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TALQUETAMAB, A G PROTEIN-COUPLED RECEPTOR FAMILY C GROUP 5 MEMBER D X CD3 BISPECIFIC ANTIBODY, IN RELAPSED/REFRACTORY MULTIPLE MYELOMA: UPDATED EFFICACY AND SAFETY RESULTS FROM MONUMENTAL-1
Author(s): ,
Monique C. Minnema
Affiliations:
University Medical Center Utrecht,Utrecht,Pays-bas;University Medical Center Utrecht,Utrecht,Niederlande;University Medical Center Utrecht,Utrecht,Paesi Bassi;University Medical Center Utrecht,Utrecht,Netherland;University Medical Center Utrecht,Utrecht,Países Bajos;University Medical Center Utrecht,Utrecht,Nederland;University Medical Center Utrecht,Utrecht,Holanda;University Medical Center Utrec
,
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;
,
Jesus G. Berdeja
Affiliations:
Sarah Cannon Research Institute and Tennessee Oncology,Nashville, TN,États-unis;Sarah Cannon Research Institute and Tennessee Oncology,Nashville, TN,Vereinigte Staaten;Sarah Cannon Research Institute and Tennessee Oncology,Nashville, TN,Stati Uniti;Sarah Cannon Research Institute and Tennessee Oncology,Nashville, TN,United States;Sarah Cannon Research Institute and Tennessee Oncology,Nashville, TN
,
Albert Oriol
Affiliations:
Institut Català d'Oncologia and Institut Josep Carreras, Hospital Germans Trias i Pujol, Badalona,Barcelona,Espagne;Institut Català d'Oncologia and Institut Josep Carreras, Hospital Germans Trias i Pujol, Badalona,Barcelona,Spanien;Institut Català d'Oncologia and Institut Josep Carreras, Hospital Germans Trias i Pujol, Badalona,Barcelona,Spagna;Institut Català d'Oncologia and Institut Josep Carrer
,
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
,
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 de Navarr
,
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
,
María-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
,
Luciano J. Costa
Affiliations:
University of Alabama at Birmingham,Birmingham, AL,États-unis;University of Alabama at Birmingham,Birmingham, AL,Vereinigte Staaten;University of Alabama at Birmingham,Birmingham, AL,Stati Uniti;University of Alabama at Birmingham,Birmingham, AL,United States;University of Alabama at Birmingham,Birmingham, AL,Estados Unidos;University of Alabama at Birmingham,Birmingham, AL,Verenigde Staten;Univer
,
Jo Caers
Affiliations:
University of Liège,Liège,Belgique;University of Liège,Liège,Belgien;University of Liège,Liège,Belgio;University of Liège,Liège,Belgium;University of Liège,Liège,Bélgica;University of Liège,Liège,België;University of Liège,Liège,Bélgica;University of Liège,Liège,Belgium;University of Liège,Liège,Belgien
,
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
,
Joanne Ma
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
,
Shiyi Yang
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
,
Brandi W. Hilder
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
,
Jaszianne Tolbert
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
,
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
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: 05/26/22) EHA Library. C. Minnema M. 06/11/22; 357046; S182
Monique C. Minnema
Monique C. Minnema
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: S182

Type: Oral Presentation

Session title: Relapsed/refractory myeloma: Bispecific antibodies

Background
G protein-coupled receptor family C group 5 member D (GPRC5D) is a promising therapeutic target for multiple myeloma (MM) immunotherapy. GPRC5D has limited expression in healthy human tissue but is highly expressed on malignant plasma cells. Talquetamab (JNJ-64407564) is a first-in-class, GPRC5D x CD3 bispecific IgG4 antibody that induces T cell–activated lysis of GPRC5D+ MM. MonumenTAL-1 is a phase 1 trial evaluating the safety and preliminary efficacy of talquetamab in patients with relapsed/refractory MM (RRMM) (NCT03399799).

Aims
We report updated results from MonumenTAL-1 with additional patients and longer follow-up.

Methods
Patients with RRMM or who were intolerant to standard therapies were eligible; prior treatment with B-cell maturation antigen-directed therapies was allowed. The primary objectives were to identify the recommended phase 2 doses (RP2Ds) (part 1) and assess the safety and tolerability of talquetamab at the RP2Ds (part 2). Based on the collective safety, preliminary efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) data, 2 RP2Ds of talquetamab were identified: 405 μg/kg SC QW (n=30) and 800 μg/kg SC Q2W (n=44). To mitigate severe cytokine release syndrome (CRS), step-up dosing was used. Administration of required premedications were limited to step-up doses and the first full dose of talquetamab. Adverse events (AEs) were graded by CTCAE v4.03, and CRS events were graded per Lee et al 2014 criteria. Responses were assessed by the investigators as per International Myeloma Working Group criteria.

Results
As of Jan 17, 2022, patients in the 405 μg/kg /800 μg/kg groups, respectively, received a median of 6/5 prior lines of therapy, 100%/98% were triple-class (TC) exposed, and 77%/75% were TC refractory, and median follow-up (range) was 11.7 (1.0–21.2)/4.2 (0.7–13.7) months. AEs were mostly grade 1 or 2, and cytopenias and CRS were the most commonly reported AEs. Cytopenias, including neutropenia (67%/36%; grade 3/4: 53%/23%), were mostly limited to step-up and cycle 1–2 doses, reversible, and generally resolved within 1 week. CRS (77%/80%; grade 3: 3%/0%) were mostly reported during step-up dosing. Infections were reported in 47%/34% (grade 3/4: 7%/9%) of patients. 83%/75% of patients reported skin-related and nail disorder AEs (most commonly skin exfoliation: 37%/39% [all grade 1 and 2]). Dysgeusia (63%/57%) was generally mild and managed with dose adjustments. Response-evaluable patients had overall response rates of 70% (21/30 patients)/64% (28/44 patients). Very good partial response or better rates were 57%/52%, and median time to first confirmed response (range) was 0.9 (0.2–3.8)/1.2 (0.3–6.8) months. Median duration of response will be reported. No deaths from drug-related AEs were reported. Both RP2Ds showed comparable PK and PD profiles.

Conclusion
Both RP2Ds of talquetamab appear tolerable with comparable safety and PK profiles. Talquetamab demonstrated highly promising efficacy as a novel, first-in-class therapy for heavily pretreated patients with RRMM.

Keyword(s): Bispecific, Immunotherapy, Multiple myeloma, T cell activation



© 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: S182

Type: Oral Presentation

Session title: Relapsed/refractory myeloma: Bispecific antibodies

Background
G protein-coupled receptor family C group 5 member D (GPRC5D) is a promising therapeutic target for multiple myeloma (MM) immunotherapy. GPRC5D has limited expression in healthy human tissue but is highly expressed on malignant plasma cells. Talquetamab (JNJ-64407564) is a first-in-class, GPRC5D x CD3 bispecific IgG4 antibody that induces T cell–activated lysis of GPRC5D+ MM. MonumenTAL-1 is a phase 1 trial evaluating the safety and preliminary efficacy of talquetamab in patients with relapsed/refractory MM (RRMM) (NCT03399799).

Aims
We report updated results from MonumenTAL-1 with additional patients and longer follow-up.

Methods
Patients with RRMM or who were intolerant to standard therapies were eligible; prior treatment with B-cell maturation antigen-directed therapies was allowed. The primary objectives were to identify the recommended phase 2 doses (RP2Ds) (part 1) and assess the safety and tolerability of talquetamab at the RP2Ds (part 2). Based on the collective safety, preliminary efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) data, 2 RP2Ds of talquetamab were identified: 405 μg/kg SC QW (n=30) and 800 μg/kg SC Q2W (n=44). To mitigate severe cytokine release syndrome (CRS), step-up dosing was used. Administration of required premedications were limited to step-up doses and the first full dose of talquetamab. Adverse events (AEs) were graded by CTCAE v4.03, and CRS events were graded per Lee et al 2014 criteria. Responses were assessed by the investigators as per International Myeloma Working Group criteria.

Results
As of Jan 17, 2022, patients in the 405 μg/kg /800 μg/kg groups, respectively, received a median of 6/5 prior lines of therapy, 100%/98% were triple-class (TC) exposed, and 77%/75% were TC refractory, and median follow-up (range) was 11.7 (1.0–21.2)/4.2 (0.7–13.7) months. AEs were mostly grade 1 or 2, and cytopenias and CRS were the most commonly reported AEs. Cytopenias, including neutropenia (67%/36%; grade 3/4: 53%/23%), were mostly limited to step-up and cycle 1–2 doses, reversible, and generally resolved within 1 week. CRS (77%/80%; grade 3: 3%/0%) were mostly reported during step-up dosing. Infections were reported in 47%/34% (grade 3/4: 7%/9%) of patients. 83%/75% of patients reported skin-related and nail disorder AEs (most commonly skin exfoliation: 37%/39% [all grade 1 and 2]). Dysgeusia (63%/57%) was generally mild and managed with dose adjustments. Response-evaluable patients had overall response rates of 70% (21/30 patients)/64% (28/44 patients). Very good partial response or better rates were 57%/52%, and median time to first confirmed response (range) was 0.9 (0.2–3.8)/1.2 (0.3–6.8) months. Median duration of response will be reported. No deaths from drug-related AEs were reported. Both RP2Ds showed comparable PK and PD profiles.

Conclusion
Both RP2Ds of talquetamab appear tolerable with comparable safety and PK profiles. Talquetamab demonstrated highly promising efficacy as a novel, first-in-class therapy for heavily pretreated patients with RRMM.

Keyword(s): Bispecific, Immunotherapy, Multiple myeloma, T cell activation



© 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.

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