Iberdomide

ZENBEXUS is indicated, in combination with daratumumab and hyaluronidase-fihj and dexamethasone, 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. 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). ZENBEXUS is a cereblon-modulating protein degrader indicated in combination with daratumumab and hyaluronidase-fihj and dexamethasone 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.

Iberdomide is a cereblon-modulating protein degrader that binds to cereblon, a substrate recognition component of an E3 ubiquitin ligase complex. Iberdomide engages cereblon and facilitates recruitment, ubiquitination, and proteasomal degradation of the transcription factors, Aiolos and Ikaros, resulting in anti‑tumor and immunomodulatory activity. In vitro and in vivo, iberdomide treatment showed anti-tumor activity in multiple myeloma (MM) cells and xenografts including in lenalidomide- and pomalidomide-resistant MM cell lines. Immunomodulatory properties of iberdomide include increased secretion of the immune stimulatory cytokines (interleukin-2 and interferon-gamma), inhibition of proinflammatory cytokine release (interleukin-6), enhanced immune mediated killing of MM cells, and prevention of T-cell exhaustion.

• Recommended dosage: 1 mg orally once daily with or without food on Days 1 to 21 of repeated 28-day cycles until disease progression or unacceptable toxicity. • See Full Prescribing Information for recommended ZENBEXUS dosage modifications.

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. Iberdomide causes adverse developmental outcomes in both rats and rabbits when administered during the period of organogenesis. 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. • Pregnancy (Boxed Warning, 4, 5.1, 8.1)

Boxed 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 [ Contraindications, see Warnings and Precautions and Use in Specific Populations ]. • Neutropenia: Monitor complete blood counts at baseline and throughout treatment. Interrupt, reduce, or discontinue ZENBEXUS and initiate growth factor support as appropriate. • Infections: Can cause severe, life-threatening, or fatal infections. Monitor patients for signs and symptoms of infection, including opportunistic infections, and treat appropriately.

The following clinically significant adverse reactions are described elsewhere in the labeling. • Serious Venous and Arterial Thromboembolism • Neutropenia • Infections • Second Primary Malignancies Most common (≥20%) adverse reactions with ZENBEXUS in combination with daratumumab and hyaluronidase-fihj and dexamethasone are upper respiratory tract infection, fatigue, musculoskeletal pain, pneumonia, diarrhea, motor dysfunction, rash, sleep disorder, hypogammaglobulinemia, COVID-19, and constipation. The most common Grade 3 or 4 (≥30%) laboratory abnormalities are neutrophil count decreased, white blood cell count decreased, and lymphocyte count decreased.

• Strong or moderate CYP3A inhibitors: Avoid concomitant use with ZENBEXUS or, if concomitant use is unavoidable, reduce dose. • Strong or moderate CYP3A inducers: Avoid concomitant use with ZENBEXUS.

Store at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C to 30°C (59°F to 86°F). Store and dispense in the original bottle with desiccant.