Findings from phase II of the phase I/II MajesTEC-1 study on teclistamab were presented for the first time at the 2021 Annual Meeting & Exposition of the American Society of Hematology (ASH), along with updated data from the phase I portion. According to the study’s lead author, Phillipe Moreau, MD, from the Hematology Clinic at the University Hospital Hôtel-Dieu in Nantes, France, teclistamab displayed a manageable safety profile at the recommended phase II dose and continued to produce meaningful and durable responses in patients with heavily pretreated relapsed or refractory multiple myeloma.
Teclistamab is a T-cell redirecting, bispecific IgG4 antibody that targets both B-cell maturation antigen (BCMA) and CD3 receptors to induce T-cell mediated cytotoxicity of BCMA-expressing myeloma cells. In phase I of the trial, researchers identified a recommended phase II dose of subcutaneous teclistamab 1500 µg/kg each week, following step-up doses of 60 and 300 µg/kg. As of June 14, 2021, 159 patients with a median of five prior lines of therapy were treated at the recommended dose. No new safety concerns were identified.
The most common nonhematologic adverse event (AE) among the whole cohort was cytokine release syndrome (CRS; 67%), which were grade I/II in 99% of cases. Other common AEs included injection site erythema (23%, all grade I/II) and fatigue (22%, grade III/IV: 2%). The most common hematologic AEs were neutropenia (53%, grade III/IV: 45%), anemia (41%, grade III/IV: 27%), and thrombocytopenia (33%, grade III/IV: 18%). Four patients developed grade I or II immune effector cell-associated neurotoxicity syndrome, which were resolved.
Among the 40 evaluable patients from the phase I portion of the study, teclistamab led to an overall response rate (ORR) of 65% and a very good partial response or better (≥VGPR) rate of 58% after a median of 6.1 months of follow-up.
Dr. Moreau stated that data from phase II supported the findings from phase I of the study. Efficacy data for the entire phase II cohort was not yet available, but, in the 40 phase I patients who continued to phase II, outcomes were consistent with the earlier results, including an ORR of 65%, a ≥VGPR rate of 60%, and a complete response or better rate of 40%.
The study’s authors concluded that teclistamab’s safety was supported by the updated data. Also, while full efficacy data were not available as of presentation, they noted that the observable responses had deepened over time and were sustained in patients with relapsed or refractory multiple myeloma.