Background: Teclistamab (JNJ-64007957), a bispecific antibody targeting both B-cell maturation antigen (BCMA) and CD3 receptors, mediates T cell activation and subsequent lysis of BCMA-expressing myeloma cells. In the multi-cohort, open-label, phase 1/2 MajesTEC-1 (NCT03145181) study, the safety and efficacy of teclistamab in patients with relapsed/refractory multiple myeloma (RRMM) who previously received ≥3 lines of therapy (LOT) are being investigated. In phase 1, weekly subcutaneous dose of teclistamab 1.5 mg/kg, preceded by step-up doses of 0.06 and 0.3 mg/kg, was identified as the recommended phase 2 dose (RP2D). Initial results from phase 1/2 showed that teclistamab at the RP2D was well tolerated and provided encouraging efficacy in patients with no prior exposure to an anti–BCMA-targeted treatment.
Aims: We report updated efficacy and safety results from MajesTEC-1 in patients treated at the RP2D, including additional patients and longer follow-up.
Methods: MajesTEC-1 included patients aged ≥18 years with documented MM (as per the International Myeloma Working Group [IMWG] criteria) who had received ≥3 prior LOT including a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 antibody. Patients previously exposed to BCMA-targeted therapy were not eligible in Phase 1. Patients received teclistamab at the RP2D. Overall response rate (ORR, assessed per the IMWG 2016 criteria) was the primary endpoint. CTCAE v4.03 (cytokine release syndrome [CRS] and ICANS graded per ASTCT guidelines) was used for grading adverse events (AEs). Results are based on a Sep 7, 2021 data cutoff for safety and a Nov 9, 2021 data cutoff for efficacy (N=165).
Results: The median age was 64 y (range 33–84), 58% were male, and patients had received 5 (range 2–14) median prior LOT; 100% of patients were triple-class exposed, 78% were triple-class refractory, 70% were penta-drug exposed, and 30% were penta-drug refractory. ORR was 64% (95% CI 56–72), with 30% of patients achieving a complete response or better. Durable responses were observed, which deepened over time. The 12-month duration of response (DOR) rate was 66% (95% CI 49–79); median DOR was not reached. A reduction in soluble BCMA was observed in the first cycle of treatment in a majority of patients who responded to teclistamab. Neutropenia (65%; grade 3/4: 57%), anemia (50%; grade 3/4: 35%), thrombocytopenia (38%; grade 3/4: 21%), and lymphopenia (34%; grade 3/4: 32%) were the most common hematologic AEs. Infections occurred in 104 patients (63%; grade 3/4: 35%). The most common nonhematologic AE was CRS in 72% patients (grade 3, 0.6%; no grade 4/5). The median (range) time to CRS onset was 2 days (1–6) and median duration was 2 days (1–9). A total of 9 ICANS events (all grade 1/2; all resolved) were reported in 5 (3%) patients, of which 7 ICANS events were concurrent with CRS (all resolved). No dose reductions due to AEs were required, and no treatment-related deaths were reported.
Summary/Conclusion: The deep and durable responses achieved with teclistamab in patients with highly refractory MM were reaffirmed with data from ~9 months of follow-up. No new safety signals were identified. Additional data with longer follow-up, including subgroup analyses and progression-free survival, will be presented.