Contributions
Abstract: S206
Type: Oral Presentation
Session title: Management of relapsed/refractory multiple myeloma and minimal residual disease assessment
Background
BCMA is predominantly expressed on the surface of terminally differentiated B-cells, and soluble BCMA levels correlate with disease progression in MM. Teclistamab is a humanized BCMA x CD3 bispecific antibody that redirects CD3-expressing T cells to BCMA-expressing myeloma cells to induce T cell-mediated cytotoxicity against myeloma cells. In a MM xenograft model, teclistamab inhibited tumor growth with concomitant induction of cytokine release and T cell activation.
Aims
To present initial safety and efficacy results from an ongoing phase 1 study of teclistamab in patients with RRMM (NCT03145181).
Methods
Eligible patients had MM and had relapsed on or were refractory to standard therapies. All patients provided informed consent. The study comprised a dose escalation phase (part 1) and a dose expansion phase (part 2). The primary objective for part 1 was to identify a recommended phase 2 dose(s) by exploring multiple intravenous doses ± priming doses. Adverse events (AEs) were graded per Common Terminology Criteria for Adverse Events v4.03, and cytokine release syndrome (CRS) was graded by Lee et al. (Blood 2014;124:188). Response was assessed by the investigator using International Myeloma Working Group criteria, and minimal residual disease (MRD) in bone marrow was assessed by next generation sequencing.
Results
As of January 31, 2020, 66 patients across 16 cohorts had received intravenous teclistamab (dose range, 0.3–270 µg/kg). Median age was 64 years (range, 24–82), median prior therapies was 6 (range, 2–14), 97% were triple-class exposed, 83% triple-class refractory, and 38% penta-drug refractory. Most common treatment-related AEs of any grade were CRS (56%), neutropenia (26%), and anemia (23%). All CRS events were grade 1–2 and generally confined to initial doses. Overall, 9% of patients had infusion related reaction, and 8% had treatment-related neurotoxicity (3% with grade ≥3). Infection-related AEs were reported in 61% of patients (21% with grade ≥3). Two dose-limiting toxicities were reported: grade 4 delirium (resolved after 16 days) and grade 4 thrombocytopenia (resolved after 1 day). Treatment-related grade ≥3 AEs were reported in 36% of patients; the most frequent were neutropenia (20%) and anemia (14%). Only one grade 5 AE was reported (respiratory failure in the setting of pneumonia), which was deemed unrelated to treatment by the investigator.
PK results indicated that the half-life of teclistamab supports weekly dosing. On-target pharmacodynamic activity (T cell redistribution and activation along with transient release of cytokines) was observed at doses ≥9.6 µg/kg. Cytokine production was modulated with step-up dosing while T cell activation was maintained.
Overall, 65 patients were evaluable for response. Activity was observed starting at treatment doses ≥38.4 µg/kg, with 20/52 (38%) patients achieving a response. At the highest dose, 7/9 (78%) patients responded (1 response pending confirmation). Of the MRD-evaluable patients who had complete response, 2/2 were MRD negative at 10-6 level of sensitivity, with treatment ongoing >12 months.
Conclusion
Teclistamab has a manageable safety profile across all doses explored. At the highest weekly treatment dose, a 78% overall response rate was observed in patients with advanced RRMM, supporting further evaluation of teclistamab in expansion cohorts.
Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical
Keyword(s): B-cell maturation antigen, Multiple myeloma, Refractory
Abstract: S206
Type: Oral Presentation
Session title: Management of relapsed/refractory multiple myeloma and minimal residual disease assessment
Background
BCMA is predominantly expressed on the surface of terminally differentiated B-cells, and soluble BCMA levels correlate with disease progression in MM. Teclistamab is a humanized BCMA x CD3 bispecific antibody that redirects CD3-expressing T cells to BCMA-expressing myeloma cells to induce T cell-mediated cytotoxicity against myeloma cells. In a MM xenograft model, teclistamab inhibited tumor growth with concomitant induction of cytokine release and T cell activation.
Aims
To present initial safety and efficacy results from an ongoing phase 1 study of teclistamab in patients with RRMM (NCT03145181).
Methods
Eligible patients had MM and had relapsed on or were refractory to standard therapies. All patients provided informed consent. The study comprised a dose escalation phase (part 1) and a dose expansion phase (part 2). The primary objective for part 1 was to identify a recommended phase 2 dose(s) by exploring multiple intravenous doses ± priming doses. Adverse events (AEs) were graded per Common Terminology Criteria for Adverse Events v4.03, and cytokine release syndrome (CRS) was graded by Lee et al. (Blood 2014;124:188). Response was assessed by the investigator using International Myeloma Working Group criteria, and minimal residual disease (MRD) in bone marrow was assessed by next generation sequencing.
Results
As of January 31, 2020, 66 patients across 16 cohorts had received intravenous teclistamab (dose range, 0.3–270 µg/kg). Median age was 64 years (range, 24–82), median prior therapies was 6 (range, 2–14), 97% were triple-class exposed, 83% triple-class refractory, and 38% penta-drug refractory. Most common treatment-related AEs of any grade were CRS (56%), neutropenia (26%), and anemia (23%). All CRS events were grade 1–2 and generally confined to initial doses. Overall, 9% of patients had infusion related reaction, and 8% had treatment-related neurotoxicity (3% with grade ≥3). Infection-related AEs were reported in 61% of patients (21% with grade ≥3). Two dose-limiting toxicities were reported: grade 4 delirium (resolved after 16 days) and grade 4 thrombocytopenia (resolved after 1 day). Treatment-related grade ≥3 AEs were reported in 36% of patients; the most frequent were neutropenia (20%) and anemia (14%). Only one grade 5 AE was reported (respiratory failure in the setting of pneumonia), which was deemed unrelated to treatment by the investigator.
PK results indicated that the half-life of teclistamab supports weekly dosing. On-target pharmacodynamic activity (T cell redistribution and activation along with transient release of cytokines) was observed at doses ≥9.6 µg/kg. Cytokine production was modulated with step-up dosing while T cell activation was maintained.
Overall, 65 patients were evaluable for response. Activity was observed starting at treatment doses ≥38.4 µg/kg, with 20/52 (38%) patients achieving a response. At the highest dose, 7/9 (78%) patients responded (1 response pending confirmation). Of the MRD-evaluable patients who had complete response, 2/2 were MRD negative at 10-6 level of sensitivity, with treatment ongoing >12 months.
Conclusion
Teclistamab has a manageable safety profile across all doses explored. At the highest weekly treatment dose, a 78% overall response rate was observed in patients with advanced RRMM, supporting further evaluation of teclistamab in expansion cohorts.
Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical
Keyword(s): B-cell maturation antigen, Multiple myeloma, Refractory