Bristol seeks another celmod use
Golcadomide will begin a new pivotal trial in follicular lymphoma.
Golcadomide will begin a new pivotal trial in follicular lymphoma.
As the first pivotal readouts approach for Bristol Myers Squibb’s “celmod” projects the company will start another phase 3 trial of one of its contenders in the coming months, a recent clinicaltrials.gov listing reveals.
The new study, Golseek-4, will test golcadomide in second-line follicular lymphoma, adding to the ongoing Golseek-1 trial in first-line large B-cell lymphoma. Bristol’s other celmods, iberdomide and mezigdomide, are being evaluated in multiple myeloma.
Iberdomide is expected to yield phase 3 data first, with results from the Excaliber-RRMM trial slated for this year, according to Bristol’s fourth-quarter earnings presentation. Mezigdomide shouldn’t be too far behind, with the Successor-1 and 2 trials both set to read out in 2026.
Bristol’s pivotal-stage cereblon E3 ligase modulators (celmods)
| Project | Trial | Setting | Regimen | Timing |
|---|---|---|---|---|
| Golcadomide (CC-99282/ BMS-986369) | Golseek-1 | 1st-line LBCL | + Rituxan + chemo, vs Rituxan + chemo | Data due 2028 |
| Golseek-4 | 2nd-line follicular lymphoma | + Rituxan, vs Ritxuan + Revlimid or chemo | To begin Jul 2025; primary completion Jul 2030 | |
| Iberdomide (CC-220) | Excaliber-RRMM | 2nd-line multiple myeloma | + Darzalex + dexamethasone, vs Darzalex + Velcade + dexamethasone | Data due 2025 |
| Excaliber-Maintenance | 1st-line multiple myeloma maintenance | Vs Revlimid maintenance following ASCT | Data due 2029 | |
| Mezigdomide (CC-92480/ BMS-986348) | Successor-1 | 2nd-line multiple myeloma | + Velcade + dexamethasone, vs Pomalyst + Velcade + dexamethasone | Data due 2026 |
| Successor-2 | 2nd-line multiple myeloma | + Kyprolis + dexamethasone, vs Kyprolis + dexamethasone | Data due 2026 |
Source: OncologyPipeline & clinicaltrials.gov.
Bristol hopes that celmods (short for cereblon E3 ligase modulators) could help it weather the loss of patent exclusivity on its established multiple myeloma franchise, gained via the group’s $74bn purchase of Celgene in 2019.
For instance, Revlimid’s patents are set to expire next year, but Dr Reddy’s is already selling a generic version on a “volume-limited” basis. Revlimid revenues totalled $5.8bn in 2024, down 5% year-on-year. Pomalyst is expected to face generics in 2026.
Celmods are small molecules that bind to the cereblon protein and lead to the degradation of certain substrates, for instance Ikaros and Aiolos. They’re said to be more potent and selective than imids like Revlimid and Pomalyst, which have only relatively recently been found to work in this way too.
Each celmod is apparently optimised for a different disease setting. Bristol is positioning iberdomide as a replacement for Revlimid, and mezigdomide as a Pomalyst follow-on – but the projects are far from the group’s only shots in multiple myeloma.
Development of golcadomide, meanwhile, has focused on lymphoma. A clue about that project’s performance in the relatively indolent follicular setting could come from the phase 2 Golseek-2 trial, due to yield data next year – although that’s in first-line disease, while the upcoming Golseek-4 trial will enrol second-line patients.
1659
