Pivotal T-cell engager readouts approach

Regeneron’s recent US accelerated approval for the BCMA-targeted T-cell engager Lynozyfic was better late than never, but the group still lags behind its rivals, Johnson & Johnson’s Tecvayli and Pfizer’s Elrexfio.

The next few months should see pivotal data on the J&J and Pfizer drugs in the relapsed setting, which could confirm and potentially expand their uses. Meanwhile, in the front line Regeneron’s product is so far only in an investigator-sponsored trial, while various J&J and Pfizer studies are well under way.

A Regeneron spokesperson told ApexOnco that “additional trials are planned”, and the company also appears to be making a push into disease precursors like smouldering multiple myeloma and monoclonal gammopathy of undetermined significance (MGUS). However, use of T-cell engagers in asymptomatic conditions could be controversial, especially given side effects like cytokine release syndrome and neurological toxicity.

Confirmatory

Elrexfio, Lynozyfic and Tecvayli all have FDA accelerated approvals for fifth-line multiple myeloma following a proteasome inhibitor, immunomodulatory agent, and anti-CD38 monoclonal antibody such as J&J’s Darzalex.

The upcoming readouts could inch them into earlier settings. First up could be data from Majestec-3, which is slated to complete in August. This study is evaluating Tecvayli plus Darzalex in patients who have received a proteasome inhibitor and Revlimid.

Phase 3 trials of approved BCMA T-cell engagers in relapsed myeloma

Notes: All studies have PFS as primary efficacy endpoint; *investigator-sponsored trial; ASCT=autologous stem cell transplant; D=Darzalex; d=dexamethasone; E=Empliciti; K=Kyprolis; P=Pomalyst; R=Revlimid; V=Velcade. Source: OncologyPipeline & clinicaltrials.gov.

Meanwhile, Elrexfio’s Magnetismm-5 study, in patients who previously received two of the drug classes above (known as double-class exposed), could yield results by the end of this year, Pfizer said during the Goldman Sachs healthcare conference in June.

Primary completion of that trial has been pushed back from August to December 2025, and a part 3 was also added to assess the effect of “increased measures” to protect against risk of infection while on Elrexfio alone or in combination with Darzalex. This doesn’t seem like a good sign, although all the approved BCMA T-cell engagers carry warnings for infection.

Pfizer has also delayed the primary completion date of its Elrexfio monotherapy study, Magnetismm-32, from December 2025 to August 2026.

And the Majestec-9 study of Tecvayli now completes in February 2026, versus October 2025 previously. J&J is also testing Tecvayli plus its GPRC5D-targeting T-cell engager Talvey in relapsed disease in Monumental-6, results from which could be available next year.

Meanwhile, Regeneron’s confirmatory trial, Linker-MM3, only completed enrolment earlier this year, so has a way to go.

Precursor conditions

Still, Regeneron seems to be making a bigger push in smouldering multiple myeloma and the even earlier-stage MGUS. Two Regeneron-sponsored phase 2s are under way here, while J&J and Pfizer’s efforts are limited to investigator-sponsored studies.

The academic Immuno-Prism platform study reported a 100% response rate among 12 Tecvayli-treated patients at ASH 2023, although not much seems to have happened here since. A spokesperson for J&J told ApexOnco that the company expects more results from Immuno-Prisom "in the next several months". The current standard of care in smouldering disease is watchful waiting.

The group’s attention here is likely on Darzalex, which is due an FDA decision soon, although exact timelines are unclear. Approval is expected following a positive adcom vote in May, although the concept of treating an asymptomatic disease precursor could still be controversial.

Moving these drugs into MGUS, which might never progress to active multiple myeloma, promises to be even more contentious.

Phase 3 trials of BCMA T-cell engagers in early multiple myeloma

Notes: *investigator-sponsored trial; ASCT=autologous stem cell transplant; MGUS=monoclonal gammopathy of undetermined significance; D=Darzalex; d=dexamethasone; R=Revlimid; V=Velcade. Source: OncologyPipeline & clinicaltrials.gov.