EHA Library - The official digital education library of European Hematology Association (EHA)

TECLISTAMAB IN COMBINATION WITH DARATUMUMAB, A NOVEL, IMMUNOTHERAPY-BASED APPROACH FOR THE TREATMENT OF RELAPSED/REFRACTORY MULTIPLE MYELOMA: UPDATED PHASE 1B RESULTS
Author(s): ,
Paula Rodriguez Otero
Affiliations:
University of Navarra,Navarra,Espagne;University of Navarra,Navarra,Spanien;University of Navarra,Navarra,Spagna;University of Navarra,Navarra,Spain;University of Navarra,Navarra,España;University of Navarra,Navarra,Spanje;University of Navarra,Navarra,Espanha;University of Navarra,Navarra,Испания;University of Navarra,Navarra,Spanien
,
Anita D'Souza
Affiliations:
Medical College of Wisconsin,Milwaukee, WI,États-unis;Medical College of Wisconsin,Milwaukee, WI,Vereinigte Staaten;Medical College of Wisconsin,Milwaukee, WI,Stati Uniti;Medical College of Wisconsin,Milwaukee, WI,United States;Medical College of Wisconsin,Milwaukee, WI,Estados Unidos;Medical College of Wisconsin,Milwaukee, WI,Verenigde Staten;Medical College of Wisconsin,Milwaukee, WI,Estados Uni
,
Donna Reece
Affiliations:
Princess Margaret Cancer Centre,Toronto, ON,Canada;Princess Margaret Cancer Centre,Toronto, ON,Kanada;Princess Margaret Cancer Centre,Toronto, ON,Canada;Princess Margaret Cancer Centre,Toronto, ON,Canada;Princess Margaret Cancer Centre,Toronto, ON,Canadá;Princess Margaret Cancer Centre,Toronto, ON,Canada;Princess Margaret Cancer Centre,Toronto, ON,Canadá;Princess Margaret Cancer Centre,Toronto, ON
,
Niels WCJ van de Donk
Affiliations:
Amsterdam University Medical Center, Vrije Universiteit Amsterdam,Amsterdam,Pays-bas;Amsterdam University Medical Center, Vrije Universiteit Amsterdam,Amsterdam,Niederlande;Amsterdam University Medical Center, Vrije Universiteit Amsterdam,Amsterdam,Paesi Bassi;Amsterdam University Medical Center, Vrije Universiteit Amsterdam,Amsterdam,Netherland;Amsterdam University Medical Center, Vrije Universit
,
Ajai Chari
Affiliations:
Mount Sinai School of Medicine,New York, NY,États-unis;Mount Sinai School of Medicine,New York, NY,Vereinigte Staaten;Mount Sinai School of Medicine,New York, NY,Stati Uniti;Mount Sinai School of Medicine,New York, NY,United States;Mount Sinai School of Medicine,New York, NY,Estados Unidos;Mount Sinai School of Medicine,New York, NY,Verenigde Staten;Mount Sinai School of Medicine,New York, NY,Esta
,
Amrita Krishnan
Affiliations:
City of Hope Comprehensive Cancer Center,Duarte, CA,États-unis;City of Hope Comprehensive Cancer Center,Duarte, CA,Vereinigte Staaten;City of Hope Comprehensive Cancer Center,Duarte, CA,Stati Uniti;City of Hope Comprehensive Cancer Center,Duarte, CA,United States;City of Hope Comprehensive Cancer Center,Duarte, CA,Estados Unidos;City of Hope Comprehensive Cancer Center,Duarte, CA,Verenigde Staten;
,
Thomas Martin
Affiliations:
UCSF Helen Diller Family Comprehensive Cancer Center,San Francisco, CA,États-unis;UCSF Helen Diller Family Comprehensive Cancer Center,San Francisco, CA,Vereinigte Staaten;UCSF Helen Diller Family Comprehensive Cancer Center,San Francisco, CA,Stati Uniti;UCSF Helen Diller Family Comprehensive Cancer Center,San Francisco, CA,United States;UCSF Helen Diller Family Comprehensive Cancer Center,San Fra
,
Maria Victoria Mateos
Affiliations:
University Hospital of Salamanca/IBSAL/CIC/CIBERONC,Salamanca,Espagne;University Hospital of Salamanca/IBSAL/CIC/CIBERONC,Salamanca,Spanien;University Hospital of Salamanca/IBSAL/CIC/CIBERONC,Salamanca,Spagna;University Hospital of Salamanca/IBSAL/CIC/CIBERONC,Salamanca,Spain;University Hospital of Salamanca/IBSAL/CIC/CIBERONC,Salamanca,España;University Hospital of Salamanca/IBSAL/CIC/CIBERONC,Sa
,
Daniel Morillo
Affiliations:
Hospital Universitario Fundación Jiménez Díaz,Madrid,Espagne;Hospital Universitario Fundación Jiménez Díaz,Madrid,Spanien;Hospital Universitario Fundación Jiménez Díaz,Madrid,Spagna;Hospital Universitario Fundación Jiménez Díaz,Madrid,Spain;Hospital Universitario Fundación Jiménez Díaz,Madrid,España;Hospital Universitario Fundación Jiménez Díaz,Madrid,Spanje;Hospital Universitario Fundación Jiméne
,
David Hurd
Affiliations:
Comprehensive Cancer Center of Wake Forest Baptist Health,Winston-Salem, NC,États-unis;Comprehensive Cancer Center of Wake Forest Baptist Health,Winston-Salem, NC,Vereinigte Staaten;Comprehensive Cancer Center of Wake Forest Baptist Health,Winston-Salem, NC,Stati Uniti;Comprehensive Cancer Center of Wake Forest Baptist Health,Winston-Salem, NC,United States;Comprehensive Cancer Center of Wake Fore
,
Laura Rosinol
Affiliations:
Hospital Clínic, Institut d'investigacions Biomèdiques August Pi i Sunyer,Barcelona,Espagne;Hospital Clínic, Institut d'investigacions Biomèdiques August Pi i Sunyer,Barcelona,Spanien;Hospital Clínic, Institut d'investigacions Biomèdiques August Pi i Sunyer,Barcelona,Spagna;Hospital Clínic, Institut d'investigacions Biomèdiques August Pi i Sunyer,Barcelona,Spain;Hospital Clínic, Institut d'investi
,
Anna Sureda Balari
Affiliations:
Institut Català d'Oncologia – Hospitalet, IDIBELL, University of Barcelona, Barcelona,Espagne;Institut Català d'Oncologia – Hospitalet, IDIBELL, University of Barcelona, Barcelona,Spanien;Institut Català d'Oncologia – Hospitalet, IDIBELL, University of Barcelona, Barcelona,Spagna;Institut Català d'Oncologia – Hospitalet, IDIBELL, University of Barcelona, Barcelona,Spain;Institut Català d'Oncologia
,
Ralph Wäsch
Affiliations:
Freiburg University Medical Center,Freiburg,Allemagne;Freiburg University Medical Center,Freiburg,Deutschland;Freiburg University Medical Center,Freiburg,Germania;Freiburg University Medical Center,Freiburg,Germany;Freiburg University Medical Center,Freiburg,Alemania;Freiburg University Medical Center,Freiburg,Duitsland;Freiburg University Medical Center,Freiburg,Alemanha;Freiburg University Medic
,
Deeksha Vishwamitra
Affiliations:
Janssen Research and Development,Spring House, PA,États-unis;Janssen Research and Development,Spring House, PA,Vereinigte Staaten;Janssen Research and Development,Spring House, PA,Stati Uniti;Janssen Research and Development,Spring House, PA,United States;Janssen Research and Development,Spring House, PA,Estados Unidos;Janssen Research and Development,Spring House, PA,Verenigde Staten;Janssen Rese
,
Shun Xin Wang Lin
Affiliations:
Janssen Research and Development,Spring House, PA,États-unis;Janssen Research and Development,Spring House, PA,Vereinigte Staaten;Janssen Research and Development,Spring House, PA,Stati Uniti;Janssen Research and Development,Spring House, PA,United States;Janssen Research and Development,Spring House, PA,Estados Unidos;Janssen Research and Development,Spring House, PA,Verenigde Staten;Janssen Rese
,
Thomas Prior
Affiliations:
Janssen Research and Development,Spring House, PA,États-unis;Janssen Research and Development,Spring House, PA,Vereinigte Staaten;Janssen Research and Development,Spring House, PA,Stati Uniti;Janssen Research and Development,Spring House, PA,United States;Janssen Research and Development,Spring House, PA,Estados Unidos;Janssen Research and Development,Spring House, PA,Verenigde Staten;Janssen Rese
,
Lien Vandenberk
Affiliations:
Janssen Research & Development,Antwerp,Belgique;Janssen Research & Development,Antwerp,Belgien;Janssen Research & Development,Antwerp,Belgio;Janssen Research & Development,Antwerp,Belgium;Janssen Research & Development,Antwerp,Bélgica;Janssen Research & Development,Antwerp,België;Janssen Research & Development,Antwerp,Bélgica;Janssen Research
,
Marie-Anne Damiette Smit
Affiliations:
Janssen Research & Development,Los Angeles, CA,États-unis;Janssen Research & Development,Los Angeles, CA,Vereinigte Staaten;Janssen Research & Development,Los Angeles, CA,Stati Uniti;Janssen Research & Development,Los Angeles, CA,United States;Janssen Research & Development,Los Angeles, CA,Estados Unidos;Janssen Research & Development,Los Angeles, CA
,
Albert Oriol
Affiliations:
Hospital Germans Trias i Pujol, Badalona,Barcelona,Espagne;Hospital Germans Trias i Pujol, Badalona,Barcelona,Spanien;Hospital Germans Trias i Pujol, Badalona,Barcelona,Spagna;Hospital Germans Trias i Pujol, Badalona,Barcelona,Spain;Hospital Germans Trias i Pujol, Badalona,Barcelona,España;Hospital Germans Trias i Pujol, Badalona,Barcelona,Spanje;Hospital Germans Trias i Pujol, Badalona,Barcelona,
Bhagirathbhai Dholaria
Affiliations:
Vanderbilt University Medical Center,Nashville, TN,États-unis;Vanderbilt University Medical Center,Nashville, TN,Vereinigte Staaten;Vanderbilt University Medical Center,Nashville, TN,Stati Uniti;Vanderbilt University Medical Center,Nashville, TN,United States;Vanderbilt University Medical Center,Nashville, TN,Estados Unidos;Vanderbilt University Medical Center,Nashville, TN,Verenigde Staten;Vander
(Abstract release date: 05/26/22) EHA Library. Rodriguez Otero P. 06/12/22; 357052; S188
Dr. Paula Rodriguez Otero
Dr. Paula Rodriguez Otero
Contributions
Abstract
Presentation during EHA2022: All Oral presentations will be presented between Friday, June 10 and Sunday, June 12 and will be accessible for on-demand viewing from Monday, June 20 until Monday, August 15, 2022 on the Congress platform.

Abstract: S188

Type: Oral Presentation

Session title: Relapsed/refractory myeloma: BCMA-directed therapies

Background
Teclistamab (JNJ-64007957) is a B-cell maturation antigen (BCMA) × CD3 T-cell redirecting bispecific antibody currently under investigation in patients with relapsed/refractory multiple myeloma (RRMM). Daratumumab is a CD38-targeting monoclonal antibody with direct on-tumor and immunomodulatory mechanisms of action. The preliminary results from the phase 1b multicohort TRIMM-2 study showed tolerable safety with no overlapping toxicities, and encouraging efficacy, supporting the combination of teclistamab with daratumumab for the treatment of RRMM.

Aims
We report updated results from the TRIMM-2 study with additional patients and longer follow-up.

Methods
Eligible patients were ≥18 years of age with a MM diagnosis and previously treated with ≥3 prior lines of therapy (including a proteosome inhibitor [PI] and immunomodulatory drug [IMiD]) or were double-refractory to a PI and IMiD. Patients who had received anti-CD38 therapy ≤90 days prior were excluded. Written informed consent was obtained from all eligible patients. Patients received subcutaneous (SC) daratumumab 1800 mg per approved schedule and teclistamab SC 1.5–3 mg/kg once weekly or every 2 weeks. Primary objectives of the study were to identify the recommended phase 2 dose for the teclistamab and daratumumab combination and to assess safety of the combination. Responses were assessed by IMWG criteria. Adverse events (AEs) were graded per CTCAE v5.0, except for cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS), which were graded per ASTCT guidelines.

Results
At the Jan 13, 2022 data cutoff, the median follow-up was 7.2 months (range 0.1–16.6). Among the safety population (N=46), 52% were females, and the median age was 67 years (range 50–79). Patients received a median of 6 prior lines of therapy (range 2–17); 74% of patients were triple-class exposed; 63% were penta-drug exposed, and 15% were anti-BCMA exposed. Overall, 91% of patients had ≥1 AE of any grade; 78% had grade 3/4 AEs. The most common AE was CRS (61%; all grade 1/2); median time to onset was 2 days and median duration was 2 days. Other AEs included neutropenia (54%; grade 3/4 50%), anemia (46%; grade 3/4 28%), thrombocytopenia (33%; grade 3/4 28%), and diarrhea (33%; grade 3/4 2%). Infections occurred in 29 patients (63%; grade 3/4 28%). One patient had grade 1 ICANS that was fully resolved. Among 37 response-evaluable patients, the overall response rate was 78% (29/37); 27 patients (73%) had very good partial response (VGPR) or better (Table). While the median duration of response was not reached, median time to first response across dosing cohorts was 1.0 month (range 0.9–2.8). Upregulation of CD38+/CD8+ T cells and proinflammatory cytokines was observed after teclistamab dosing in combination with daratumumab, supporting potential synergy of the combination in patients with prior anti-CD38 exposure. Updated results will be presented.

Conclusion
Teclistamab in combination with daratumumab is a novel immunotherapy approach that may yield improved clinical efficacy in heavily pretreated patients with RRMM.

Keyword(s): B-cell maturation antigen, Bispecific, Immunotherapy, Multiple myeloma



© 2022 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2022 ASCO Annual Meeting. All rights reserved.
Presentation during EHA2022: All Oral presentations will be presented between Friday, June 10 and Sunday, June 12 and will be accessible for on-demand viewing from Monday, June 20 until Monday, August 15, 2022 on the Congress platform.

Abstract: S188

Type: Oral Presentation

Session title: Relapsed/refractory myeloma: BCMA-directed therapies

Background
Teclistamab (JNJ-64007957) is a B-cell maturation antigen (BCMA) × CD3 T-cell redirecting bispecific antibody currently under investigation in patients with relapsed/refractory multiple myeloma (RRMM). Daratumumab is a CD38-targeting monoclonal antibody with direct on-tumor and immunomodulatory mechanisms of action. The preliminary results from the phase 1b multicohort TRIMM-2 study showed tolerable safety with no overlapping toxicities, and encouraging efficacy, supporting the combination of teclistamab with daratumumab for the treatment of RRMM.

Aims
We report updated results from the TRIMM-2 study with additional patients and longer follow-up.

Methods
Eligible patients were ≥18 years of age with a MM diagnosis and previously treated with ≥3 prior lines of therapy (including a proteosome inhibitor [PI] and immunomodulatory drug [IMiD]) or were double-refractory to a PI and IMiD. Patients who had received anti-CD38 therapy ≤90 days prior were excluded. Written informed consent was obtained from all eligible patients. Patients received subcutaneous (SC) daratumumab 1800 mg per approved schedule and teclistamab SC 1.5–3 mg/kg once weekly or every 2 weeks. Primary objectives of the study were to identify the recommended phase 2 dose for the teclistamab and daratumumab combination and to assess safety of the combination. Responses were assessed by IMWG criteria. Adverse events (AEs) were graded per CTCAE v5.0, except for cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS), which were graded per ASTCT guidelines.

Results
At the Jan 13, 2022 data cutoff, the median follow-up was 7.2 months (range 0.1–16.6). Among the safety population (N=46), 52% were females, and the median age was 67 years (range 50–79). Patients received a median of 6 prior lines of therapy (range 2–17); 74% of patients were triple-class exposed; 63% were penta-drug exposed, and 15% were anti-BCMA exposed. Overall, 91% of patients had ≥1 AE of any grade; 78% had grade 3/4 AEs. The most common AE was CRS (61%; all grade 1/2); median time to onset was 2 days and median duration was 2 days. Other AEs included neutropenia (54%; grade 3/4 50%), anemia (46%; grade 3/4 28%), thrombocytopenia (33%; grade 3/4 28%), and diarrhea (33%; grade 3/4 2%). Infections occurred in 29 patients (63%; grade 3/4 28%). One patient had grade 1 ICANS that was fully resolved. Among 37 response-evaluable patients, the overall response rate was 78% (29/37); 27 patients (73%) had very good partial response (VGPR) or better (Table). While the median duration of response was not reached, median time to first response across dosing cohorts was 1.0 month (range 0.9–2.8). Upregulation of CD38+/CD8+ T cells and proinflammatory cytokines was observed after teclistamab dosing in combination with daratumumab, supporting potential synergy of the combination in patients with prior anti-CD38 exposure. Updated results will be presented.

Conclusion
Teclistamab in combination with daratumumab is a novel immunotherapy approach that may yield improved clinical efficacy in heavily pretreated patients with RRMM.

Keyword(s): B-cell maturation antigen, Bispecific, Immunotherapy, Multiple myeloma



© 2022 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2022 ASCO Annual Meeting. All rights reserved.

By clicking “Accept Terms & all Cookies” or by continuing to browse, you agree to the storing of third-party cookies on your device to enhance your user experience and agree to the user terms and conditions of this learning management system (LMS).

Cookie Settings
Accept Terms & all Cookies