Just months after reporting promising efficacy data in a phase 1 study of BMS-986393, Bristol Myers Squibb has unveiled plans to take this anti-GPRC5D Car-T therapy into pivotal development. The Quintessential-2 study, against Darzalex, Pomalyst, Kyprolis plus dexamethasone in second to fourth-line multiple myeloma, is to begin in February, a new listing on the clinicaltrials.gov registry reveals. The move is significant not only for its speed, but also because the company has made cuts elsewhere in its multiple myeloma pipeline, most notably discontinuing a phase 3 anti-BCMA T-cell engager, alnuctamab, citing changed business objectives and an “evolving landscape”; this appeared to be a clear reference to the large number of approved anti-BCMA drugs, most importantly the Car-T therapies Carvykti and Abecma, and the T-cell engagers Tecvayli and Elrexfio. The GPRC5D space is somewhat less crowded, though Johnson & Johnson’s Talvey (another T-cell engager) is approved. In phase 1 BMS-986393 yielded an 88% ORR and 45% CR rate – better than Talvey on a cross-trial basis – though one patient died from drug-related cytokine release. Bristol is separately continuing to develop BMS-986453, a Car-T therapy that intriguingly hits BCMA as well as GPRC5D. Selected Bristol work in multiple myelomaProjectMechanismStatusRevlimidCelmodApprovedPomalystCelmodApprovedAbecmaAnti-BCMA Car-TApprovedIberdommideCelmodPh3MezigdomideCelmodPh3BMS-986393Anti-GPRC5D Car-TPh3 starts Feb 2025BMS-986453Anti-BCMA x GPRC5D Car-TPh1MCARH109Anti-GPRC5D Car-TPh1 investigator-sponsored trial onlyAlnuctamabAnti-BCMA T-cell engagerDiscontinued in ph3Orvacabtagene autoleucelAnti-BCMA Car-TDiscontinued in ph2FCARH143Anti-BCMA Car-TPh1 completed; no further workbb21217Anti-BCMA Car-TPh1 completed; no further workMCARH171Anti-BCMA Car-TDiscontinued in ph1Ispectamab debotansineAnti-BCMA ADCDiscontinued in ph1Source: OncologyPipeline.
Just months after reporting promising efficacy data in a phase 1 study of BMS-986393, Bristol Myers Squibb has unveiled plans to take this anti-GPRC5D Car-T therapy into pivotal development. The Quintessential-2 study, against Darzalex, Pomalyst, Kyprolis plus dexamethasone in second to fourth-line multiple myeloma, is to begin in February, a new listing on the clinicaltrials.gov registry reveals. The move is significant not only for its speed, but also because the company has made cuts elsewhere in its multiple myeloma pipeline, most notably discontinuing a phase 3 anti-BCMA T-cell engager, alnuctamab, citing changed business objectives and an “evolving landscape”; this appeared to be a clear reference to the large number of approved anti-BCMA drugs, most importantly the Car-T therapies Carvykti and Abecma, and the T-cell engagers Tecvayli and Elrexfio. The GPRC5D space is somewhat less crowded, though Johnson & Johnson’s Talvey (another T-cell engager) is approved. In phase 1 BMS-986393 yielded an 88% ORR and 45% CR rate – better than Talvey on a cross-trial basis – though one patient died from drug-related cytokine release. Bristol is separately continuing to develop BMS-986453, a Car-T therapy that intriguingly hits BCMA as well as GPRC5D.
Selected Bristol work in multiple myeloma
| Project | Mechanism | Status |
|---|
| Revlimid | Celmod | Approved |
| Pomalyst | Celmod | Approved |
| Abecma | Anti-BCMA Car-T | Approved |
| Iberdommide | Celmod | Ph3 |
| Mezigdomide | Celmod | Ph3 |
| BMS-986393 | Anti-GPRC5D Car-T | Ph3 starts Feb 2025 |
| BMS-986453 | Anti-BCMA x GPRC5D Car-T | Ph1 |
| MCARH109 | Anti-GPRC5D Car-T | Ph1 investigator-sponsored trial only |
| Alnuctamab | Anti-BCMA T-cell engager | Discontinued in ph3 |
| Orvacabtagene autoleucel | Anti-BCMA Car-T | Discontinued in ph2 |
| FCARH143 | Anti-BCMA Car-T | Ph1 completed; no further work |
| bb21217 | Anti-BCMA Car-T | Ph1 completed; no further work |
| MCARH171 | Anti-BCMA Car-T | Discontinued in ph1 |
| Ispectamab debotansine | Anti-BCMA ADC | Discontinued in ph1 |
