J&J's multiple myeloma duo aces phase 3 trial

Two of Johnson & Johnson's multiple myeloma therapies – Tecvayli and Talvey – have dramatically improved overall survival when used as a combination therapy.

In the phase 3 MonumenTAL-6 trial, Tecvayli (teclistamab) and Talvey (talquetamab) cut the risk of disease progression or death by 89% compared to standard-of-care combinations used as second- to fifth-line multiple myeloma therapies, and the risk of death by 62%.

This is the first phase 3 trial looking at the combination of the two bispecific T-cell engagers (TCEs), respectively targeting BCMA and GPRC5D in patients with relapsed/refractory multiple myeloma, according to J&J.

Tecvayli on its own has already shown impressive efficacy as a second-line therapy and is approved in that setting as a combination with J&J and Genmab's anti-CD38 antibody Darzalex Faspro (daratumumab/hyaluronidase). Now, the addition of first-in-class Talvey – currently approved as a fifth-line or later therapy for multiple myeloma – has produced unprecedented results for bispecific antibody therapies for blood cancer.

The strength of the result has led to a recommendation from the trial's independent data monitoring committee to unblind it at this first interim analysis.

MonumenTAL-6 also included an arm looking at Tecvayli plus pomalidomide, which also met the primary objective of improving progression-free survival (PFS) compared to the control therapies – Bristol Myers Squibb/AbbVie's Empliciti (elotuzumab), pomalidomide and dexamethasone or Takeda's Velcade (bortezomib) pomalidomide and dexamethasone (Pvd) – but was less effective than Tecvayli plus Talvey.

Emory University School of Medicine's Ajay Nooka, one of the investigators in MonumenTAL-6, said the results "add to a growing body of phase 3 evidence evaluating the survival outcomes associated with the early use of immunotherapy doublets in the treatment journey."

He added: "Tecvayli and Talvey together generated deep and durable responses, demonstrating what's possible by targeting BCMA and GPRC5D at the same time, and further reinforcing the potential of this off-the-shelf regimen to improve outcomes for patients across practice settings."

J&J has said it plans to share the data with regulators with a view to expanding the labels for both bispecifics, which are already delivering impressive sales growth. Tecvayli brought in $202 million in the first quarter of this year, up 33.5%, while Talvey rocketed nearly 77% to $152 million.

J&J has also reported positive results from the MajesTEC-9 trial, in which second-line or later monotherapy with Tecvayli reduced PFS by 71% and OS by 40% compared to standard care in a post-Darzalex patient population.

J&J has also filed for approval of the bispecific in those settings, which could also expand its second-line label and give oncologists an additional treatment option. Meanwhile Talvey in combination with Darzalex Faspro showed efficacy in MonumenTAL-3 as a second-line regimen with or without pomalidomide.