Data from <i>Ex Vivo</i> Efficacy of SAR442257 Anti-CD38 Trispecific T-cell Engager in Multiple Myeloma Relapsed After Daratumumab and BCMA-targeted Therapies

• DOI: 10.1158/2767-9764.c.7117113.v1
• Publication Date: 2024-03-12T19:24:12Z
• Authors: Alana L. Keller; Lauren T. Reiman; Olivia Perez de Acha; Sarah E. Parzych; Peter A. Forsberg; Peter S. Kim; Kamlesh Bisht; Hongfang Wang; Helgi van de Velde; Daniel W. Sherbenou
• Keywords: Daratumumab; Ex vivo

&lt;div&gt;Abstract&lt;p&gt;T cell–engaging antibodies (TCEs) are showing promising efficacy in relapsed/refractory multiple myeloma, even patients that relapsed after B-cell maturation antigen (BCMA)-targeted therapy. Patients with myeloma may have compromised T-cell health unaccounted for by preclinical models. Here, we use Myeloma Drug Sensitivity Testing (My-DST) &lt;i&gt;ex vivo&lt;/i&gt; measurement of anti-multiple cytotoxicity the trispecific CD38/CD28xCD3 TCE SAR442257 through activation patients’ own endogenous T cells to inform clinical development compound myeloma. My-DST incubates primary mononuclear humanized media 48 hours followed flow cytometry cell viability or without drug treatment. was tested on 34 samples from across disease settings. Potential biomarkers, dependence, and degranulation were assessed. effective at low dose cultures. High response rates observed aspirates taken diagnosis, modestly reduced recently treated anti-CD38 mAbs. highly relapsing BCMA The format substantially more than a conventional bispecific CD38/CD3 antibody CD38 Anti-multiple dependent presence cells. Surface expression strongest biomarker response. is capable measuring cell–dependent killing using patient's bone marrow–derived shows promise be best suited declared resistant both mAbs BCMA-targeted therapy.&lt;/p&gt;Significance:&lt;p&gt;This study introduces measure characterize sensitivity engager matched Preclinical testing diverse treatment history supports further post-chimeric receptor myeloma.&lt;/p&gt;&lt;/div&gt;