Teclistamab Shows Durable Responses in Heavily Pretreated Patients With R/R MM

The MajesTEC-1 trial, an ongoing phase 1/2 study, found teclistamab was well tolerated at the recommended phase 2 dose (RP2D) with encouraging efficacy in patients with heavily pretreated relapsed or refractory (R/R) multiple myeloma (MM).

“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,” explained Philippe Moreau, MD, PhD, University Hospital Hôtel-Dieu, France, and co-investigators.

Patients enrolled to the trial were diagnosed with MM, had measurable disease, and were exposed to a proteasome inhibitor, immunomodulatory drug, and an anti-CD38 antibody.

During the phase 1 duration of the trial, the primary objectives were to identify the RP2D and to characterize safety and tolerability. In phase 2, the primary objective was to evaluate the efficacy of teclistamab and the primary endpoint was overall response rate (ORR).

A total of 159 patients received a weekly R2PD of subcutaneous teclistamab 1500 µg/kg following step-up doses of 60 and 300 µg/kg. Further, patients received a median of 5 prior lines of therapy (range: 2-15), 100% were triple-class exposed, 69% were penta-drug exposed, 77% were triple-class refractory, and 29% were penta-drug refractory.

“Efficacy data for the phase 2 study are immature. At a median follow-up of 8.2 months (range 1.2-15.2), response rates in the 40 phase 1 patients treated at RP2D were consistent with previously presented data (ORR: 65% [95% CI, 48-79]; ≥very good partial response rate: 60% [95% CI 43–75]; complete response or better rate: 40% [95% CI 25–57]),” elaborated Dr Moreau and co-authors.

The researchers found responses deepened over time and longer follow-up of responders compared with previously presented data (median follow-up of 9.5 months vs 7.1 months) remained durable.

“No additional responders had disease progression, and 85% of responders are continuing treatment, including 1 patient with 15.2 months of follow-up. Median duration of response (DOR) has not been reached. The 6-month DOR rate is 90% (95% CI, 63-97),” continued Dr Moreau and co-investigators.

Reported nonhematologic adverse events (AEs) were cytokine release syndrome (67%), injection site erythema (23%), and fatigue (22%). The most common hematologic AEs were neutropenia (53%), anemia (41%), and thrombocytopenia (33%). No deaths were reported.

“Evaluation of teclistamab at the RP2D in 159 patients provides robust data to support safety. Data from MajesTEC-1 continue to show that teclistamab monotherapy induces deep and durable responses in heavily pretreated patients with R/R MM with a manageable safety profile,” concluded Dr Moreau, et al. –Alexa Stoia

Moreau P, Usmani S, Garfall A, et al. Updated Results from MajesTEC-1: Phase ½ Study of Teclistamab, a B-Cell Maturation Antigen x CD3 Bispecific Antibody, in Relapsed/Refractory Multiple Myeloma. Presented at: the 2021 ASH Annual Meeting; Dec. 11-14; 2021; Abstract 896.