Phase I study of teclistamab, a humanized B-cell maturation antigen (BCMA) x CD3 bispecific antibody, in relapsed/refractory multiple myeloma (R/R MM).
Abstract No : 100
Abstract Type : Clinical Science Symposium
Indication : Multiple Myeloma
Intervention : Teclistamab
Company : Janssen R&D
Technology : BCMA Inhibitor
As of 31 Jan 2020, 66 pts had received iv teclistamab (0.3–270 µg/kg). Median age was 64 y (24–82), median prior therapies was 6 (2–14), 97% triple-class exposed, 83% triple-class refractory, and 38% penta-drug refractory. Most common treatment-related AEs (all grade) were CRS (56%), neutropenia (26%), and anemia (23%). CRS events were all grade 1–2 and generally confined to initial doses. 8% of pts had treatment-related neurotoxicity (3% grade ≥3), and 9% had infusion related reaction. Infection-related AEs were reported in 61% of pts (21% grade ≥3). 2 dose-limiting toxicities were reported: grade 4 delirium (resolved after 16 days) and grade 4 thrombocytopenia (resolved after 1 day). 36% of pts had treatment-related grade ≥3 AEs; neutropenia (20%) and anemia (14%) were most frequent. Only 1 grade 5 AE was reported (respiratory failure in the setting of pneumonia deemed unrelated by the investigator). PK results indicate that the half-life of teclistamab supports weekly dosing. On-target pharmacodynamic activity (T cell redistribution and activation along with transient release of cytokines) was observed at doses ≥9.6 µg/kg. Cytokine production was modulated with step-up dosing while T cell activation was maintained. 65 pts were evaluable for response. Activity was observed starting at treatment doses ≥38.4 µg/kg, with 20/52 (38%) pts achieving a response. At the highest dose, 7/9 (78%) pts responded (1 response pending confirmation). Of MRD-evaluable pts who had complete response, 2/2 were MRD negative at 10−6 with treatment ongoing > 12 mo.
Teclistamab has manageable safety across all doses explored. A 78% overall response rate was observed at the highest weekly treatment dose in pts with advanced RRMM, supporting further evaluation of teclistamab in expansion cohorts.
Initial findings for teclistamab in highly pre-treated patients support further study of this investigational dual-targeting immunotherapeutic.