Teclistamab, a B-cell maturation antigen × CD3 bispecific antibody, in patients with relapsed or refractory multiple myeloma (MajesTEC-1): a multicentre, open-label, single-arm, phase 1 study
Mené sur 157 patients atteints d'un myélome multiple réfractaire ou récidivant, cet essai de phase I évalue la dose maximale tolérée, et l'efficacité, du point de vue du taux de réponse globale, du teclistamab, un anticorps bispécifique ciblant l'antigène de maturation des cellules B (BCMA) et les récepteurs CD3
Background : There is a need for novel therapies for relapsed or refractory multiple myeloma, and B-cell maturation antigen (BCMA) is a validated target. Teclistamab is a bispecific antibody that binds BCMA and CD3 to redirect T cells to multiple myeloma cells. Theaim of the MajesTEC-1 study was to evaluate the safety, tolerability, and preliminary efficacy of teclistamab in patients with relapsed or refractory multiple myeloma. Methods : This open-label, single-arm, phase 1 study enrolled patients with multiple myelomawho were relapsed, refractory, or intolerant to established therapies. Teclistamabwas administered intravenously (range 0·3−19·2
μg/kg [once every 2 weeks] or 19
·2−720
μg/kg [once per week]) or subcutaneously (range 80
−3000
μg/kg [once per week]) indifferent cohorts, with step-up dosing for 38
·4
μg/kg or higher doses. The primary
objectives were to identify the recommended phase 2 dose (part one) and characteriseteclistamab safety and tolerability at the recommended phase 2 dose (part two). Safetywas assessed in all patients treated with at least one dose of teclistamab. Efficacy
was analysed in response-evaluable patients (ie, patients who received at least onedose of teclistamab and had at least one post-baseline response evaluation). Thisongoing trial is registered with ClinicalTrials.gov, NCT03145181. Findings
:
Between June 8, 2017, and March 29, 2021, 219 patients were screened for study inclusion,and 157 patients (median six previous therapy lines) were enrolled and received atleast one dose of teclistamab (intravenous n=84; subcutaneous n=73). 40 patients wereadministered the recommended phase 2 dose, identified as once per week subcutaneousadministration of teclistamab at 1500 μg/kg, after 60 μg/kg and 300 μg/kg step-updoses (median follow-up 6
·1 months, IQR 3·6−8·2). There were no dose-limiting toxicitiesat the recommended phase 2 dose in part one. In the 40 patients treated at the recommendedphase 2 dose, the most common treatment-emergent adverse events were cytokine releasesyndrome in 28 (70%; all grade 1 or 2 events) and neutropenia in 26 (65%) patients(grade 3 or 4 in 16 [40%]). The overall response rate in response-evaluable patientstreated at the recommended phase 2 dose (n=40) was 65% (95% CI 48−79); 58% achieveda very good partial response or better. At the recommended phase 2 dose, the medianduration of response was not reached. 22 (85%) of 26 responders were alive and continuingtreatment after 7·1 months’ median follow-up (IQR 5·1−9·1). At the recommended phase2 dose, teclistamab exposure was maintained above target exposure levels, and consistentT-cell activation was reported. Interpretation : Teclistamab is a novel treatment approach for relapsed or refractory multiple myeloma.At the recommended phase 2 dose, teclistamab showed promising efficacy, with durableresponses that deepened over time, and was well tolerated, supporting further clinicaldevelopment.
The Lancet 2021