A novel, immunotherapy-based approach for the treatment of relapsed/refractory multiple myeloma (RRMM): Updated phase 1b results for daratumumab in combination with teclistamab (a BCMA x CD3 bispecific antibody).

• DOI: 10.1200/jco.2022.40.16_suppl.8032
• Publication Date: 2022-06-06T17:16:22Z
• Authors: Paula Rodríguez-O...; Anita D'Souza; Donna Ellen Reece; Niels W.C.J. van ...; Ajai Chari; Amrita Y. Krishnan; Thomas G. Martin; Maria-Victoria Ma...; Daniel Morillo; David Duane Hurd; Laura Rosiñol; Anna Sureda Balari; Ralph Wäsch; Deeksha Vishwamitra; Shun Xin Wang Lin; Thomas Prior; Lien Vandenberk; Marie-Anne Damiet...; Albert Oriol Roca...; Bhagirathbhai R. ...
• Keywords: Daratumumab; Cytokine Release Syndrome

8032 Background: Teclistamab (tec; JNJ-64007957) is a BCMA × CD3 T-cell redirecting bispecific antibody under investigation in patients (pts) with RRMM. Daratumumab (dara) CD38 mAb direct on-tumor and immunomodulatory actions. Initial clinical data from the phase 1b multicohort TRIMM-2 study support combination of tec + dara for treatment RRMM, tolerable safety, no overlapping toxicities, promising efficacy. We present updated results additional pts longer follow-up. Methods: Eligible MM aged ≥18 y had received ≥3 prior lines therapy (LOT; including proteosome inhibitor [PI] drug [IMiD]) or were double-refractory to PI IMiD. Pts treated anti-CD38 ≤90 d excluded. SC 1800 mg per approved schedule 1.5–3 mg/kg QW Q2W. Primary objectives identify recommended 2 dose evaluate safety combination. Responses assessed by IMWG criteria. AEs graded CTCAE v5.0; cytokine release syndrome (CRS) immune effector cell–associated neurotoxicity (ICANS) ASTCT guidelines. Results: At cutoff (Jan 13, 2022; population: N=46), median follow-up was 7.2 mo (range 0.1–16.6; age 67 [range 50–79]; 52% female). 6 LOT 2–17; 74% triple-class exposed; 63% penta-drug 15% anti-BCMA exposed). 91% ≥1 AE (grade 3/4 78%), most commonly CRS (61%; all grade 1/2; time onset d; duration d), neutropenia (54%; 50%), anemia (46%; 28%), thrombocytopenia (33%; diarrhea 2%). Infections occurred 29 (63%; 28%). One pt 1 ICANS that fully resolved. Among 37 response-evaluable pts, ORR 78% (29/37); 27 (73%) very good partial response (VGPR) better (Table). Median first across dosing cohorts 1.0 0.9–2.8); not reached. Upregulation /CD8 T cells proinflammatory cytokines observed dara, supporting potential synergy exposure. Updated will be presented. Conclusions: Tec provides novel immunotherapy approach RRMM may yield improved efficacy heavily pretreated pts. Clinical trial information: NCT04108195. [Table: see text]