Updated Results from MajesTEC-1: Phase 1/2 Study of Teclistamab, a BCMA x CD3 Bispecific Antibody, in RRMM

2021 Year in Review - Multiple Myeloma

Data from the ongoing phase 1/2 MajesTEC-1 study suggested that treatment with the BCMA x CD3 bispecific antibody teclistamab induced deep and durable responses in heavily pretreated patients with RRMM, with a manageable safety profile.

Teclistamab (JNJ-64007957) is a T-cell–redirecting, bispecific IgG4 antibody that targets B-cell maturation antigen (BCMA) and CD3 receptors to induce T-cell–mediated cytotoxicity of BCMA-expressing myeloma cells. Teclistamab is under investigation in the MajesTEC-1 trial. The ongoing, 3-part, phase 1/2 MajesTEC-1 study is evaluating the BCMA x CD3 bispecific antibody teclistamab in patients with heavily pretreated relapsed/refractory multiple myeloma (RRMM). Results from the phase 1 portion of the study (parts 1 and 2) were previously reported and showed that teclistamab (median follow-up 6.1 months) was well-tolerated and had promising antitumor activity at the recommended phase 2 dose (RP2D). Updated results for the phase 1/2 portion of MajesTEC-1 (part 1-3) were reported at the 2021 ASH Annual Meeting and summarized here.

The study enrolled patients aged ≥18 years with MM diagnosis per International Myeloma Working Group criteria, who had measurable disease, and were exposed to a proteasome inhibitor, immunomodulatory drug, and anti-CD38 antibody. Patients were relapsed, refractory, or intolerant to established therapies (phase 1) or received ≥3 previous lines of therapy (phase 2). The primary objectives in phase 1 were to identify the RP2D and to characterize safety and tolerability of teclistamab at the RP2D. The primary objective in phase 2 was to evaluate the antitumor activity of teclistamab at the RP2D; the primary end point was investigator-assessed objective response rate. Patients treated at the RP2D received a weekly dose of subcutaneous teclistamab 1500 µg/kg following step-up doses of 60 µg/kg and 300 µg/kg. The data cutoff date was September 7, 2021.

In phases 1 and 2, a total of 165 patients were treated at the RP2D; of these, 40 patients were treated in phase 1 and 125 patients in phase 2. The median age of the total population was 64.0 years; 14.5% of patients were aged ≥75 years and 58.2% were male. In terms of previous lines of therapy, it was a heavily pretreated population, with a median of 5 previous lines of therapy; 100% were triple-class–exposed, 70.3% were penta-drug–exposed, 77.6% were triple-class refractory, and 30.3% were penta-drug refractory.

In phase 2, there were no new safety signals identified. In all patients treated at RP2D (N = 165), the most common nonhematologic adverse events (AEs) were cytokine release syndrome (71.5%), injection-site erythema (25.5%), and fatigue (24.8%). The majority of cytokine release syndrome events were grade 1/2; 1 patient had a transient grade 3 event. Median time to onset was 2 days (range, 1-6 days), and median duration was 2 days (range, 1-9 days). The most common hematologic AEs were neutropenia (65.5%), anemia (49.7%), and thrombocytopenia (38.2%). The majority of grade 3/4 AEs were hematologic toxicities, including neutropenia (57%), anemia (34.5%), and thrombocytopenia (21.2%). Five (3%) patients had immune effector-cell–associated neurotoxicity syndrome, all of which were grade 1/2 severity and resolved.

Pharmacokinetic data show that teclistamab exposure at the RP2D was sustained across the dosing interval and exceeded target exposure levels. Pharmacodynamic data for phase 1/2 patients treated at the RP2D showed induction of proinflammatory cytokines and T-cell activation.

In the phase 1 (N = 40) and phase 2 portion (N = 110) of the study, updated efficacy data (at a median follow-up of 7.8 months) showed that teclistamab treatment at RP2D yielded response rates of 62%, very good partial response or better rate of 58%, and complete response or better rate of 28.7%, which were consistent with previously reported data. Compared with previously reported data, responses among responders with longer follow-up were durable and deepened over time (median follow-up of 9.5 months vs 7.1 months). At data cutoff, the majority (91.4% [85 of 93]) of responders continued on treatment. Median duration of response has not been reached; the 6-month duration of response rate was 92.5%.

Data from the MajesTEC-1 study suggested that teclistamab monotherapy induced deep and durable responses in heavily pretreated patients with RRMM, with a manageable safety profile, warranting further investigation.

Source: 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. Blood. 2021;138(suppl 1):896.

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