Teclistamab Continues to Produce Durable Responses in MajesTEC-1 Trial

Take-aways:

• Teclistamab targets both B-cell maturation antigen (BCMA) and CD3 receptors to induce T-cell mediated cytotoxicity of BCMA-expressing myeloma cells.
• In updated data from MajesTEC-1, teclistamab led to an overall response rate of 65% and a complete response or better rate of 40%.
• Two-thirds of patients developed cytokine release syndrome, which was grade I/II in 99% of cases.

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The bispecific antibody teclistamab produced meaningful and durable responses in patients with heavily pretreated relapsed or refractory multiple myeloma and had a manageable safety profile at the recommended phase II dose. These results were shared in an update from phase II of the phase I/II MajesTEC-1 study, along with updated data from the phase I portion, at the 2021 ASH Annual Meeting.

Teclistamab 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 1.5 mg/kg each week, following step-up doses of 60 and 300 µg/kg. As of data presentations, 165 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; 71.5%); most cases were grade 1 or 2, with 1 patient experiencing grade 3 CRS. The investigators noted that all CRS events were resolved and none led to treatment discontinuation. Other common AEs included hypogammaglobulinemia (72.1%) and injection site erythema (35.2%).

In total, 9 patients died from AEs, but no patient deaths were considered related to teclistamab. Four patients developed grade I or II immune effector cell-associated neurotoxicity syndrome, which were resolved.

Among the 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. Neither the median duration of response or median overall survival were reached, but the authors noted that, among patients who responded to teclistamab, the 6-month event-free survival rate was 92.5% and 85.9% at 9 months. The six-month progression-free survival (PFS) rate was 64.4% and the 9-month PFS rate was 58.5%.

The investigators stated that data from phase II of the trial 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 date, they noted that the observable responses had deepened over time and were sustained in patients with relapsed/refractory multiple myeloma.

Based on the data from this trial, the manufacturer of telistamab submitted a Marketing Authorisation Application to the European Medicines Agency seeking approval of teclistamab for the treatment of patients with relapsed or refractory multiple myeloma.

Disclosures: This research was supported by Janssen Research & Development, LLC. Study authors report financial relationships with Janssen, the manufacturer of teclistamab.

Reference

Moreau P, Usmani SZ, Garfall AL, et al. Updated results from MajesTEC-1: phase 1/2 study of teclistamab, a B-cell maturation antigen x CD3 bispecific antibody, in relapsed/refractory multiple myeloma. Presented at the 2021 ASH Annual Meeting, December 13, 2021.