Bristol shows its alnuctamab hand

With two BCMA-targeting T-cell-engager bispecifics already boasting US accelerated approvals, and a third seeking a similar nod, how can others compete? Bristol Myers Squibb and AbbVie haven’t said they would pursue the accelerated pathway for alnuctamab and ABBV-383 respectively, and both are now in formal phase 3 trials. The unveiling of alnuctamab’s phase 3 Alumminate study has revealed that this will already take the Bristol project into patients with as early as second-line multiple myeloma: the clinicaltrials.gov entry’s inclusion criteria mandate “at least one ... prior line of therapy” as long as that includes Revlimid and an anti-CD38 MAb. This suggests a more aggressive strategy than AbbVie is taking: that company’s TeneoOne-derived ABBV-383 will enter phase 3 in a more typical relapsed-refractory setting, with patients having to have received at least two prior therapy lines. The two approved drugs, J&J’s Tecvayli and Pfizer’s Elrexfio, are in several phase 3 studies in settings as early as first line and early maintenance, some of which might be capable of confirming their accelerated approvals. Meanwhile, Regeneron is seeking accelerated approval for linvoseltamab in the fourth line or later, and a confirmatory phase 3 is under way in third-line use.

Phase 3 trials of anti-BCMA T-cell engager MAbs

Notes: *2022 US accelerated approved for 5L use, Majestec-1 trial; **2023 accelerated approved for 5L use, Magnetismm-3 trial; ^Dec 2023 filing for accelerated approval, 4L+ Linker-MM1 trial, yet to be accepted. PI=proteasome inhibitor, eg Velcade or Kyprolis. IMID=Revlimid or Pomalyst. ASCT=autologous stem cell transplant. Source: OncologyPipeline & company statements.