Updated results of a phase 1, first-in-human study of talquetamab, a G protein-coupled receptor family C group 5 member D (GPRC5D) × CD3 bispecific antibody, in relapsed/refractory multiple myeloma (MM).

Authors

null

Jesus G. Berdeja

Sarah Cannon Research Institute and Tennessee Oncology, Nashville, TN

Jesus G. Berdeja , Amrita Y. Krishnan , Albert Oriol , Niels W.C.J. van de Donk , Paula Rodríguez-Otero , Elham Askari , Maria-Victoria Mateos , Monique C. Minnema , Luciano J. Costa , Raluca Verona , Suzette Girgis , Thomas Prior , Brandi Hilder , Jeffery Scott Russell , Jenna D. Goldberg , Ajai Chari

Organizations

Sarah Cannon Research Institute and Tennessee Oncology, Nashville, TN, City of Hope Comprehensive Cancer Center, Duarte, CA, Institut Català d’Oncologia and Institut Josep Carreras. Hospital Germans Trias i Pujol, Barcelona, Spain, Amsterdam University Medical Center, VU University Medical Center, Amsterdam, Netherlands, Clínica Universidad de Navarra, Navarra, Spain, Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain, Hospital Clínico Universitario de Salamanca, Salamanca, Spain, University Medical Center Utrecht, Utrecht, Netherlands, University of Alabama at Birmingham, Birmingham, AL, Janssen R&D, Spring House, PA, Janssen R&D, Raritan, NJ, Mount Sinai School of Medicine, New York, NY

Research Funding

Pharmaceutical/Biotech Company
Janssen Research & Developent, LLC

Background: New immunotherapy targets in MM are needed as patients (pts) continue to relapse. The orphan receptor GPRC5D is expressed on malignant plasma cells in MM. Talquetamab (JNJ-64407564) is a bispecific IgG4 antibody that redirects T cell killing to MM cells by binding to the novel target, GPRC5D, and CD3. We present updated results of talquetamab at the recommended phase 2 dose (RP2D) from a phase 1 trial in relapsed/refractory MM. Methods: Eligible pts with MM who had relapsed or refractory disease or were intolerant to standard therapies received talquetamab intravenously (IV; range 0.5–180 µg/kg) or subcutaneously (SC; range 5.0–800 µg/kg) weekly or biweekly. Primary objectives were identification of the RP2D (part 1) and talquetamab safety and tolerability at the RP2D (part 2). Adverse events (AEs) were graded by CTCAE v4.03 (cytokine release syndrome [CRS] per Lee 2014). Response was assessed per IMWG criteria. Results: As of Feb 8, 2021, 174 pts received talquetamab, 102 by IV and 72 by SC; in parts 1 and 2, 28 pts were treated at the RP2D, identified as weekly SC 405 µg/kg, with 10.0 and 60.0 µg/kg step-up doses. Pts treated at the RP2D had a median age of 61.5 y (range 46–80) and 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. Most common AEs at the RP2D were CRS (79%; grade 3 4%; median time to onset: day after SC injection), neutropenia (64%; grade 3/4 54%), anemia (57%; grade 3/4 29%) and dysgeusia (57%; all grade 1/2); infections were reported in 32% of pts (grade 3/4 4%) and neurotoxicity in 7% (grade 3/4 0). In all, 75% of pts dosed at the RP2D had skin-related AEs (grade 3/4 0), including 18% with nail disorders. The overall response rate at the RP2D in response-evaluable pts (n = 24) was 63%, with 50% reaching very good partial response or better; 9/17 (53%) evaluable triple-class refractory pts and 3/3 (100%) penta-drug refractory pts had a response. Median time to first confirmed response at the RP2D was 1.0 mo (range 0.2–3.8); responses were durable and deepened over time (median follow-up 6.2 mo [range 2.7–9.7+] for responders at the RP2D). At the RP2D, exposure was maintained over the maximum EC90 target level from an ex vivo cytotoxicity assay, and consistent T cell activation was seen. Conclusions: At the RP2D of weekly 405 µg/kg SC, talquetamab showed a high clinical response rate and was well-tolerated in pts with relapsed/refractory MM; based on pharmacokinetic data, other SC dosing strategies are being explored. The promising efficacy, safety profile and convenience of SC dosing support monotherapy development and combination approaches with this novel agent. Clinical trial information: NCT03399799

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Abstract Details

Meeting

2021 ASCO Annual Meeting

Session Type

Oral Abstract Session

Session Title

Hematologic Malignancies—Plasma Cell Dyscrasia

Track

Hematologic Malignancies

Sub Track

Multiple Myeloma

Clinical Trial Registration Number

NCT03399799

Citation

J Clin Oncol 39, 2021 (suppl 15; abstr 8008)

DOI

10.1200/JCO.2021.39.15_suppl.8008

Abstract #

8008

Abstract Disclosures