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NOVEL COMBINATION IMMUNOTHERAPY FOR THE TREATMENT OF RELAPSED/REFRACTORY MULTIPLE MYELOMA: UPDATED PHASE 1B RESULTS FOR TALQUETAMAB (A GPRC5D X CD3 BISPECIFIC ANTIBODY) IN COMBINATION WITH DARATUMUMAB
Author(s): ,
Niels WJC 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
,
Nizar Bahlis
Affiliations:
Arnie Charbonneau Cancer Institute, University of Calgary,Calgary, AB,Canada;Arnie Charbonneau Cancer Institute, University of Calgary,Calgary, AB,Kanada;Arnie Charbonneau Cancer Institute, University of Calgary,Calgary, AB,Canada;Arnie Charbonneau Cancer Institute, University of Calgary,Calgary, AB,Canada;Arnie Charbonneau Cancer Institute, University of Calgary,Calgary, AB,Canadá;Arnie Charbonne
,
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
,
Katja Weisel
Affiliations:
University Medical Center Hamburg-Eppendorf,Hamburg,Allemagne;University Medical Center Hamburg-Eppendorf,Hamburg,Deutschland;University Medical Center Hamburg-Eppendorf,Hamburg,Germania;University Medical Center Hamburg-Eppendorf,Hamburg,Germany;University Medical Center Hamburg-Eppendorf,Hamburg,Alemania;University Medical Center Hamburg-Eppendorf,Hamburg,Duitsland;University Medical Center Hamb
,
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
,
Alfred L Garfall
Affiliations:
Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA,États-unis;Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA,Vereinigte Staaten;Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA,Stati Uniti;Abramson Cancer Center, Perelman School of Medicine, University
,
Hartmut Goldschmidt
Affiliations:
University Hospital Heidelberg, Internal Medicine and National Center for Tumor Diseases,Heidelberg,Allemagne;University Hospital Heidelberg, Internal Medicine and National Center for Tumor Diseases,Heidelberg,Deutschland;University Hospital Heidelberg, Internal Medicine and National Center for Tumor Diseases,Heidelberg,Germania;University Hospital Heidelberg, Internal Medicine and National Center
,
Thomas G Martin
Affiliations:
University of California, San Francisco,San Francisco, CA ,États-unis;University of California, San Francisco,San Francisco, CA ,Vereinigte Staaten;University of California, San Francisco,San Francisco, CA ,Stati Uniti;University of California, San Francisco,San Francisco, CA ,United States;University of California, San Francisco,San Francisco, CA ,Estados Unidos;University of California, San Fran
,
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
,
Donna Ellen 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
,
David Hurd
Affiliations:
Section on Hematology and Oncology, Department of Internal Medicine, Comprehensive Cancer Center of Wake Forest University,Winston-Salem, NC,États-unis;Section on Hematology and Oncology, Department of Internal Medicine, Comprehensive Cancer Center of Wake Forest University,Winston-Salem, NC,Vereinigte Staaten;Section on Hematology and Oncology, Department of Internal Medicine, Comprehensive Cance
,
Paula Rodríguez-Otero
Affiliations:
Clínica Universidad de Navarra, Navarra,Espagne;Clínica Universidad de Navarra, Navarra,Spanien;Clínica Universidad de Navarra, Navarra,Spagna;Clínica Universidad de Navarra, Navarra,Spain;Clínica Universidad de Navarra, Navarra,España;Clínica Universidad de Navarra, Navarra,Spanje;Clínica Universidad de Navarra, Navarra,Espanha;Clínica Universidad de Navarra, Navarra,Испания;Clínica Universidad d
,
Manisha Bhutani
Affiliations:
Levine Cancer Institute/Atrium Health,Charlotte, NC,États-unis;Levine Cancer Institute/Atrium Health,Charlotte, NC,Vereinigte Staaten;Levine Cancer Institute/Atrium Health,Charlotte, NC,Stati Uniti;Levine Cancer Institute/Atrium Health,Charlotte, NC,United States;Levine Cancer Institute/Atrium Health,Charlotte, NC,Estados Unidos;Levine Cancer Institute/Atrium Health,Charlotte, NC,Verenigde Staten;
,
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
,
Albert Oriol
Affiliations:
Institut Català d'Oncologia and Institut Josep Carreras and Hospital Germans Trias i Pujol, Badalona,Barcelona,Espagne;Institut Català d'Oncologia and Institut Josep Carreras and Hospital Germans Trias i Pujol, Badalona,Barcelona,Spanien;Institut Català d'Oncologia and Institut Josep Carreras and Hospital Germans Trias i Pujol, Badalona,Barcelona,Spagna;Institut Català d'Oncologia and Institut Jos
,
Elham Askari
Affiliations:
Department of Hematology, Fundacion Jimenez Diaz University Hospital,Madrid,Espagne;Department of Hematology, Fundacion Jimenez Diaz University Hospital,Madrid,Spanien;Department of Hematology, Fundacion Jimenez Diaz University Hospital,Madrid,Spagna;Department of Hematology, Fundacion Jimenez Diaz University Hospital,Madrid,Spain;Department of Hematology, Fundacion Jimenez Diaz University Hospita
,
Jesús F San-Miguel
Affiliations:
Clínica Universidad de Navarra, CCUN, CIMA, CIBERONC, IDISNA,Pamplona,Espagne;Clínica Universidad de Navarra, CCUN, CIMA, CIBERONC, IDISNA,Pamplona,Spanien;Clínica Universidad de Navarra, CCUN, CIMA, CIBERONC, IDISNA,Pamplona,Spagna;Clínica Universidad de Navarra, CCUN, CIMA, CIBERONC, IDISNA,Pamplona,Spain;Clínica Universidad de Navarra, CCUN, CIMA, CIBERONC, IDISNA,Pamplona,España;Clínica Univer
,
K Martin Kortüm
Affiliations:
Medizinische Klinik II, Universitätsklinikum Würzburg,Würzburg,Allemagne;Medizinische Klinik II, Universitätsklinikum Würzburg,Würzburg,Deutschland;Medizinische Klinik II, Universitätsklinikum Würzburg,Würzburg,Germania;Medizinische Klinik II, Universitätsklinikum Würzburg,Würzburg,Germany;Medizinische Klinik II, Universitätsklinikum Würzburg,Würzburg,Alemania;Medizinische Klinik II, Universitätsk
,
Deeksha Vishwamitra
Affiliations:
Janssen Research & Development,Spring House, PA,États-unis;Janssen Research & Development,Spring House, PA,Vereinigte Staaten;Janssen Research & Development,Spring House, PA,Stati Uniti;Janssen Research & Development,Spring House, PA,United States;Janssen Research & Development,Spring House, PA,Estados Unidos;Janssen Research & Development,Spring Hou
,
Shun Xin Wang Lin
Affiliations:
Janssen Research & Development,Spring House, PA,États-unis;Janssen Research & Development,Spring House, PA,Vereinigte Staaten;Janssen Research & Development,Spring House, PA,Stati Uniti;Janssen Research & Development,Spring House, PA,United States;Janssen Research & Development,Spring House, PA,Estados Unidos;Janssen Research & Development,Spring Hou
,
Thomas J Prior
Affiliations:
Janssen Research & Development,Spring House, PA,États-unis;Janssen Research & Development,Spring House, PA,Vereinigte Staaten;Janssen Research & Development,Spring House, PA,Stati Uniti;Janssen Research & Development,Spring House, PA,United States;Janssen Research & Development,Spring House, PA,Estados Unidos;Janssen Research & Development,Spring Hou
,
Lien Vandenberk
Affiliations:
Janssen Research & Development,Beerse,Belgique;Janssen Research & Development,Beerse,Belgien;Janssen Research & Development,Beerse,Belgio;Janssen Research & Development,Beerse,Belgium;Janssen Research & Development,Beerse,Bélgica;Janssen Research & Development,Beerse,België;Janssen Research & Development,Beerse,Bélgica;Janssen Research &a
,
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
,
Jenna D Goldberg
Affiliations:
Janssen Research & Development,Raritan, NJ,États-unis;Janssen Research & Development,Raritan, NJ,Vereinigte Staaten;Janssen Research & Development,Raritan, NJ,Stati Uniti;Janssen Research & Development,Raritan, NJ,United States;Janssen Research & Development,Raritan, NJ,Estados Unidos;Janssen Research & Development,Raritan, NJ,Verenigde Staten;Jansse
,
Ralph Wäsch
Affiliations:
University of Freiburg,Freiburg,Allemagne;University of Freiburg,Freiburg,Deutschland;University of Freiburg,Freiburg,Germania;University of Freiburg,Freiburg,Germany;University of Freiburg,Freiburg,Alemania;University of Freiburg,Freiburg,Duitsland;University of Freiburg,Freiburg,Alemanha;University of Freiburg,Freiburg,Германия;University of Freiburg,Freiburg,Tyskland
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
(Abstract release date: 05/12/22) EHA Library. WJC van de Donk N. 06/11/22; 357047; S183
Niels WJC van de Donk
Niels WJC van de Donk
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: S183

Type: Oral Presentation

Session title: Relapsed/refractory myeloma: Bispecific antibodies

Background

Talquetamab (tal; JNJ-64407564) is a first-in-class, bispecific IgG4 antibody that binds both to G protein-coupled receptor family C group 5 member D (GPRC5D), a receptor highly expressed on malignant plasma cells but with limited expression in healthy tissue, and CD3 to mediate T-cell–activated lysis of GPRC5D+ multiple myeloma (MM) cells. Daratumumab (dara) is an anti-CD38 mAb with direct on-tumor and immunomodulatory actions. Initial clinical results from the phase 1b multicohort TRIMM-2 study identified the recommended phase 2 doses (RP2Ds) of tal as 400 μg/kg weekly or 800 μg/kg Q2W and support the combination of tal + dara for the treatment of RRMM, with manageable safety, no overlapping toxicities, and promising efficacy.

Aims
Here we report updated results for both RP2Ds of tal + dara in TRIMM-2 with additional patients (pts) and longer follow-up.

Methods
Eligible MM pts (aged ≥18 years) had received ≥3 prior lines of therapy (LOT; including a PI and IMiD) or were double refractory to a PI and an IMiD, and could not have received anti-CD38 therapy within 90 days. Pts received dara SC 1800 mg per approved schedule and tal (400 μg/kg weekly or 800 μg/kg Q2W) with step-up dosing. The primary objectives were to identify the RP2D(s) of tal for combination therapy and evaluate safety of the combination. AEs were graded per CTCAE v5.0; cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS) were graded per ASTCT guidelines. Responses were assessed by IMWG criteria.

Results
At data cutoff (Jan 13, 2022, N=46), median follow-up was 4.0 months (range 0.4-16.3), median age was 65 years (range 47-81), and 48% were female. Pts received a median of 5 prior LOT (range 2-16); 83% were triple-class exposed, 61% penta-drug exposed, 37% anti-BCMA non–CAR-T exposed, and 4% anti-BCMA CAR-T exposed. 96% of pts had ≥1 AE (gr 3/4: 67%). The most frequently reported AEs (≥30% across tal + dara cohorts) were CRS (65%; all gr 1/2; median time to onset: 2 days; median duration: 2 days), dysgeusia (57%), thrombocytopenia (35%; gr 3/4: 20%), anemia (39%; gr 3/4: 20%), and dry mouth (44%). Infections occurred in 50% of pts (gr 3/4: 13%). Skin disorders were reported in 72% of pts (gr 3/4: 11%): skin exfoliation in 26% (all gr 1/2) and nail disorders in 11% (all gr 1/2). Two ICANS events were reported in the 800 Q2W group (both gr 1 and resolved within 1 day). 3 pts discontinued due to AEs. Response rates were consistent across both RP2Ds supporting their equivalence (Table). Median time to first response across dosing cohorts was 0.95 months (range 0.9-9.7); median duration of response was not reached. Upregulation of CD38+/CD8+ T cells and proinflammatory cytokines was observed with tal + dara, supporting potential synergy of the combination in pts with prior anti-CD38 exposure. Updated results will be presented.

Conclusion
Longer follow-up with additional patients shows comparable efficacy and safety across both RP2Ds, with no new safety signals, strengthening the benefit-risk profile of tal + dara as a novel immunotherapy-based approach for heavily pretreated pts with RRMM.

Keyword(s): Bispecific, CD38, Multiple myeloma, Safety

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: S183

Type: Oral Presentation

Session title: Relapsed/refractory myeloma: Bispecific antibodies

Background

Talquetamab (tal; JNJ-64407564) is a first-in-class, bispecific IgG4 antibody that binds both to G protein-coupled receptor family C group 5 member D (GPRC5D), a receptor highly expressed on malignant plasma cells but with limited expression in healthy tissue, and CD3 to mediate T-cell–activated lysis of GPRC5D+ multiple myeloma (MM) cells. Daratumumab (dara) is an anti-CD38 mAb with direct on-tumor and immunomodulatory actions. Initial clinical results from the phase 1b multicohort TRIMM-2 study identified the recommended phase 2 doses (RP2Ds) of tal as 400 μg/kg weekly or 800 μg/kg Q2W and support the combination of tal + dara for the treatment of RRMM, with manageable safety, no overlapping toxicities, and promising efficacy.

Aims
Here we report updated results for both RP2Ds of tal + dara in TRIMM-2 with additional patients (pts) and longer follow-up.

Methods
Eligible MM pts (aged ≥18 years) had received ≥3 prior lines of therapy (LOT; including a PI and IMiD) or were double refractory to a PI and an IMiD, and could not have received anti-CD38 therapy within 90 days. Pts received dara SC 1800 mg per approved schedule and tal (400 μg/kg weekly or 800 μg/kg Q2W) with step-up dosing. The primary objectives were to identify the RP2D(s) of tal for combination therapy and evaluate safety of the combination. AEs were graded per CTCAE v5.0; cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS) were graded per ASTCT guidelines. Responses were assessed by IMWG criteria.

Results
At data cutoff (Jan 13, 2022, N=46), median follow-up was 4.0 months (range 0.4-16.3), median age was 65 years (range 47-81), and 48% were female. Pts received a median of 5 prior LOT (range 2-16); 83% were triple-class exposed, 61% penta-drug exposed, 37% anti-BCMA non–CAR-T exposed, and 4% anti-BCMA CAR-T exposed. 96% of pts had ≥1 AE (gr 3/4: 67%). The most frequently reported AEs (≥30% across tal + dara cohorts) were CRS (65%; all gr 1/2; median time to onset: 2 days; median duration: 2 days), dysgeusia (57%), thrombocytopenia (35%; gr 3/4: 20%), anemia (39%; gr 3/4: 20%), and dry mouth (44%). Infections occurred in 50% of pts (gr 3/4: 13%). Skin disorders were reported in 72% of pts (gr 3/4: 11%): skin exfoliation in 26% (all gr 1/2) and nail disorders in 11% (all gr 1/2). Two ICANS events were reported in the 800 Q2W group (both gr 1 and resolved within 1 day). 3 pts discontinued due to AEs. Response rates were consistent across both RP2Ds supporting their equivalence (Table). Median time to first response across dosing cohorts was 0.95 months (range 0.9-9.7); median duration of response was not reached. Upregulation of CD38+/CD8+ T cells and proinflammatory cytokines was observed with tal + dara, supporting potential synergy of the combination in pts with prior anti-CD38 exposure. Updated results will be presented.

Conclusion
Longer follow-up with additional patients shows comparable efficacy and safety across both RP2Ds, with no new safety signals, strengthening the benefit-risk profile of tal + dara as a novel immunotherapy-based approach for heavily pretreated pts with RRMM.

Keyword(s): Bispecific, CD38, Multiple myeloma, Safety

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