Bristol Myers Squibb has reported positive Phase 3 results for ZENBEXUS (iberdomide), with the drug combination delivering a statistically significant improvement in progression-free survival (PFS) among patients with relapsed multiple myeloma.

 

In the EXCALIBER-RRMM study involving 800 patients, ZENBEXUS combined with daratumumab and dexamethasone (ZDd) achieved a median progression-free survival of 42 months, compared with 20 months for the standard combination of daratumumab, bortezomib and dexamethasone (DVd).

 

The results translate into a 51% reduction in the risk of disease progression or death, with a hazard ratio of 0.49. Median follow-up was 23 months.

 

BMS said the safety profile of ZENBEXUS in combination with standard therapies was consistent with previously reported findings from the study.

 

The findings strengthen the clinical case for ZENBEXUS in relapsed or refractory multiple myeloma (RRMM), a blood cancer that remains incurable.

 

“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,” said Cristian Massacesi, chief medical officer and head of development at Bristol Myers Squibb.

 

“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. We look forward to sharing full results from the study.”

 

The latest results build on previously reported improvements in minimal residual disease (MRD)-negative complete response, the trial’s other dual-primary endpoint. Those findings supported the US Food and Drug Administration’s accelerated approval of ZENBEXUS for relapsed or refractory multiple myeloma.

 

The EXCALIBER-RRMM trial enrolled adults whose disease had progressed after one or two previous lines of anti-myeloma therapy. The 800 patients included in the confirmatory PFS analysis were randomized equally between the two treatment groups, with 400 patients receiving each regimen.

 

The study assessed MRD negativity and progression-free survival as its dual-primary endpoints. Secondary endpoints included overall survival, overall response rate, safety and sustained MRD negativity.

 

Despite the efficacy results, ZENBEXUS carries significant safety warnings, including risks of embryo-fetal toxicity and serious venous and arterial thromboembolic events.

 

The drug is contraindicated during pregnancy and is available only through the restricted ZENBEXUS REMS distribution programme because of the risk of fetal harm. The prescribing information also recommends antithrombotic prophylaxis to reduce the risk of blood clots and related complications.

 

Other important risks include severe neutropenia, serious infections and second primary malignancies. BMS advises monitoring patients throughout treatment and adjusting or interrupting therapy when clinically necessary.

 

The company’s prescribing information reports that serious adverse reactions occurred in 58.3% of patients receiving the ZENBEXUS combination in the relevant study population. Fatal adverse reactions occurred in 4.9% of patients in that treatment arm.

 

The efficacy findings therefore represent an important clinical development, but treatment decisions will need to account for the drug’s safety profile and individual patient risks.