P937: PRECLINICAL DISCOVERY AND EARLY FINDINGS FROM THE PHASE 1, DOSE-ESCALATION STUDY OF WVT078, A BCMA-CD3 BISPECIFIC ANTIBODY, IN PATIENTS WITH R/R MULTIPLE MYELOMA

• DOI: 10.1097/01.hs9.0000846616.21003.5d
• Publication Date: 2022-06-23T17:00:13Z
• Authors: M. S. Raab; Y. C. Cohen; F. Schjesvold; K. Aardalen; A. Oka; A. Spencer; M. Wermke; P. Hari; J. L. Kaufman; A. M. Cafro; E. M. Ocio; N. Doki; K. Henson; G. Trabucco; P.-E. Juif; R. Chawla; J. Cotton; A. Fessehatsion; L. Fan; J. Blankenship; B. Granda; H. Lu; S. De Vita
• Keywords: Tolerability; Bispecific antibody

Background: B-cell maturation antigen (BCMA) is a member of the tumor necrosis factor receptor superfamily with selective expression on benign and malignant plasma cells. Signaling through BCMA mediates survival proliferation multiple myeloma (MM) validated clinical target BCMA-directed therapies approved or in development for patients relapsed and/or refractory (r/r) MM. Bispecific antibodies (BsAbs) offer convenient alternative to chimeric receptor–modified T-cell (CAR-T) targeting are demonstrating high response rates Here we describe discovery WVT078, novel BCMA-CD3 BsAb report initial data from ongoing phase 1 study (NCT04123418) evaluating ascending doses WVT078 r/r Aims: To evaluate safety tolerability Methods: Multiple candidates were characterized vitro vivo T cell activation anti-MM activity. The activity prioritized further assessed an integrated pharmacology cynomolgus monkeys. was selected being tested MM who ≥2 standard care regimens including immunomodulatory drug, proteasome inhibitor, anti-CD38 agent (if available). Patients have received prior CAR-T BCMA-antibody-drug conjugates therapy included, whereas those treatment bispecifics excluded. Results: affinity binding (with subnanomolar KD), effectively cells low expression, emerging mechanism resistance BCMA-targeted therapies. demonstrated potent efficient preclinical models, well tolerated As December 08, 2021, total 33 treated intravenous once weekly at following dose levels: 3, 6, 12, 24, 48, 64, 96, 192, 250 µg/kg body weight. Twenty-five (75.8%) discontinued due progressive disease (n=22), physician decision (n=2) adverse event (AE, n=1). most frequent (≥20%) treatment-related AEs (TRAEs) all grades across included cytokine release syndrome (CRS, 60.6%), pyrexia (39.4%), increased alanine aminotransferase (ALT, 30.3%), aspartate (AST) anemia (24.2% each), common grade ≥3 TRAEs (≥10%) AST, lymphopenia (18.2% ALT (15.2%), CRS neutropenia (12.1% each). Clinical observed starting 48 µg/kg. At active 48-250 (n=26), overall rate (partial better) 34.6% (n=9; 90% CI, 19.4-52.6) complete (stringent response+complete response) 11.5% (n=3; 3.2-27.2). maximum has not been reached. Pharmacokinetic showed trend towards dose-proportional relationship no evidence accumulation. Image:Summary/Conclusion: BsAb, favorable models. In study, exhibited acceptable profile preliminary evaluation as single combination gamma secretase inhibitor ongoing.