Updated phase 1 results of teclistamab, a B-cell maturation antigen (BCMA) × CD3 bispecific antibody, in relapsed/refractory multiple myeloma (MM).
Authors: Krishnan Amrita Y. , Garfall Alfred L. , Mateos Maria-Victoria , van de Donk Niels W.C.J. , Nahi Hareth , F. San-Miguel Jesús , Oriol Albert , Rosiñol Laura , Chari Ajai , Bhutani Manisha , Karlin Lionel , Benboubker Lotfi , Pei Lixia , Verona Raluca , Girgis Suzette , Stephenson Tara , Goldberg Jenna D. , Banerjee Arnob , Usmani Saad Zafar 
Published: June 2021

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Background: BCMA-targeted immunotherapies offer considerable promise for relapsed/refractory MM. Teclistamab (JNJ-64007957) is a BCMA × CD3 bispecific IgG4 antibody that redirects CD3+ T cells to BCMA-expressing MM cells. We present updated results of patients (pts) treated at the recommended phase 2 dose (RP2D) in the first-in-human phase 1 study of teclistamab. Methods: Eligible pts had MM and were relapsed, refractory or intolerant to established therapies. Primary objectives were to identify the RP2D (part 1) and characterize safety and tolerability of teclistamab at the RP2D (part 2). Teclistamab was given intravenously (IV; range 0.3–19.2 µg/kg [biweekly]; range 19.2–720 µg/kg [weekly]) or subcutaneously (SC; range 80.0–3000 µg/kg weekly) in different cohorts, with step-up dosing used for ≥38.4 µg/kg doses. Adverse events (AEs) were graded by CTCAE v4.03 (cytokine release syndrome [CRS] by Lee et al 2014). Response was assessed per IMWG criteria. Results: As of Feb 4, 2021, 156 pts received teclistamab (IV n = 84; SC n = 72). The RP2D, identified as weekly SC 1500 µg/kg teclistamab with 60.0 and 300 µg/kg step-up doses, was given to 40 pts (median follow-up 4.3 mo [range 1.1–10.4+]). Pts dosed at the RP2D (median age, 62.5 y [range, 39–84]; 65% male) had received a median of 5 prior lines of therapy (range 2–11; 100% triple-class exposed; 65% penta-drug exposed; 83% triple-class refractory; 35% penta-drug refractory; 85% refractory to their last line of therapy). There were no dose-limiting toxicities at the RP2D in part 1. The most common AEs at the RP2D were CRS (70%; grade 3/4 0) and neutropenia (60%; grade 3/4 40%); grade 1 neurotoxicity was reported in 1 (3%) pt. Median time to CRS onset was later with SC vs IV dosing (day after SC injection vs day of IV infusion). The overall response rate in response-evaluable pts treated at the RP2D (n = 40) was 65%; 58% achieved a very good partial response or better and 30% achieved a complete response (CR) or better; median time to first confirmed response was 1.0 mo (range 0.2–3.1). At the RP2D, median duration of response was not reached; 23 of 26 responders (88%), after median follow-up of 5.3 mo (range 1.2–10.4+), were alive and continuing on treatment with responses deepening over time. Of 14 evaluable pts across all cohorts, 9 with CR were minimal residual disease–negative at 10-6. At the RP2D, teclistamab exposure was sustained across the dosing interval and exceeded target levels, and consistent T cell activation was observed. Conclusions: Teclistamab at the RP2D (weekly 1500 µg/kg SC) was well-tolerated and showed encouraging efficacy with durable, deepening responses, supporting further investigation as monotherapy and in combination with other agents. With the extended exposure profile at the RP2D and delayed and low-grade CRS observed with SC administration, alternative SC dosing strategies are being explored. Clinical trial information: NCT03145181.