P06: UPDATED RESULTS FROM THE PHASE 1/2 MAJESTEC-1 STUDY OF TECLISTAMAB, A B-CELL MATURATION ANTIGEN X CD3 BISPECIFIC ANTIBODY, IN PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA
2022-04-01

Teclistamab (JNJ-64007957) is a bispecific antibody that binds to both B-cell maturation antigen (BCMA) and CD3 receptors to induce T cell-mediated cytotoxicity of BCMA-expressing myeloma cells. Results from phase 1 of the MajesTEC-1 study, an ongoing phase 1/2 study in heavily-pretreated relapsed/refractory multiple myeloma (RRMM; NCT03145181), showed a tolerable safety profile at the recommended phase 2 dose (RP2D) and encouraging efficacy. Here we report initial data from the phase 2 portion of MajesTEC-1 (NCT04557098) as well as updated results from phase 1. Patients (pts; ≥18 y) had MM per International Myeloma Working Group (IMWG) criteria, measurable disease, and were exposed to a proteasome inhibitor, immunomodulatory drug, and anti-CD38 antibody. In phase 1, pts were relapsed, refractory, or intolerant to established therapies. In phase 2, pts received ≥3 prior lines of therapy (LOT). The primary objectives were to identify the RP2D and to characterize safety and tolerability of teclistamab at the RP2D in phase 1, and to evaluate the efficacy at the RP2D (primary endpoint: ORR) in phase 2. The RP2D was weekly subcutaneous teclistamab 1500 μg/kg following step-up doses of 60 and 300 μg/kg. Responses were assessed by the investigator per IMWG criteria. Adverse events (AEs) were graded per CTCAE v4.03. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were graded per ASTCT criteria. As of June 14, 2021, 159 pts (median age 64.0 y [range 33–84]; 15% ≥75 y; 59% male) were treated at the RP2D (phase 1: 40 pts; phase 2: 119 pts). Pts received a median of 5 prior LOT (range 2–15); 100% were triple-class exposed, 69% were penta-drug exposed, 77% were triple-class refractory, and 29% were penta-drug refractory. In 159 pts, the most common nonhematologic AEs at the RP2D were CRS (any grade: 67%; grade 3 occurred in 1 pt, no grade 4 or 5), injection site erythema (23%; all grade 1/2), and fatigue (22%; grade 3/4: 2%). Of the hematologic AEs, most common were neutropenia (53%; grade 3/4: 45%), anemia (41%; grade 3/4: 27%), and thrombocytopenia (33%; grade 3/4: 18%). Four pts (2.5%) developed ICANS (all grade 1/2; all resolved). No new safety signals were identified in phase 2. Phase 2 pharmacokinetic and pharmacodynamic data supported those reported in phase 1. At the RP2D, teclistamab exposure was sustained across the dosing interval and exceeded target exposure levels. Across both phases, induction of proinflammatory cytokines and T cell activation were observed at the RP2D. Phase 2 efficacy data are immature. At 8.2-mo median follow-up (range 1.2–15.2), responses in the phase 1 pts at the RP2D (n=40) were consistent with previous reports (ORR: 65% [95% CI 48–79]; ≥VGPR: 60% [95% CI 43–75]; ≥complete response: 40% [95% CI 25–57]). Responses deepened over time, and with longer follow-up of responders compared with previously presented data (median follow-up of 9.5 mo vs 7.1 mo), remained durable (Figure). 85% (22/26) of responders are continuing on treatment, including 1 pt with 15.2 mo of follow-up. Median duration of response (DOR) was not reached, with 6-month DOR rate of 90% [95% CI 63–97]. The safety of teclistamab is supported by data from 159 pts treated at the RP2D. Teclistamab continues to show deep and durable responses with a manageable safety profile in heavily-pretreated pts with RRMM.