Alnuctamab, a bivalent B-cell maturation antigen-targeting T cell engager for patients with relapsed or refractory multiple myeloma: results from a phase 1, first-in-human study
Year: 2026
Type: article
Study design: Clinical Trial
Abstract: B-cell maturation antigen (BCMA)-targeting therapies provide a new approach to treating multiple myeloma (MM). Alnuctamab (ALNUC) is a 2 + 1 immunoglobulin G1-based bispecific antibody binding BCMA and CD3ε receptors on myeloma and T cells, respectively. CC-93269-MM-001 is a first-in-human, phase 1 dose escalation/expansion study investigating ALNUC in relapsed/refractory MM. Patients had ≥3 prior regimens, disease progression ≤60 days of last regimen, and were BCMA-directed therapy-naïve. ALNUC was administered intravenously (IV) and subcutaneously (SC); however, SC was selected for further evaluation due to the more favorable safety profile. Ninety-five patients received ALNUC SC; at data cutoff, 44.2% remained on treatment and median follow-up was 8.0 months. The recommended phase 2 dose was 30 mg. The most common treatment emergent adverse events (any grade/grade 3/4) were CRS (57.9%/0%), and neutropenia (53.7%/43.2%). Infections were also frequent (64.2%/14.7%). ORR was 58.9% for all ALNUC SC-treated patients and 71.4% for the 30-mg cohort; 47/95 (49.5%) were measurable residual disease (MRD) negative. Overall, the safety and efficacy of ALNUC SC were comparable to other BCMA-targeted therapies. These results support improved safety of SC versus IV, and corroborate a step-up dosing strategy to mitigate CRS. Importantly, a schedule that de-intensifies over time provides favorable toxicity that may be applicable to other bispecific engagers.
Source: Leukemia
Authors: Noffar Bar, Thomas Martin, Craig C. Hofmeister, Maria-Victoria Mateos, Markus Hansson, Laura Paris, Swathi Namburi, Paz Ribas, Armando Santoro, Paula Rodriguez-Otero, Maria Creignou, Jinjie Chen, Cong Cao, Brian Kiesel, Allison Gaudy, Ethan G. Thompson, Ye Shen, Samah Zarif, Kevin Hsu, Suresh G. Shelat, Michael R. Burgess, Colin Godwin, Luciano J. Costa
Institutions: Yale Cancer Center, Yale University, University of California, San Francisco, Winship Cancer Institute, Universidad de Salamanca, Instituto de Investigación Biomédica de Salamanca, Centro de Investigación del Cáncer, Instituto de Biología Molecular y Celular del Cáncer de Salamanca, Sahlgrenska University Hospital, Skåne University Hospital, Ospedale Papa Giovanni XXIII, Swedish Medical Center, Swedish Medical Center, Hospital Universitario Doctor Peset, Humanitas University, IRCCS Humanitas Research Hospital, Clinica Universidad de Navarra, Centro de Investigación Biomédica en Red de Cáncer, Centro de Investigación Médica Aplicada, Karolinska University Hospital, Bristol-Myers Squibb (United States), Bristol-Myers Squibb (Switzerland), University of Alabama at Birmingham
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $5,190
Funder: Bristol-Myers Squibb
OpenAlex ID: W7118530433