Mezigdomide (CC-92480)

Overview

Mezigdomide (CC-92480) is a novel cereblon E3 ligase modulator (CELMoD) agent designed for rapid, maximal degradation of Ikaros and Aiolos. In vitro, it has enhanced antiproliferative and tumoricidal activity in MM cell lines, including those resistant to lenalidomide (LEN) and pomalidomide (POM), with strong immune stimulatory activity.

SparkCures ID 307
Developed By Celgene Corporation, a wholly owned subsidiary of Bristol Myers Squibb
Generic Name Mezigdomide (CC-92480)
Additional Names CC-92480
Treatment Classifications

Clinical Trials

All Clinical Trials

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Untreated / Newly Diagnosed Multiple Myeloma

The following is a listing of clinical trials for patients with multiple myeloma who have been newly diagnosed or have not yet received treatment.

Early Relapse Multiple Myeloma

The following is a listing of clinical trials for patients with multiple myeloma who have received one to two prior lines of therapy.

Late Relapse Multiple Myeloma

The following is a listing of clinical trials for patients with multiple myeloma who have received three or more prior lines of therapy.

Smoldering Myeloma
Monoclonal Gammopathy of Undetermined Significance (MGUS)

Published Results

Mezigdomide (CC-92480), a Potent, Novel Cereblon E3 Ligase Modulator (CELMoD), Combined with Dexamethasone (DEX) in Patients (pts) with Relapsed/Refractory Multiple Myeloma (RRMM): Preliminary Results from the Dose-Expansion Phase of the CC-92480-MM-001 Trial

December 11, 2022

As of May 24, 2022, 101 pts had received MEZI + DEX at the RP2D. Median age was 67 (range 42–85) years, median time since initial diagnosis was 7.4 (1.1–37.0) years, and 20.8% of pts had ISS stage III at study entry. Plasmacytomas were present in 38.6% of pts and 36/101 pts had high-risk cytogenetics (55/101 pts were not evaluable). Median number of prior regimens was 6 (range 3–15). Prior therapies included stem cell transplantation (77.2%) and anti-BCMA therapy (29.7%) (Table 1). All pts were refractory to last myeloma regimen and triple-class refractory (refractory to an IMiD agent [LEN/POM], a PI, and an anti-CD38 mAb), and 39.6% of pts were refractory to LEN, POM, ≥ 2 PIs, and an anti-CD38 mAb. Median follow-up was 5.8 (range 0.5–19.0) months, with a median number of 4 (1–18) cycles received and 23 (22.8%) pts continued on treatment. The main reason for discontinuation was progressive disease (50.5%).

ORR was 39.6%, with 2 (2.0%) stringent complete responses, 3 (3.0%) complete responses, 18 (17.8%) very good partial responses, and 17 (16.8%) partial responses (Table 2). While data are not yet mature, the preliminary median duration of response was 8.3 (95% confidence interval [CI] 5.4–not reached) months and median progression-free survival was 4.6 (95% CI 3.2–6.3) months. ORR was 30.8% in pts with plasmacytomas (N = 39) and 50.0% in pts with prior anti-BCMA therapy (N = 30).

Grade (Gr) 3/4 treatment-emergent adverse events (TEAEs) were reported in 90 (89.1%) pts. Most frequent (≥ 20% pts) hematologic Gr 3/4 TEAEs were neutropenia (74.3%, with 14.9% febrile neutropenia), anemia (32.7%), and thrombocytopenia (25.7%). Gr 3/4 infections were observed in 32.7% of pts; Gr 3/4 pneumonia and COVID-19 were present in 9.9% and 5.0% of pts, respectively. The occurrence of other Gr 3/4 non-hematologic TEAEs was generally low, including gastrointestinal disorders (5.9%), fatigue (4.0%), and rash (1.0%). Seventy-two (71.3%) pts and 29 (28.7%) had MEZI dose interruptions and reductions due to TEAEs, respectively; 6 (5.9%) pts discontinued MEZI due to TEAEs, with 1 pt due to hematological TEAEs.

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