Correlative biomarker analyses for optimal therapeutic dose determination of ABBV-383, a B-cell maturation antigen (BCMA) x CD3 bispecific antibody, in patients with relapsed/refractory multiple myeloma (RRMM).
Year: 2024
Type: conference-abstract
Abstract: 7532 Background: ABBV-383 is a BCMA x CD3 bispecific antibody with 2 high-affinity BCMA-binding domains and a low-affinity CD3 engaging arm that has been shown to decrease the negative impact of soluble BCMA (sBCMA) and drive sustained T-cell activation with reduced cytokine release in preclinical models of MM. Here, we describe correlative biomarker results of baseline and longitudinal sBCMA levels and immune profiles in the ongoing first-in-human trial that supports 60 mg Q4W as the optimal therapeutic dose of ABBV-383 monotherapy. Methods: Peripheral blood and serum samples from patients with RRMM enrolled in the phase 1 open-label, dose-expansion study (NCT03933735) who received ABBV-383 at 20, 40, or 60 mg Q3W or 60 mg Q4W were collected at baseline (post-dexamethasone, pre–ABBV-383), on treatment, and at disease progression. Samples were analyzed by flow cytometry for immune cell populations, Luminex for cytokines, and electrochemiluminescence ligand binding for sBCMA. Results: Median sBCMA levels at baseline were highly variable among patients, but did not associate with clinical response (≥ partial response [PR]) to ABBV-383 at the selected optimal dose level of 60 mg Q4W ( min at cycle 5: max within cycle 1: 29, 349.5, 1375, 456.5 pg/mL, respectively), and promoted T-cell redistribution (89% reduction of CD8+ T cells from periphery), activation (1.9-fold increase in CD69+CD8+ T cells), and proliferation (2-fold increase in Ki67+CD8+ T cells) within cycle 1 in 60-mg Q4W-treated patients. The frequency of baseline CD8+ T-cell exhaustion (PD-1/TIM3) did not impact clinical response at the optimal dose level of 60 mg Q4W ABBV-383 (
Source: Journal of Clinical Oncology
Authors: Aarif Ahsan, Christine Mantis, Xizhi (Adam) Luo, Catherine C. Zhang, Cesar Rodriguez Valdes, Peter M. Voorhees, Anita D'Souza, Alfred Chung, Sascha Tuchman, Hana Safah, John T. McKay, Katja C Weisel, Raphael Teipel, Neha Korde, Ravi Vij, Shaji Kumar, Orlando Felix Bueno, Rajvineeth Kumar Pothacamury, Chetasi Talati, Jeremy A. Ross
Institutions: AbbVie (United States), Mount Sinai Hospital, Levine Cancer Institute, Wake Forest University, Froedtert Hospital, Medical College of Wisconsin Cancer Center, University of California, San Francisco, University of North Carolina at Chapel Hill, Tulane University, Wake Forest University Health Sciences, University Medical Center Hamburg-Eppendorf, University Hospital Carl Gustav Carus, Memorial Sloan Kettering Cancer Center, Washington University in St. Louis, Mayo Clinic
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4399480686