Favorable efficacy and manageable safety are shown in the updated analysis of the phase 1 study of teclistamab in patients with relapsed/refractory multiple myeloma (RRMM). This analysis supports the planned phase 2 monotherapy trial at 1500 µg/kg administered subcutaneously.
For patients who were intravenously administered teclistamab, a B-cell maturation antigen (BCMA) × CD3 bispecific antibody in RRMM, favorable phase 1 study results were previously presented. 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.
Intravenous (0.3-720 µg/kg) and subcutaneous (80-3000 µg/kg) teclistamab was given to a total of 84 and 44 patients, respectively. Median age was 64 years, and the median number of prior lines of therapies was 6. Although 95% and 79% of patients were triple-class exposed/refractory, 70% and 38% 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 intravenous dosing. After weekly intravenous or subcutaneous treatment, exposures increased in a dose-related manner. A subcutaneous dose of 1500 µg/kg had a comparable Cmax to an intravenous dose of 270 µg/kg. However, higher trough levels versus a 720-µg/kg intravenous dose occurred. Time to reach Cmax (Tmax) after subcutaneous dosing ranged from 3 to 8 days.
The most common hematologic adverse events (AEs) were anemia (55%), neutropenia (55%), thrombocytopenia (41%), and leukopenia (26%). The most common nonhematologic events were cytokine release syndrome (CRS; 53%), pyrexia (28%), diarrhea (24%), cough (23%), fatigue (23%), nausea (22%), back pain (20%), and headache (20%). In 39% of patients, grade ≥3 AEs occurred; neutropenia (23%) and anemia (9%) were the most common. In 55% and 50% of patients with intravenous and subcutaneous dosing, respectively, CRS (any grade) developed; events were observed within a median of 1 day later with subcutaneous administration. All CRS events were grade 1/2 and tended to occur with the initial dose(s). Neurotoxicity was experienced by 5% of patients among those who received intravenous administration (2% were grade ≥3), treatment-related infusion-related reactions were experienced by 5% of patients (all grade 1/2), and grade 5 AEs were reported in 4 patients but determined to be unrelated to treatment by the investigator, with the exception of 1 case of pneumonia. In 25% of patients who received the subcutaneous administration (all grade 1/2), injection-related reactions were experienced. In 15% of patients, infection-related AEs ≥grade 3 were observed; 3% were treatment-related.
Among the 120 patients with evaluable data across 4 intravenous and subcutaneous dose levels (intravenous: 270 µg/kg and 720 µg/kg weekly; subcutaneous: 720 µg/kg and 1500 µg/kg weekly), the overall response rate was 63.8% (30 of 47 patients specifically included in the response analysis, including N = 24 with ≥very good partial response [VGPR] and N = 9 with ≥complete response [CR]). Response data for patients who received a 3000-µg/kg subcutaneous dose are not yet available. However, the 1500-µg/kg subcutaneous dose was selected for phase 2 investigation. Six of 6 patients on this dose continue to be in response (3 partial response, 1 VGPR, 2 stringent CRs); responses deepened over time. Among 48 patients with responses in both cohorts, median time to first response was 1 month, whereas 38 responding patients remain on therapy for 1.6 to ≥21.3 months (thus, median duration of response has not yet been reached). Among patients in CR evaluable for minimal residual disease (MRD), 4 of 5 patients in the intravenous cohorts and 2 of 2 patients in the subcutaneous cohorts were MRD-negative at 10-6.
In patients with RRMM, 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.
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).