FDA granted accelerated approval to iberdomide (Zenbexus) in combination with daratumumab and hyaluronidase-fihj and dexamethasone for adults with multiple myeloma who have received at least one prior line of therapy including a proteasome inhibitor and an immunomodulatory agent.
Iberdomide is sponsored by Bristol-Myers Squibb Company. Full prescribing information for iberdomide will be posted on Drugs@FDA.
Efficacy was evaluated in EXCALIBER-RRMM (NCT04975997), a two-stage, randomized, multicenter, open-label trial in adults with relapsed or refractory multiple myeloma (RRMM) who had previously received one or two prior lines of therapy. Patients who had disease refractory to prior anti-CD38 monoclonal antibody therapy, or to prior bortezomib were excluded.
A total of 939 patients were randomized to one of three dose levels of iberdomide in combination with daratumumab and hyaluronidase-fihj and dexamethasone (IberDd) or to daratumumab and hyaluronidase-fihj, bortezomib and dexamethasone (DVd) in stage 1 (n=279); or to iberdomide 1 mg in combination with daratumumab and hyaluronidase-fihj and dexamethasone (Dd) or DVd in stage 2 (n=660).
The major efficacy outcome measure was minimal residual disease (MRD)-negative complete response (CR) at any time. The primary efficacy population included the first 420 patients randomized to iberdomide 1 mg in combination with Dd (n=207) or the comparator DVd arm (n=213) across stages 1 and stage 2. The MRD- negative CR rate at any time was 41% (95% CI: 34, 48) in the IberDd arm and 21% (95% CI: 15, 27) in the DVd arm (p-value <0.0001).
The prescribing information includes a boxed warning for embryo-fetal toxicity and serious venous and arterial thromboembolism, as well as warnings and precautions for neutropenia, infections, and secondary primary malignancies. Because of the risk of embryo-fetal toxicity, iberdomide is available only through a restricted distribution program called ZENBEXUS Risk Evaluation and Mitigation Strategy.
This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, FDA collaborated with Switzerland’s Swissmedic.
