Monthly etentamig significantly improved response and PFS over standard available therapies in the phase 3 CERVINO trial, with low rates of high-grade CRS.
Etentamig significantly improved overall response and progression-free survival (PFS) compared with investigator's choice of standard available therapies (SAT) in patients with triple-class exposed relapsed/refractory multiple myeloma, according to primary findings from the phase 3 CERVINO trial (NCT06158841) presented at the
At a median follow-up of 11.4 months (range, 0.5-24.3), the overall response rate (ORR) per independent review committee was 74.0% with etentamig (n = 196) vs 45.7% with SAT (n = 197), a difference of 28.3 percentage points (95% CI, 18.49-37.46; P < .0001). Rates of very good partial response or better were 63% vs 20%, and complete response (CR) or better rates were 40% vs 7%, respectively. The median PFS was not reached with etentamig vs 6.2 months with SAT (HR, 0.40; 95% CI, 0.29-0.54; P < .0001), and 12-month PFS rates were 62.1% vs 28.4%, respectively.
"Compared [with] other phase 3 studies evaluating bispecific antibodies, this is a more heavily pretreated population than what has been presented and published to date," said lead study author Peter M. Voorhees, MD, chief of the Plasma Cell Disorders Division at Atrium Health Levine Cancer Institute, Wake Forest University School of Medicine, in Charlotte, North Carolina.
The open-label, randomized trial enrolled patients with relapsed/refractory multiple myeloma who had received at least 2 prior lines of therapy, including exposure to a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 monoclonal antibody.1 Prior BCMA-directed therapy was not permitted. In total, 393 patients were randomly assigned 1:1 to etentamig or SAT, with stratification by number of prior lines of therapy, International Staging System stage, and region.
SAT consisted of carfilzomib (Kyprolis) plus dexamethasone (47.2%); selinexor (Xpovio), bortezomib (Velcade), and dexamethasone (17.8%); or elotuzumab (Empliciti), pomalidomide (Pomalyst), and dexamethasone (33.0%). Etentamig was administered at 60 mg every 4 weeks. After the study opened, a single 2-mg step-up dose on day 1 followed by the 60-mg full dose on day 4 was implemented on the basis of phase 1 dose-optimization data; 113 of the 195 treated patients in the etentamig arm received this regimen. Treatment could stop after at least 24 cycles in patients with a sustained CR or better lasting at least 12 months, and outpatient initiation was allowed.
ORR and PFS were the coprimary end points. Key secondary end points included OS, CR or better and very good partial response or better, minimal residual disease (MRD)–negative CR at 10-5, and patient-reported outcomes.
In the etentamig and SAT arms, 30.6% and 33.5% of patients, respectively, were at least 75 years of age, and 27.0% and 19.3% were treated at non-academic centers. The median number of prior lines of therapy was 3 in both arms, with 26.0% and 30.5% having received at least 4 prior lines. Overall, 89.3% and 90.9% were refractory to their last line of therapy, and 51.5% and 52.3% had triple-class refractory disease.
The PFS benefit was consistent across prespecified subgroups, including patients aged 75 years or older (HR, 0.27; 95% CI, 0.14-0.50) and those treated at non-academic centers (HR, 0.39; 95% CI, 0.20-0.75).
Among evaluable patients who achieved CR or better, MRD negativity at 10-5 was 89.1% with etentamig (n = 64) vs 25.0% with SAT (n = 8). The median duration of response was not reached with etentamig vs 10.2 months with SAT (HR, 0.31; 95% CI, 0.18-0.53), and 12-month duration of response rates were 79.8% vs 48.1%, respectively.
In the OS analysis, the median was not reached in either arm; the 12-month OS rates were 87.9% vs 72.0% (HR, 0.48; 95% CI, 0.29-0.77; nominal P = .0012), although the prespecified efficacy boundary for OS was not crossed at this analysis. Among SAT-treated patients who received post-study therapy, 75% went on to receive a T-cell engager or chimeric antigen receptor T-cell therapy. Nonrelapse mortality was 5.1% with etentamig vs 9.8% with SAT, and relapse mortality was 8.2% vs 15.0%, respectively.
Any-grade treatment-emergent adverse effects (TEAEs) occurred in 97.9% of patients in the etentamig arm (n = 195) and 95.3% of those in the SAT arm (n = 193); grade 3/4 TEAEs occurred in 70.8% and 59.6%, and grade 5 TEAEs in 2.6% and 5.7%, respectively. AEs were the primary reason for discontinuation in 3.6% vs 9.6% of patients.
The most common hematologic TEAE with etentamig was neutropenia (any grade, 46.7%; grade 3/4, 38.5%). Any-grade infections occurred in 69.7% of the etentamig arm vs 59.1% of the SAT arm; grade 3/4 infections occurred in 27.7% vs 19.2%, and grade 5 infections in 1.5% vs 3.1%. Opportunistic infections occurred in 3.6% of etentamig-treated patients. Grade 3 or higher infections were concentrated in the first 6 months of treatment with etentamig (22.6%) and declined to 8.0% in months 6 to 12 and 4.9% in months 12 to 18.
Across the full etentamig arm, CRS occurred in 39.5% of patients (grade 1, 27.2%; grade 2, 11.3%; grade 3, 1.0%). Among the 113 patients who received the single step-up dose, the CRS rate was 28.3% (grade 1, 23.9%; grade 2, 4.4%), with no grade 3 or higher events; no CRS occurred in the 22 patients who also received prophylactic tocilizumab (Actemra). In the single step-up dose group, the median time to CRS onset was 20.9 hours (range, 5.0-71.1), and the median time to resolution was 6.0 hours. Immune effector cell–associated neurotoxicity syndrome (ICANS) occurred in 3.6% of the overall etentamig arm and in 1 patient (0.9%; grade 1) in the single step-up dose group.
In the 53 etentamig-treated patients at non-academic centers, grade 3/4 infections occurred in 22.6%, and there were no grade 3 or higher CRS events and no ICANS. Across all treatment settings, 13% of etentamig-treated patients received primary immunoglobulin replacement therapy, 63% received secondary replacement, and 24% received none.
