Phase 1/2 Trial Results Underscore Teclistamab’s Efficacy in RRMM

Updated results of the MajesTEC -1 phase 1/2 study on teclistamab showed the treatment resulted in an overall response rate of 62% among heavily pretreated patients with multiple myeloma.

Updated results of the MajesTEC-1 phase 1/2 study on teclistamab showed the treatment resulted in an overall response rate (ORR) of 62% (95% CI, 53.7%-69.8%) among patients with relapsed/refractory multiple myeloma (RRMM), suggesting treatment responses were durable and deepened over time.

Additional findings were presented at the 63rd Annual American Society of Hematology Annual Meeting and Exposition, which took place December 11 -14 in Atlanta, Georgia.

Teclistamab is a T-cell redirecting, bispecific IgG4 antibody that targets the B-cell maturation antigen (BCMA) and CD3 receptors to induce T-cell–mediated cytotoxicity of BCMA-expressing myeloma cells, researchers explained.

The off-the-shelf therapy is manufactured by Janssen and received a Breakthrough Therapy Designation by the FDA in June 2021. Prior preclinical studies revealed teclistamab killed myeloma cell lines and bone-marrow–derived myeloma cells.

The ORR was reported after a median follow-up of nearly 8 months in 150 patients who received the recommended subcutaneous (SC) phase 2 dose (RP2D) of 1.5 mg/kg across the phase 1 and 2 studies. All participants had received at least 3 prior lines of therapy and were triple-class exposed.

In the phase 1 study, the researchers sought to identify the SC RP2D and characterize the treatment’s safety and tolerability; phase 2 was carried out to determine efficacy at RP2D.

Among responders, the median time to first confirmed response was 1.2 months (range, 0.2-5.5), while the ORR was consistent independent of cytogenetic risk or extent of prior therapy refractoriness.

However, median duration of response was not reached at the clinical cutoff; at this time, 92 of 93 responders were alive and continuing treatment. Median overall survival was also not reached.

Additional findings include:

  • 58% of patients receiving teclistamab achieved a very good partial response (VGPR) or better
  • 29% achieved a complete response (CR) or better
  • 21% achieved a stringent complete response
  • By intent to treat, 25% of patients achieved minimal residual disease (MRD) negativity at a threshold of 10-5 (95% CI, 18-32.4)
  • In patients who achieved CR or better, the MRD negativity rate was 42%
  • Progression-free survival rate at 9 months was 59% (95% CI, 48.8%-67.0%)

Throughout the course of the trial, no patients required a dose reduction and the most commonly reported adverse events (AEs) were cytokine release syndrome (CRS; 72%), injection-site erythema (26%), and fatigue (25%). One patient discontinued use due to adenoviral pneumonia. All CRS events were low grade, with the exception of 1 grade 3 event, and all resolved without treatment discontinuation.

Neutropenia, anemia, and thrombocytopenia were the most common hematologic AEs reported, while 5 patients developed immune effector cell–associated neurotoxicity syndrome.

A phase 3 study is currently underway, in part to evaluative the treatment in earlier-line settings and in combination with other agents. Additional data regarding patients with prior BCMA will also be reported.

Reference

Moreau P, Usmani SZ, Garfall A, 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. Presentation presented at: 63rd American Society of Hematology (ASH) Annual Meeting & Exposition; December 11-14, 2021; Atlanta, GA. Virtual.