With the FDA approval of Zenbexus this summer, Bristol Myers Squibb checked off two notable ‘firsts,’ scoring the inaugural FDA green light for a CELMoD therapy and the first for a new drug in multiple myeloma that hinged on minimal residual disease as a surrogate endpoint, rather than traditional long-term metrics of oncology efficacy like progression-free survival.
Now, BMS has put up the PFS numbers on the Zenbexus (iberdomide) regimen as well, more than doubling the score over a control cocktail of daratumumab, bortezomib and dexamethasone (DVd).
The data round out the clinical picture on Zenbexus, which picked up an accelerated approval in August as part of a combination regimen with Johnson & Johnson’s Darzalex (daratumumab) and dexamethasone in adults with multiple myeloma who’ve received at least one prior line of therapy.
The approval notably leveraged minimal residual disease (MRD) data on the BMS cocktail—one of two dual primary endpoints—which tied the Zenbexus regimen to an MRD-negative complete response rate of 41%, versus 21% on the control regimen at any time during a median follow-up of 16 months.
In new results from the late-stage Excaliber-RRMM study posted Thursday, BMS further tied its Zenbexus combo to a median PFS of 42 months, compared to 20 months on the traditional multiple myeloma regimen of Darzalex, Velcade and dexamethasone. That translates to a 51% reduction in the risk of disease progression or death in Zenbexus’ favor, the company said in an Oct. 8 release.
Given the accelerated status of the drug’s August approval, BMS is on the hook to provide confirmatory evidence on Zenbexus, which this week’s PFS win could contribute to.
Indeed, the new data “reinforce the clinical value” of the Zenbexus regimen in relapsed or refractory multiple myeloma, said BMS' chief medical officer and development head, Cristian Massacesi, M.D., in a statement.
The readout should validate the premise that underpinned the approval—that the “strong benefit observed for minimal residual disease negativity translated to a meaningful improvement in progression-free survival for patients,” he added.
BMS is planning to share further details from its Excaliber-RRMM trial at the annual meeting of the American Society of Hematology in New Orleans in December.
With Zenbexus’ approval, BMS took a major leap forward in validating protein degradation—and its CELMoD agents specifically—as a viable modality, as well as the worth of MRD as a future clinical benchmark.
BMS is currently awaiting an FDA decision on its second CELMoD asset, mezigdomide, in second-line-plus multiple myeloma, with a current decision target slated for mid-May of next year.