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ZENBEXUS + Dd is the first RRMM treatment to receive accelerated approval based on MRD-negative CR1

Studied in patients generally representative of today’s 2L population

EXCALIBER-RRMM IS A PHASE 3, MULTICENTER, OPEN-LABEL STUDY IN PATIENTS WITH RRMM1

Inclusion Criteria: Adults with 1 to 2 prior lines of anti-myeloma therapy and progressive disease. Exclusion Criteria: Refractory to bortezomib or an anti-CD38 therapy. Randomization 1:1 (n=664). ZDd (n=332)*. Regimens in each arm were given until disease progression or unacceptable toxicity. DVd (n=332)†

Dual primary endpoints2:

  • MRD-negative ≥CR at any time‡
  • PFS

Key secondary endpoints2:

  • OS
  • ORR§
  • Safety
  • Sustained
    MRD
    negativity

Select baseline characteristics1,3:

90% were exposed to an IMiD (n=379/420)

22% had high-risk cytogenetics (n=92/420)∥

18% ≥75 years of age (n=76/420)

*ZENBEXUS 1 mg was administered orally on Days 1-21. Daratumumab and hyaluronidase-fihj 1800 mg (subcutaneous) was administered in Cycles 1-2 on Days 1, 8, 15, and 22; in Cycles 3-6 on Days 1 and 15; in Cycles 7+ on Day 1. Dexamethasone 20 or 40 mg was administered orally on Days 1, 8, 15, and 22. Dosing in the ZENBEXUS + Dd arm was in 28-day cycles.1
†Daratumumab and hyaluronidase-fihj 1800 mg subcutaneous was administered in Cycles 1-3 on Days 1, 8, and 15; in Cycles 4-8 on Day 1; in Cycles 9+ on Day 1. Bortezomib 1.3 mg/m2 (subcutaneous) was administered in Cycles 1-8 only on Days 1, 4, 8, and 11. Dexamethasone 10 or 20 mg was administered orally in Cycles 1-8 only on Days 1, 2, 4, 5, 8, 9, 11, and 12. For the DVd arm, dosing was in 21-day cycles for Cycles 1-8 and 28-day cycles for Cycle 9 onwards.2
‡Based on a threshold of 10-5 using a Hematogenix Next Generation Flow Cytometry assay.1
§Response was based on Independent Review Committee (IRC) assessment per International Myeloma Working Group (IMWG) 2016 criteria.1
∥Presence of del(17p), t(4;14), or t(14;16).1

2L=second line; APP=advanced practice provider; CR=complete response; Dd=daratumumab and hyaluronidase-fihj and dexamethasone; DVd=daratumumab and hyaluronidase-fihj, bortezomib, and dexamethasone; ECOG=Eastern Cooperative Oncology Group; IMiD=immunomodulatory drug; ISS=International Staging System; MM=multiple myeloma; MOA=mechanism of action; MRD=minimal residual disease; ORR=overall response rate; OS=overall survival; PFS=progression-free survival; RRMM=relapsed/refractory multiple myeloma; SCT=stem cell transplant; ZDd=ZENBEXUS, daratumumab and hyaluronidase-fihj, and dexamethasone.

Baseline characteristics3

CATEGORY ZENBEXUS + Dd
(N=207)
n (%)		 DVd
(N=213)
n (%)
Age Categorization    
≤64 80 (39) 80 (38)
65–74 88 (43) 96 (45)
≥75 39 (19) 37 (17)
Race    
White 122 (59) 135 (63)
Black or African American 2 (1.0) 2 (0.9)
Asian 77 (37) 72 (34)
Not known 6 (2.9) 4 (1.9)
Sex    
Male 117 (57) 127 (60)
Female 90 (43) 86 (40)
ISS Stage at Study Entry    
Stage I 124 (60) 141 (66)
Stage II 59 (29) 44 (21)
Stage III 24 (12) 28 (13)
Cytogenetics Abnormality    
High-risk 48 (23) 44 (21)
Presence of Extramedullary Plasmacytomas    
Yes 23 (11) 24 (11)
No 184 (89) 189 (89)
Baseline ECOG Performance Status    
0 116 (56) 132 (62)
1 82 (40) 78 (37)
2 9 (4.3) 3 (1.4)
Prior SCT    
Yes 142 (69) 141 (66)
No 65 (31) 72 (34)
Number of Prior Anti-myeloma Lines of Therapy    
1 139 (67) 143 (67)
2 68 (33) 70 (33)
Previous IMiD Exposure    
Previous lenalidomide exposure 142 (69) 150 (70)
Refractory to IMiD 105 (51) 97 (46)
Previous Anti-CD38 Exposure    
Yes 11 (5.3) 5 (2.3)
No 196 (95) 208 (98)
Previous PI Exposure 195 (94) 202 (95)
Previous Exposure to PI and IMiD 177 (86) 182 (85)

Dd=daratumumab and hyaluronidase-fihj and dexamethasone; DVd=daratumumab and hyaluronidase-fihj, bortezomib, and dexamethasone; ECOG=Eastern Cooperative Oncology Group; IMiD=immunomodulatory drug; ISS=International Staging System; MM=multiple myeloma; PI=proteasome inhibitor; RRMM=relapsed/refractory multiple myeloma; SCT=stem cell transplant.

The efficacy of ZDd was established in the EXCALIBER-RRMM study

References: 1. ZENBEXUS [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; 2026. 2. Lonial S, Dimopoulos MA, Berdeja JG, et al. Future Oncol. 2025;21(14):1761-1769. doi: 10.1080/14796694.2025.2501920 3. Data on file. BMS-REF-00030-2070. Princeton, NJ: Bristol-Myers Squibb Company; 2026.

References

IMPORTANT SAFETY
INFORMATION

WARNING: EMBRYO-FETAL TOXICITY AND SERIOUS VENOUS AND ARTERIAL THROMBOEMBOLISM

EMBRYO-FETAL TOXICITY

ZENBEXUS is contraindicated in pregnancy. ZENBEXUS is embryo-fetal toxic in animals and can cause birth defects or embryo-fetal death in humans. In females of reproductive potential, obtain 2 negative pregnancy tests before starting ZENBEXUS treatment.

Females of reproductive potential must use 2 effective forms of contraception or continuously abstain from heterosexual sex during and for 4 weeks after last dose of ZENBEXUS treatment.

Because of the risk of embryo-fetal toxicity, ZENBEXUS is only available through a restricted distribution program called ZENBEXUS REMS.

SERIOUS VENOUS AND ARTERIAL THROMBOEMBOLISM

Increased risk of deep vein thrombosis (DVT), pulmonary embolism (PE), myocardial infarction, and stroke in patients with multiple myeloma receiving ZENBEXUS with daratumumab and hyaluronidase-fihj and dexamethasone. Anti-thrombotic prophylaxis is recommended.

CONTRAINDICATIONS

Based on the mechanism of action and findings in animal studies, ZENBEXUS can cause birth defects or embryo-fetal death in humans. ZENBEXUS is contraindicated in females who are pregnant. If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be informed of the potential hazard to a fetus.

WARNINGS AND PRECAUTIONS

Embryo-Fetal Toxicity

Females of Reproductive Potential: Must avoid pregnancy while taking ZENBEXUS and for at least 4 weeks after completing therapy. Advise females of reproductive potential of the potential risk to a fetus and to use 2 methods of effective contraception for at least 4 weeks before beginning ZENBEXUS therapy, during therapy, during dose interruptions and for at least 4 weeks after the last dose of ZENBEXUS therapy. Refer patients who can become pregnant to a qualified provider of contraceptive methods, if needed.

Two negative pregnancy tests with a sensitivity of at least 25 mIU/mL must be obtained prior to initiating therapy. Pregnancy testing should be performed weekly during the first 4 weeks of treatment. Thereafter, testing should occur every 4 weeks in patients with regular menstrual cycles, or every 2 weeks in patients with irregular menstrual cycles.

Females of reproductive potential taking ZENBEXUS must not donate eggs during treatment and for 4 weeks after completion.

Males: ZENBEXUS may pass into human semen. Advise patients who can impregnate partners to use effective contraception during treatment and for 4 weeks following the discontinuation of ZENBEXUS therapy. Male patients taking ZENBEXUS must not donate sperm during treatment and for 4 weeks after completion.

Blood Donation: Patients must not donate blood during treatment with ZENBEXUS and for 4 weeks following discontinuation of ZENBEXUS therapy.

ZENBEXUS REMS

ZENBEXUS is available only through a restricted program called ZENBEXUS REMS, because of the risk of embryo-fetal toxicity. Prescribers must be certified with, and patients must be enrolled in the ZENBEXUS REMS Program and comply with ongoing monitoring and contraception requirements. Further information about ZENBEXUS REMS, including information for pharmacies, wholesalers, and distributors, is available at www.ZENBEXUSREMS.com or by telephone at 1-888-423-5436.

Serious Venous and Arterial Thromboembolism

ZENBEXUS can cause serious and life-threatening venous thromboembolic events (DVT and PE) and arterial thromboembolic events (myocardial infarction and stroke). In the EXCALIBER-RRMM study (N=204), venous thromboembolic events occurred in 6.4% of patients treated with ZENBEXUS combined with daratumumab and hyaluronidase-fihj and dexamethasone (IberDd) despite mandatory thromboembolism prophylaxis. The incidence of DVT was 3.4% and the incidence of PE was 1.5%.

Arterial thromboembolic events occurred in 3.4% of patients. The incidence of myocardial infarction was 2.0%, and the incidence of stroke (CVA) was 1.5%.

Monitor patients for signs and symptoms of thromboembolic events during treatment with ZENBEXUS. Patients with known risk factors, including prior thrombosis, may be at greater risk, and actions should be taken to try to minimize all modifiable factors (e.g., hyperlipidemia, hypertension, smoking). Thromboprophylaxis is recommended, and the choice of regimen should be based on assessment of the patient's underlying risk factors. In patients who develop a thromboembolism, interrupt ZENBEXUS and initiate anticoagulant therapy according to guidelines.

Neutropenia

ZENBEXUS can cause severe neutropenia. In the EXCALIBER-RRMM study, all-grade neutropenia was reported in 90.2%, Grade 3 in 30.9%, and Grade 4 in 53.4% of patients in the IberDd arm. Febrile neutropenia occurred in 5.4% of patients.

Monitor complete blood count throughout treatment with ZENBEXUS. Interrupt, reduce dosage, or discontinue ZENBEXUS, as necessary. Initiate granulocyte colony-stimulating factor (GCSF) as appropriate per guidelines.

Infections

ZENBEXUS can cause serious infections, including life-threatening or fatal infections. Patients with active or uncontrolled infection should not start ZENBEXUS treatment until the infection is controlled. In the EXCALIBER-RRMM study, infections, including opportunistic infections, were reported in 78.9%, Grade 3 in 35.8%, Grade 4 in 3.4%, and fatal infections in 2% of patients receiving IberDd. Serious infections occurred in 40% of patients. Discontinuations due to infections occurred in 1.5% of patients.

Monitor patients for signs and symptoms of infection prior to and during treatment with ZENBEXUS and treat appropriately. Withhold or reduce the dose based on severity.

Consider prophylactic anti-infective medications according to current practice guidelines.

Second Primary Malignancies

In the EXCALIBER-RRMM study, at a median follow-up time of 16 months, second primary malignancies (SPM) occurred in 6.9% of patients in the IberDd arm and 4.9% of patients in the daratumumab and hyaluronidase-fihj, bortezomib, and dexamethasone (DVd) arm.

Monitor patients for the development of SPM.

ADVERSE REACTIONS

Serious adverse reactions occurred in 58.3% of patients receiving ZENBEXUS. Serious adverse reactions in ≥2% of patients included pneumonia (26%), upper respiratory tract infection (6.4%), SPM (5.9%), neutropenia (4.9%), febrile neutropenia (3.9%), COVID-19 (4.4%), and sepsis (2.9%). Fatal adverse reactions 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 adverse reactions occurred in 1 patient each: listeria encephalitis, influenza, lung adenocarcinoma, cardiac arrest, large intestine perforation, metabolic acidosis, and respiratory failure.

The most common adverse reactions (≥20%) in the IberDd 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%).

The most common Grade 3 to 4 laboratory abnormalities (≥30%) in the IberDd arm and DVd arm, respectively, were neutropenia (77% and 11%), leukopenia (69% and 18%), and lymphopenia (62% and 51%).

DRUG INTERACTIONS

Effects of Other Drugs on ZENBEXUS

Strong or Moderate CYP3A Inhibitors: Coadministration of ZENBEXUS with strong or moderate CYP3A inhibitors should be avoided. If a strong or moderate CYP3A inhibitor must be used in combination with ZENBEXUS, reduce the ZENBEXUS dose. Concomitant use with strong or moderate CYP3A inhibitors may increase the risk of adverse reactions.

Strong or Moderate CYP3A Inducers: Coadministration of ZENBEXUS with strong or moderate CYP3A inducers should be avoided. Concomitant use with a strong or moderate CYP3A inducer may decrease the efficacy of ZENBEXUS.

SPECIFIC POPULATIONS

Pregnancy (See Boxed WARNINGS)

There is a pregnancy exposure registry that monitors outcomes in patients exposed to ZENBEXUS during pregnancy. See the ZENBEXUS REMS WARNINGS AND PRECAUTIONS section.

Lactation

Advise women not to breastfeed during treatment with ZENBEXUS. Refer to the Prescribing Information for daratumumab and hyaluronidase-fihj or dexamethasone for additional information.

Females and Males of Reproductive Potential

ZENBEXUS can cause fetal harm when administered during pregnancy.

Pregnancy Testing, Females of Reproductive Potential, and Males: See the Embryo-Fetal Toxicity WARNINGS AND PRECAUTIONS section.

Geriatric Use

In patients treated with IberDd, the incidence of serious adverse reactions was 53%, 56%, and 74% in adult patients younger than 65 years of age, 65 years of age to younger than 75 years of age, and 75 years of age and older, respectively.

Renal Impairment

Reduce the ZENBEXUS dose in patients with estimated glomerular filtration rate (eGFR) less than 30 mL/min/1.73 m2 not on dialysis. If dose modification is needed due to adverse events, reduce the ZENBEXUS dose to 1 mg every other day on Days 1 to 21 of a 28-day cycle.

Please see full Prescribing Information for ZENBEXUS including Boxed WARNINGS.

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ZENBEXUS and its associated logo are trademarks of Celgene Corporation, a Bristol Myers Squibb company.
All other trademarks are the property of their respective owners.

© 2026 Bristol-Myers Squibb Company.

2070-US-2600011  08/26