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ZENBEXUS in combination with daratumumab and hyaluronidase-fihj and dexamethasone is indicated for the treatment of adult patients with multiple myeloma who have received at least 1 prior line of therapy including a proteasome inhibitor and an immunomodulatory agent.¹

This indication is approved under accelerated approval based on minimal residual disease (MRD)-negative complete response (CR) at any time. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).¹

Download the ZENBEXUS Prescribing Information to learn more.

ZENBEXUS is a transformational next-generation IMiD, belonging to a new class of CELMoDs.^1,2

ZENBEXUS is a cereblon-modulating protein degrader that binds to cereblon, a substrate recognition component of an E3 ubiquitin ligase complex.¹

In vitro and in vivo, ZENBEXUS treatment showed anti-tumor activity in multiple myeloma (MM) cells and xenografts including in lenalidomide- and pomalidomide-resistant MM cell lines.¹

New class=cereblon-modulating protein degrader; IMiD=immunomodulatory drug; MM=multiple myeloma.

The efficacy and safety of ZENBEXUS + Dd were evaluated in EXCALIBER-RRMM, a phase 3, two-stage, randomized, multicenter, open-label study in patients with RRMM.¹

A total of 939 patients were randomized. Data reported are based on the primary efficacy population for MRD negativity, which included the first 420 patients randomized to the ZENBEXUS (1 mg) + Dd arm (N=207) or the comparator daratumumab and hyaluronidase-fihj, bortezomib, and dexamethasone (DVd) arm (N=213). Treatment in both arms was administered until disease progression or unacceptable toxicity.¹

The dual primary endpoints of ZENBEXUS + Dd compared to DVd were minimal residual disease (MRD)-negative complete response (CR) at any time and progression-free survival. Key secondary endpoints included OS, ORR, safety, and sustained MRD negativity.³

Dd=daratumumab and hyaluronidase-fihj and dexamethasone; RRMM=relapsed/refractory multiple myeloma; OS=overall survival; ORR=overall response rate.

In a phase 3 trial, ZENBEXUS + Dd delivered approximately double the MRD-negative ≥CR rates vs DVd (41% vs 21%, p<0.0001).¹

Data reported on this page are based on the primary efficacy population for MRD negativity, which included the first 420 patients randomized to ZENBEXUS + Dd 1 mg arm (n=207) or the comparator DVd arm (n=213).¹

CR=complete response; Dd=daratumumab and hyaluronidase-fihj and dexamethasone; DVd=daratumumab and hyaluronidase-fihj, bortezomib, and dexamethasone; MRD=minimal residual disease.

In patients refractory to lenalidomide in the immediate prior line, ZENBEXUS + Dd showed consistent efficacy. 41% of patients achieved MRD-negative ≥CR rates in the overall population (n=85/207) compared to 37% of patients refractory to lenalidomide in the immediate prior line (n=33/90).^1,4

24% (n=20/83) of patients who were refractory to lenalidomide in the immediate prior line achieved MRD-negative ≥CR after receiving DVd.⁴

Limitations: This exploratory analysis was not powered to detect differences in treatment effect. No statistical testing was planned for this analysis; therefore, definitive conclusions should not be drawn.

Response was based on Independent Review Committee (IRC) assessment per International Myeloma Working Group (IMWG) 2016 criteria.¹

CR=complete response; Dd=daratumumab and hyaluronidase-fihj and dexamethasone; DVd=daratumumab and hyaluronidase-fihj, bortezomib, and dexamethasone; MRD=minimal residual disease.

ZENBEXUS has a familiar safety profile with few discontinuations (7.8%) due to ARs.^1,5,6 The most frequent AR which resulted in permanent ZENBEXUS discontinuation was neutropenia (1%).¹

Fatal ARs occurred in 10 patients (4.9%) who received ZENBEXUS. Sepsis (1.5%) was the only fatal drug reaction that occurred in more than 1 patient. The following fatal ARs occurred in 1 patient each: listeria encephalitis, influenza, lung adenocarcinoma, cardiac arrest, large intestine perforation, metabolic acidosis, and respiratory failure.¹

Serious ARs occurred in 58.3% of patients receiving ZENBEXUS. Serious ARs in ≥2% of patients included pneumonia (26%), upper respiratory tract infection (6.4%), second primary malignancy (5.9%), neutropenia (4.9%), febrile neutropenia (3.9%), COVID-19 (4.4%), and sepsis (2.9%)¹

The most common ARs (≥20%) in the ZDd arm and DVd arm, respectively, were upper respiratory tract infection (54% and 52%), fatigue (36% and 33%), musculoskeletal pain (35% and 33%), pneumonia (34% and 17%), diarrhea (33% and 36%), motor dysfunction (26% and 17%), rash (26% and 15%), sleep disorder (25% and 28%), hypogammaglobulinemia (24% and 12%), COVID-19 (23% and 16%), and constipation (20% and 22%).¹

AR=adverse reaction; COVID-19=coronavirus disease 2019; Dd=daratumumab and hyaluronidase-fihj and dexamethasone; DVd=daratumumab and hyaluronidase-fihj, bortezomib, and dexamethasone; ZDd=ZENBEXUS, daratumumab and hyaluronidase-fihj, and dexamethasone.

ZENBEXUS is an oral 1 mg pill with the same starting dose for most* patients. ZENBEXUS is given until disease progression or unacceptable toxicity. ZENBEXUS is given in combination with standard dosages of subcutaneous daratumumab and hyaluronidase-fihj and oral dexamethasone.¹

Avoid concomitant use of strong or moderate CYP3A inhibitors with ZENBEXUS.¹

If concomitant use with strong CYP3A inhibitors is unavoidable, reduce ZENBEXUS dose to 1 mg every other day on Days 1 to 21 of a 28-day cycle.¹

If concomitant use with moderate CYP3A inhibitors is unavoidable, reduce ZENBEXUS dose to 0.75 mg once daily on Days 1 to 21 of a 28-day cycle. If dose modification is needed due to adverse events, reduce ZENBEXUS dose to 1 mg every other day on Days 1 to 21 of a 28-day cycle.¹

Avoid concomitant use of strong or moderate CYP3A inducers with ZENBEXUS.¹

In patients with eGFR less than 30 mL/min/1.73 m² not receiving dialysis, reduce ZENBEXUS dose to 0.75 mg once daily on Days 1 to 21 of a 28-day cycle. If dose modification is needed due to adverse events, reduce ZENBEXUS dose to 1 mg every other day on Days 1 to 21 of a 28-day cycle.¹

In patients with eGFR greater than 30 mL/min/1.73 m² or eGFR less than 30 mL/min/1.73 m² receiving intermittent hemodialysis, no dose adjustment is recommended.¹

Dose adjustments may be required based on ARs (neutropenia, febrile neutropenia, thrombocytopenia [including with bleeding or requiring platelet transfusion], thromboembolism, and other ZENBEXUS-related ARs).¹

*Additional dose modifications may be needed for patients on strong or moderate CYP3A inhibitors and those with renal impairment. Preinitiation pregnancy testing may be required for some patients.¹

AR=adverse reaction; eGFR=estimated glomerular filtration rate.

BMS Access Support is dedicated to helping patients access their prescribed BMS medications. We may offer benefits investigations, prior authorization assistance, appeals process support, and information on financial support options. The BMS Access Support Co-Pay Assistance Program assists with out-of-pocket co-payment or co-insurance requirements for eligible, commercially insured patients who have been prescribed certain BMS products, including ZENBEXUS. For more information, visit www.BMSAccessSupport.com, or call BMS Access Support at 1-800-861-0048, 8 AM to 8 PM ET, Monday to Friday.