Favorable results from a phase 1 study were previously presented for intravenously administered teclistamab (JNJ-7957), a B-cell maturation antigen (BCMA) x CD3 bispecific antibody, in relapsed/refractory multiple myeloma (RRMM). The primary objective was to identify the dose(s) to be used in the phase 2 investigation. Updated results and data for subcutaneous administration are now available.
A total of 84 and 65 patients received intravenous (IV; 0.3-720 μg/kg) and subcutaneous (SC; 80-3000 μg/kg) teclistamab, respectively. The median age was 63 years, and the median number of prior lines of therapy was 6. Whereas 96% and 81% of patients were triple-class exposed/refractory, 69% and 39% of patients were penta-drug exposed/refractory, and 91% of patients were refractory to their last line of therapy.
Regarding pharmacokinetics, the half-life of teclistamab supports weekly IV dosing. Following weekly IV or SC treatment, exposures increased in a dose-related manner. An SC dose of 1500 μg/kg had a comparable maximum serum concentration (Cmax) to an IV dose of 270 μg/kg, but higher trough levels versus a 720-μg/kg IV dose. Time to reach Cmax following SC dosing ranged from 3 to 8 days.
The most common hematologic adverse events (AEs) were anemia (55%), neutropenia (57%), thrombocytopenia (40%), and leukopenia (28%), whereas the most common nonhematologic AEs were cytokine release syndrome (CRS; 55%), pyrexia (30%), diarrhea (23%), cough (21%), fatigue (22%), nausea (22%), and headache (22%). Grade ≥3 AEs occurred in 39% of patients; neutropenia (18%) and anemia (12%) were the most common. CRS (any grade) developed in 54% and 57% of patients with IV and SC dosing, respectively; events were observed within a median of 1 day after SC administration. All CRS events were grade 1/2 and tended to occur with the initial 1 to 2 dose(s). Among patients who received IV administration, 5% of patients experienced neurotoxicity (2 AEs being grade ≥3), 5% of patients experienced treatment-related infusion-related reactions (all grade 1/2), and grade 5 AEs were reported in 4 patients but were deemed unrelated to treatment by the investigator, with the exception of 1 case of pneumonia. Injection-site reactions were experienced by 22% of patients who received SC administration (all grade 1/2). Grade ≥3 infection-related AEs were observed in 15% of patients. The maximum tolerated dose has not been reached.
The overall response rate among the 120 patients with evaluable data across 4 IV and SC dose-level ranges (IV, 270-720 μg/kg weekly; SC, 720-1500 μg/kg weekly) was 69% (47 of 68 patients specifically included in the response analysis, including 40 with very good partial response or better [≥VGPR] and 18 with complete response or better [≥CR]). Although response data for patients who received a 3000-μg/kg SC dose are not yet available, the 1500-μg/kg SC dose was selected for phase 2 investigation and 15 of 16 patients on this dose continue to be in response (3 partial response, 5 VGPR, 4 CR, and 3 stringent CR), with responses deepening over time. The median time to first response among 35 patients with responses in the SC cohort was 1 month, whereas 32 responding patients remain on therapy for 1.7 months to 14 months after a median follow-up of 6.5 months. Among patients in CR evaluable for minimal residual disease (MRD), 5 of 5 patients across the IV and SC cohorts have sustained MRD-negativity at 10–6.
Favorable efficacy and safety results from this updated analysis of a phase 1 study support the planned phase 2 monotherapy trial of teclistamab 1500 μg/kg administered subcutaneously in patients with RRMM.
Abstract 180. ASH 2020. December 5, 2020. Updated Phase 1 Results of Teclistamab, a B-Cell Maturation Antigen (BCMA) x CD3 Bispecific Antibody, in Relapsed and/or Refractory Multiple Myeloma (RRMM).