P-013: CERVINO: A phase 3, multicenter, randomized, open-label study of ABBV-383 compared with standard available therapies in patients with relapsed or refractory multiple myeloma (RRMM)

Introduction: Trial in progress. RRMM has a poor prognosis, and patients have limited treatment options after progression on available therapies including immunomodulatory drugs (IMiDs), proteasome inhibitors (PIs), and anti-CD38 mAbs. B-cell maturation antigen (BCMA) has been validated as a target for RRMM, and several BCMA-directed therapies have been approved. However, more tolerable, efficacious, and convenient BCMA-targeted therapies are needed to improve outcomes. The distinctive BCMA × CD3 bispecific antibody ABBV-383 is composed of 2 high-affinity BCMA-binding domains, a low-affinity CD3-binding domain designed to reduce the risk for cytokine release syndrome (CRS), and a silenced Fc tail resulting in an extended half-life that supports Q4W dosing. Encouraging efficacy and a manageable safety profile were seen in the first-in-human phase 1 trial with ABBV-383 in heavily pretreated patients with RRMM (Rodriguez et al. J Clin Oncol. 42, 2024;suppl 16:7531). The primary objective of this trial is to evaluate the efficacy, safety, and tolerability of ABBV-383 monotherapy compared with standard available therapies (SATs) in patients with RRMM following ≥2 prior therapies.

Methods: This global, phase 3, multicenter, randomized, open-label, parallel-group study (NCT06158841) enrolls patients (≥18 years) with RRMM and an ECOG performance status ≤2 who received ≥2 prior lines of therapy, including exposure to a PI, IMiD, and anti-CD38 mAb. Patients who received prior BCMA-targeted therapy are excluded. Patients are randomized 1:1 to receive IV ABBV-383 60 mg Q4W without step-up dosing or investigator’s choice of SAT (carfilzomib + dexamethasone, elotuzumab + pomalidomide + dexamethasone, or selinexor + bortezomib + dexamethasone), and will continue treatment until confirmed progressive disease or other discontinuation criteria are met.

ABBV-383 may be administered in an outpatient setting at sites with institutional guidelines. Otherwise, patients are admitted to hospital for ≥24 hrs on cycle 1 day 1 to monitor for CRS. In select countries, wearable digital health devices are used to collect vital sign data to characterize the CRS profile; these may include axillary temperature, cardiac and respiratory vital signs, and physical activity.

The dual primary end points are progression-free survival and overall response rate. Secondary end points include overall survival, complete response (CR), very good partial response or better, minimum residual disease negativity with ≥CR rates, and change in disease symptoms and physical functioning. Biospecimens are collected at different time points to assess PK and evaluate biomarkers. Approximately 140 sites total across Australia, Austria, Belgium, Canada, China, Czechia, Denmark, France, Germany, Greece, Hungary, Israel, Italy, Japan, Poland, Portugal, South Africa, South Korea, Spain, Sweden, Taiwan, Turkey, UK, and USA will enroll ~380 total patients.

Results: n/a

Conclusions: n/a