezigdomide, and how was SUCCESSOR-2 designed?

Developers designed mezigdomide as an orally available CeLMoD agent leveraging a protein degradation platform built for maximal and rapid degradation of Ikaros and Aiolos target proteins. The agent’s design may facilitate higher killing of multiple myeloma cells and immune stimulation. Additionally, pre-clinical data have demonstrated the agent’s ability to enhance T cell function while reinvigorating an exhausted immune system.

In the multicenter phase 3 SUCCESSOR-2 trial, 479 patients were randomly assigned 3:2 to receive MeziKd (n = 288) or Kd (n = 191). Patients in the experimental arm received mezigdomide at 1.0 mg orally once daily on days 1 through 21 of each 28-day cycle; carfilzomib at 56 mg/m² intravenously on days 1, 8, and 15 of the first cycle and days 1 and 15 in later cycles; and dexamethasone at 40 mg on days 8, 15, and 22.

The trial’s primary end point was PFS. Key secondary end points included OS, ORR, duration of response, time to progression, minimal residual disease negativity, and health-related quality of life.

References

1. U.S. Food and Drug Administration accepts Bristol Myers Squibb's new drug application for mezigdomide in patients with relapsed or refractory multiple myeloma. News release. Bristol Myers Squibb. July 13, 2026. Accessed July 13, 2026. https://tinyurl.com/5fp9dzmz
2. Richardson PG, Schjesvold F, Fu C, et al. Mezigdomide, carfilzomib, and dexamethasone vs carfilzomib and dexamethasone in relapsed/refractory multiple myeloma: results from the phase 3 SUCCESSOR-2 trial. J Clin Oncol. 2026;44(suppl 17):LBA7506. doi:10.1200/JCO.2026.44.17_suppl.LBA7506
3. Dimopoulos MA, Schjesvold F, Fu C, et al. Mezigdomide, carfilzomib, and dexamethasone versus carfilzomib and dexamethasone in patients with relapsed or refractory multiple myeloma (SUCCESSOR-2): a phase 3, open-label, randomised controlled trial. The Lancet. Published online June 14, 2026. doi:10.1016/S0140-6736(26)01088-3