TALQUETAMAB, A G PROTEIN-COUPLED RECEPTOR FAMILY C GROUP 5 MEMBER D (GPRC5D) × CD3 BISPECIFIC ANTIBODY, IN RELAPSED/REFRACTORY MULTIPLE MYELOMA: UPDATED RESULTS OF A PHASE 1, FIRST-IN-HUMAN STUDY
Author(s): ,
Amrita Y. Krishnan
Affiliations:
City of Hope Comprehensive Cancer Center,Duarte,United States
,
Jesus G. Berdeja
Affiliations:
Sarah Cannon Research Institute and Tennessee Oncology,Nashville,United States
,
Albert Oriol
Affiliations:
Institut Català d’Oncologia and Institut Josep Carreras Hospital Germans Trias i Pujol,Barcelona,Spain
,
Niels W.C.J. van de Donk
Affiliations:
Amsterdam University Medical Center, VU University Medical Center,Amsterdam,Netherlands
,
Paula Rodríguez-Otero
Affiliations:
Clínica Universidad de Navarra,Navarra,Spain
,
Elham Askari
Affiliations:
Hospital Universitario Fundación Jiménez Díaz,Madrid,Spain
,
Maria-Victoria Mateos
Affiliations:
Hospital Clínico Universitario de Salamanca,Salamanca,Spain
,
Monique C. Minnema
Affiliations:
University Medical Center Utrecht,Utrecht,Netherlands
,
Luciano J. Costa
Affiliations:
University of Alabama at Birmingham,Birmingham,United States
,
Raluca Verona
Affiliations:
Janssen R&D,Spring House,United States
,
Suzette Girgis
Affiliations:
Janssen R&D,Spring House,United States
,
Thomas Prior
Affiliations:
Janssen R&D,Spring House,United States
,
Brandi W. Hilder
Affiliations:
Janssen R&D,Spring House,United States
,
Jeffery Scott Russell
Affiliations:
Janssen R&D,Spring House,United States
,
Jenna D. Goldberg
Affiliations:
Janssen R&D,Raritan,United States
Ajai Chari
Affiliations:
Mount Sinai School of Medicine,New York,United States
EHA Library. Y. Krishnan A. 06/09/21; 324599; S191
Amrita Y. Krishnan
Amrita Y. Krishnan
Contributions
Abstract
Presentation during EHA2021: All Oral presentations will be made available as of Friday, June 11, 2021 (09:00 CEST) and will be accessible for on-demand viewing until August 15, 2021 on the Virtual Congress platform.

Abstract: S191

Type: Oral Presentation

Session title: T cell re-directing therapies in relapsed/refractory multiple myeloma

Background

As patients with multiple myeloma (MM) continue to relapse on current therapies, new immunotherapy targets are needed. G protein-coupled receptor family C group 5 member D (GPRC5D) is an orphan receptor that is expressed on malignant plasma cells in MM. Talquetamab (JNJ-64407564) is a bispecific immunoglobulin G4 antibody that binds to CD3 and the novel target GPRC5D to redirect T cells to kill MM cells.

Aims

To report updated phase 1 results of patients with relapsed/refractory MM treated with talquetamab at the recommended phase 2 dose (RP2D).

Methods

Eligible pts with MM who had relapsed or refractory disease or were intolerant to standard therapies, were administered talquetamab either intravenously (IV; range 0.5–180 μg/kg) or subcutaneously (SC; range 5.0–800 μg/kg) in a weekly or biweekly dosing schedule. The primary objectives of the study were to identify the RP2D (part 1) and to characterize the safety and tolerability of talquetamab at the RP2D (part 2). Adverse events (AEs) were graded by Common Terminology Criteria for Adverse Events (CTCAE) v4.03, and cytokine release syndrome (CRS) was graded per Lee 2014 criteria. Response was assessed per International Myeloma Working Group criteria. All patients provided informed consent.

Results

As of Feb 8, 2021, 174 patients received talquetamab IV (n=102) or SC (n=72). Across parts 1 and 2 of the study, 28 patients were treated at the RP2D, identified as weekly SC 405 μg/kg, with 10.0 and 60.0 μg/kg step-up doses. Patients treated at the RP2D had a median age of 61.5 years (range 46–80 years) and had received a median of 5.5 prior lines of therapy (range 2–14; 100%/79% triple-class/penta-drug exposed; 71%/18% triple-class/penta-drug refractory; 86% refractory to last line of therapy; 21% with prior B-cell maturation antigen–directed therapy). No dose-limiting toxicities occurred at the RP2D in part 1 of the study. The most common AEs at the RP2D were CRS (79%; 4% were grade 3; median time to onset was day after SC dose), neutropenia (64%; 54% were grade 3/4), anemia (57%; 29% were grade 3/4) and dysgeusia (57%; all were grade 1/2). Infections were reported in 32% of patients (4% were grade 3/4) and neurotoxicity reported in 7% (no grade 3/4 events). In all, 75% of patients who received the RP2D had skin-related AEs, none of which were grade 3/4, including 18% with nail disorders. In response-evaluable patients (n=24), the overall response rate at the RP2D was 63%, with 50% reaching very good partial response or better; 9/17 (53%) evaluable triple-class refractory patients and 3/3 (100%) penta-drug refractory patients had a response. The median time to first confirmed response at the RP2D was 1.0 month (range 0.2–3.8). Responses were durable and deepened over time; the median follow-up was 6.2 month [range 2.7–9.7+] for responders at the RP2D. Talquetamab exposure at the RP2D was maintained over the maximum EC target level from an ex vivo cytotoxicity assay. Consistent T cell activation was also observed at the RP2D.

Conclusion

Talquetamab, at the RP2D of weekly 405 μg/kg SC, demonstrated a high clinical response rate and was well-tolerated in patients with relapsed/refractory MM. Based on the pharmacokinetic data, other SC dosing strategies are also being explored. The promising efficacy and safety profile, and the convenience of SC dosing support monotherapy development and combination approaches with this novel agent.

Keyword(s): Immunotherapy, Malignancy, Multiple myeloma

Presentation during EHA2021: All Oral presentations will be made available as of Friday, June 11, 2021 (09:00 CEST) and will be accessible for on-demand viewing until August 15, 2021 on the Virtual Congress platform.

Abstract: S191

Type: Oral Presentation

Session title: T cell re-directing therapies in relapsed/refractory multiple myeloma

Background

As patients with multiple myeloma (MM) continue to relapse on current therapies, new immunotherapy targets are needed. G protein-coupled receptor family C group 5 member D (GPRC5D) is an orphan receptor that is expressed on malignant plasma cells in MM. Talquetamab (JNJ-64407564) is a bispecific immunoglobulin G4 antibody that binds to CD3 and the novel target GPRC5D to redirect T cells to kill MM cells.

Aims

To report updated phase 1 results of patients with relapsed/refractory MM treated with talquetamab at the recommended phase 2 dose (RP2D).

Methods

Eligible pts with MM who had relapsed or refractory disease or were intolerant to standard therapies, were administered talquetamab either intravenously (IV; range 0.5–180 μg/kg) or subcutaneously (SC; range 5.0–800 μg/kg) in a weekly or biweekly dosing schedule. The primary objectives of the study were to identify the RP2D (part 1) and to characterize the safety and tolerability of talquetamab at the RP2D (part 2). Adverse events (AEs) were graded by Common Terminology Criteria for Adverse Events (CTCAE) v4.03, and cytokine release syndrome (CRS) was graded per Lee 2014 criteria. Response was assessed per International Myeloma Working Group criteria. All patients provided informed consent.

Results

As of Feb 8, 2021, 174 patients received talquetamab IV (n=102) or SC (n=72). Across parts 1 and 2 of the study, 28 patients were treated at the RP2D, identified as weekly SC 405 μg/kg, with 10.0 and 60.0 μg/kg step-up doses. Patients treated at the RP2D had a median age of 61.5 years (range 46–80 years) and had received a median of 5.5 prior lines of therapy (range 2–14; 100%/79% triple-class/penta-drug exposed; 71%/18% triple-class/penta-drug refractory; 86% refractory to last line of therapy; 21% with prior B-cell maturation antigen–directed therapy). No dose-limiting toxicities occurred at the RP2D in part 1 of the study. The most common AEs at the RP2D were CRS (79%; 4% were grade 3; median time to onset was day after SC dose), neutropenia (64%; 54% were grade 3/4), anemia (57%; 29% were grade 3/4) and dysgeusia (57%; all were grade 1/2). Infections were reported in 32% of patients (4% were grade 3/4) and neurotoxicity reported in 7% (no grade 3/4 events). In all, 75% of patients who received the RP2D had skin-related AEs, none of which were grade 3/4, including 18% with nail disorders. In response-evaluable patients (n=24), the overall response rate at the RP2D was 63%, with 50% reaching very good partial response or better; 9/17 (53%) evaluable triple-class refractory patients and 3/3 (100%) penta-drug refractory patients had a response. The median time to first confirmed response at the RP2D was 1.0 month (range 0.2–3.8). Responses were durable and deepened over time; the median follow-up was 6.2 month [range 2.7–9.7+] for responders at the RP2D. Talquetamab exposure at the RP2D was maintained over the maximum EC target level from an ex vivo cytotoxicity assay. Consistent T cell activation was also observed at the RP2D.

Conclusion

Talquetamab, at the RP2D of weekly 405 μg/kg SC, demonstrated a high clinical response rate and was well-tolerated in patients with relapsed/refractory MM. Based on the pharmacokinetic data, other SC dosing strategies are also being explored. The promising efficacy and safety profile, and the convenience of SC dosing support monotherapy development and combination approaches with this novel agent.

Keyword(s): Immunotherapy, Malignancy, Multiple myeloma

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