J&J claims another second-line Tecvayli win
Majestec-9, in post-Darzalex multiple myeloma, is the latest success.
Majestec-9, in post-Darzalex multiple myeloma, is the latest success.
Soon after wowing ASH with Tecvayli plus Darzalex in Majestec-3 in second-line multiple myeloma, Johnson & Johnson has claimed another hit with this anti-BCMA T-cell engager. The Majestec-9 trial also enrolled subjects with one to three prior lines of therapy, but focused on the slightly different setting of post-Darzalex patients.
Here, Tecvayli monotherapy reduced the risk of disease progression or death by 71%, and the risk of death by 40%, versus standard of care: Pomalyst, Velcade and dexamethasone, or Kyprolis plus dexamethasone.
Full results from Majestec-9, which was unblinded early based on data from this first interim analysis, will be presented at an upcoming medical meeting, J&J said on Wednesday.
One detail of interest will be the exact proportion of patients that were refractory to (rather than relapsed after receiving) anti-CD38 MAbs like Darzalex who, J&J said, made up the majority of the study population.
The company didn’t disclose specific filing plans, but has previously indicated its desire to move quickly with Tecvayli, which currently has accelerated approval for fifth-line multiple myeloma.
Darzalex combo
Another nod might come soon for a Tecvayli-Darzalex combo, based on Majestec-3, which enrolled patients who were naive or sensitive to anti-CD38 Mabs, and found an 83% reduction in the risk of progression or death versus Darzalex plus dexamethasone and either Pomalyst or Velcade.
OS was statistically significantly improved with Tecvayli plus Darzalex, with a hazard ratio of 0.46. J&J disclosed in December that it had filed Tecvayli-Darzalex with the FDA, although the company hasn’t provided a PDUFA date.
One reason for caution could be a relatively high rate of fatal infections, but these appear to be less problematic after more stringent prophylactic measures were introduced.
Talvey combo?
This year could also see the readout of another early-line Tecvayli trial, Monumental-6 – like Majestec-9, this includes patients who have previously received Darzalex and Revlimid.
However, Monumental-6 tests Tecvayli alongside J&J’s GPRC5D-targeting T-cell engager Talvey, as well as a Talvey-Pomalyst combo. If this succeeds, it could raise questions about whether Tecvayli or Talvey should be used in the post-Darzalex population.
J&J is also challenging Tecvayli with another of its projects, the trispecific BCMA x GPRC5D T-cell engager ramantamig.
Phase 3 trials of Tecvayli in multiple myeloma
| Trial | Line | Regimen | Primary endpoint(s) | Note |
|---|---|---|---|---|
| Majestec-3 | 1-3 prior lines; naive or sensitive to an anti-CD38 MAb | + Darzalex, vs DPd or DVd | PFS | Data at ASH 2025: 83% reduction in risk of progression/death; 54% reduction in risk of death |
| Majestec-9 | 1-3 prior lines; post-anti-CD38 MAb & Revlimid | Monotx, vs PVd or Kd | PFS | Topline data Jan 2026: 71% reduction in risk of progression/death; 40% reduction in risk of death |
| Monumental-6 | 1 to 4 prior lines; post-anti-CD38 MAb & Revlimid | + Talvey + d, or Talvey + Pd, vs EPd or PVd | PFS | Completes Apr 2026 |
| Majestec-4* | 1st-line; post-ASCT | +/- R, vs R | PFS, 12mth MRD-ve CR | Completes Apr 2028 |
| Majestec-7 | 1st-line; ASCT-ineligible | + DR, or Talvey + DR, vs DRd | PFS, 12mth MRD-ve CR | Completes Apr 2031 |
Notes: *investigator-sponsored trial; D=Darzalex; d=dexamethasone; E=Empliciti; K=Kyprolis; P=Pomalyst; R=Revlimid; V=Velcade. Source: OncologyPipeline.
177
