A PHASE 1 STUDY OF TECLISTAMAB, A HUMANIZED B-CELL MATURATION ANTIGEN (BCMA) X CD3 BISPECIFIC ANTIBODY, FOR THE TREATMENT OF RELAPSED AND/OR REFRACTORY MULTIPLE MYELOMA (RRMM)
Author(s): ,
Maria-Victoria Mateos
Affiliations:
University Hospital of Salamanca,Salamanca,Spain
,
Saad Z. Usmani
Affiliations:
Levine Cancer Institute-Atrium Health,Charlotte,United States
,
Hareth Nahi
Affiliations:
Karolinska University Hospital at Huddinge,Stockholm,Sweden
,
Amrita Y. Krishnan
Affiliations:
City of Hope,Duarte,United States
,
Jesus F. San-Miguel
Affiliations:
Clínica Universidad de Navarra,Navarra,Spain
,
Albert Oriol
Affiliations:
Institut Català d'Oncologia and Institut Josep Carreras. Hospital Germans Trias i Pujol,Barcelona,Spain
,
Laura Rosinol
Affiliations:
Hospital Clinic,Barcelona,Spain
,
Ajai Chari
Affiliations:
Mount Sinai School of Medicine,New York,United States
,
Homer Adams III
Affiliations:
Janssen R&D,Spring House,United States
,
Suzette Girgis
Affiliations:
Janssen R&D,Spring House,United States
,
Shun Xin Wang Lin
Affiliations:
Janssen R&D,Spring House,United States
,
Tara Stephenson
Affiliations:
Janssen R&D,Spring House,United States
,
Kristy Kemmerer
Affiliations:
Janssen R&D,Spring House,United States
,
Jennifer Smit
Affiliations:
Janssen R&D,Spring House,United States
,
Yusri A. Elsayed
Affiliations:
Janssen R&D,Spring House,United States
,
Jeffrey R. Infante
Affiliations:
Janssen R&D,Spring House,United States
,
Jenna D. Goldberg
Affiliations:
Janssen R&D,Raritan,United States
,
Arnob Banerjee
Affiliations:
Janssen R&D,Spring House,United States
,
Alfred L. Garfall
Affiliations:
Perelman School of Medicine and Abramson Cancer Center,Philadelphia,United States
Niels W.C.J. van de Donk
Affiliations:
Amsterdam University Medical Center, Location VU University Medical Center,Amsterdam,Netherlands
EHA Library. Mateos M. 06/12/20; 295026; S206
Dr. Maria-Victoria Mateos
Dr. Maria-Victoria Mateos
Contributions
Abstract

Abstract: S206

Type: Oral Presentation

Presentation during EHA25: All oral abstract presentations will be made available on the on-demand Virtual Congress platform as of Friday, June 12 at 08:30 CEST and will be accessible until October 15, 2020.

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

Presentation during EHA25: All oral abstract presentations will be made available on the on-demand Virtual Congress platform as of Friday, June 12 at 08:30 CEST and will be accessible until October 15, 2020.

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

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