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| Authors | Saad Zafar Usmani, Maria-Victoria Mateos, Hareth Nahi, Amrita Y. Krishnan, Niels W.C.J. van de Donk, Jesus San Miguel, Albert Oriol, Laura Rosiñol, Ajai Chari, Homer Adams, Suzette Girgis, Shun Xin Wang Lin, Tara Stephenson, Kristy Kemmerer, Jennifer Smit, Yusri A. Elsayed, Jeffrey R. Infante, Jenna D. Goldberg, Arnob Banerjee, Alfred L. Garfall | ||||||||||||
| Title | Phase I study of teclistamab, a humanized B-cell maturation antigen (BCMA) x CD3 bispecific antibody, in relapsed/refractory multiple myeloma (R/R MM). | ||||||||||||
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| URL | https://ascopubs.org/doi/abs/10.1200/JCO.2020.38.15_suppl.100 | ||||||||||||
| Abstract Text | Background: Teclistamab (JNJ-64007957) is a bispecific BCMA x CD3 antibody that induces T cell-mediated cytotoxicity against BCMA-expressing myeloma cells. Initial results from an ongoing study of teclistamab in RRMM (NCT03145181) are presented. Methods: Pts have MM and are RR to standard therapies. Primary objective for part 1 is to identify a recommended phase 2 dose(s). Multiple intravenous (iv) doses ± priming doses were explored. Adverse events (AEs) were graded per CTCAE v4.03 and cytokine release syndrome (CRS) per Lee et al 2014. Response was investigator-assessed using IMWG criteria; minimal residual disease (MRD) in bone marrow was assessed by next generation sequencing. Results: 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. Conclusions: 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. Clinical trial information: NCT03145181. | ||||||||||||
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