Phase 3 trial findings support myeloma treatment regimen

An approved treatment regimen using the oral therapy Zenbexus (iberdomide) can reduce the risk of disease progression among people with hard-to-treat multiple myeloma, according to top-line data from a Phase 3 clinical trial.

The EXCALIBER-RRMM (NCT04975997) trial enrolled more than 800 people with myeloma that had either failed to respond to or come back after one or two previous lines of treatment. All participants received Darzalex Faspro (daratumumab and hyaluronidase-fihj) and the corticosteroid dexamethasone, in combination with either Zenbexus or Velcade (bortezomib), another approved therapy for myeloma.

The study had two main goals. The first was to assess whether the Zenbexus regimen was better at achieving minimal residual disease negativity, meaning that a patient has no detectable myeloma cells. Bristol Myers Squibb (BMS), the company developing Zenbexus, previously announced that this goal had been met.

BMS now announced that EXCALIBER-RRMM also met its other main goal: to determine whether Zenbexus would improve progression-free survival, defined as the length of time patients remain alive and free from disease progression.

“The results from EXCALIBER-RRMM reinforce the clinical value of ZENBEXUS in combination with daratumumab and dexamethasone as a treatment approach for relapsed or refractory multiple myeloma, demonstrating the strong benefit observed for minimal residual disease negativity translated to a meaningful improvement in progression free survival for patients,” Cristian Massacesi, MD, chief medical officer and head of development at BMS, said in a company press release.

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According to BMS, median progression-free survival time among patients given Zenbexus was 42 months (3.5 years). By contrast, in patients given the Velcade regimen median progression-free survival time was 20 months (about 1.5 years). This works out to a 51% reduction in the risk of disease progression or death with Zenbexus.

BMS said it will present the top-line results at the American Society of Hematology annual meeting, to be held in December in New Orleans.

“These findings further underscore the value of ZENBEXUS as an effective oral treatment option that can be easily used in diverse care settings, including community settings, where many patients receive their care,” Massacesi said. “We look forward to sharing full results from the study.”

Zenbexus belongs to a class of next-generation immunomodulatory drugs called cereblon E3 ligase modulators, or CELMoDs, which work to kill myeloma cells by leveraging a protein, cereblon, to degrade key disease-causing proteins. The therapy was conditionally approved in the U.S. earlier this year based on initial data from EXCALIBER-RRMM showing that the Zenbexus regimen improved rates of minimum residual disease negativity.