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