J&J claims a Tecvayli/Darzalex combo win

Johnson & Johnson hopes to consolidate the stranglehold it has on the multiple myeloma market, on Thursday toplining the first phase 3 win for a combination of Tecvayli and Darzalex.

The company said the first interim analysis of the Majestec-3 trial, in patients who had received one to three prior therapy lines, had returned a positive result on both the primary endpoint, progression-free survival, and the key secondary of overall survival. In the study Tecvayli and Darzalex Faspro were pitted against Darzalex with dexamethasone, plus either Pomalyst or Velcade.

J&J, which believes that the combo could become a new standard of care, is saving the detailed results for an upcoming medical meeting. The company also plans to submit the data to regulators "as fast as we're able", J&J oncology’s vice-president of global medical affairs, Mark Wildgust, told ApexOnco.

Fifth to second-line?

Tecvayli, a BCMA-targeting T-cell engager, currently has US accelerated approval for fifth-line multiple myeloma. Meanwhile, the Genmab-partnered anti-CD38 MAb Darzalex is increasingly being used first line as part of various combos, and is also awaiting an FDA decision in a disease precursor, smouldering multiple myeloma.

Looking ahead, J&J also has hopes for Tecvayli plus Darzalex in first-line disease; the Majestec-7 study, in stem cell transplant-ineligible patients, is testing both this combo, and Darzalex alongside J&J’s GPRC5D-targeting T-cell engager Talvey.

At ASCO 2024 the company presented results from a safety run-in phase, which showed a 92% ORR with Tecvayli plus Darzalex plus Revlimid. 

J&J also recently reported data from the phase 2 investigator-sponsored Majestec-5 trial, saying a Tecvayli/Darzalex combo led to a 100% ORR in first-line patients. Still, this is a slightly different, transplant-eligible setting.

J&J is additionally evaluating a Tecvayli/Talvey combo, in the Monumental-6 trial in relapsed multiple myeloma, which is due to complete next year.

The company is already looking to the next horizon though, with the trispecific T-cell engager JNJ-79635322, which hits both BCMA and GPRC5D. J&J reckons this project could be more potent than a Tecvayli/Talvey combo; early data recently presented at ASCO spurred claims of Car-T-like efficacy. 

Meanwhile, AbbVie is developing a trispecific T-cell engager targeting BCMA and CD38, ISB 2001, via a $700m deal with Glenmark.

Phase 3 Tecvayli combo trials in multiple myeloma

Note: D=Darzalex; d=dexamethasone; E=Empliciti; P=Pomalyst; R=Revlimid; V=Velcade. Source: OncologyPipeline & clinicaltrials.gov.