TALQUETAMAB, A G PROTEIN-COUPLED RECEPTOR FAMILY C GROUP 5 MEMBER D
(GPRC5D) X CD3 BISPECIFIC ANTIBODY, IN PATIENTS WITH RELAPSED AND/OR
REFRACTORY MULTIPLE MYELOMA (RRMM): RESULTS FROM AN ONGOING PHASE 1 STUDY
Albert Oriol1, Jesus G. Berdeja2, Ajai Chari3, Niels W.C.J. van de Donk4, Paula Rodríguez-Otero5, Elham
Askari6, Maria-Victoria Mateos7, Monique C. Minnema8, Raluca Verona9, Suzette Girgis9, Thomas Prior9,
Brandi W. Hilder9, Jeffery Russell9, Jenna D. Goldberg10 and Amrita Krishnan11
(1)Institut Català d’Oncologia, Institut Josep Carreras, Hospital Germans Trias i Pujol, Barcelona, Spain
(2)Sarah Cannon Research Institute, Nashville, TN
(3)Tisch Cancer Institute, Mount Sinai School of Medicine, New York, NY
(4)Amsterdam University Medical Center, Location VU University Medical Center, Amsterdam,
Netherlands
(5)Clinica Universidad de Navarra, Pamplona, Spain
(6)Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain
(7)Hospital Clínico Universitario de Salamanca, Salamanca, Spain
(8)University Medical Center Utrecht, Utrecht, Netherlands
(9)Janssen R&D, Spring House
(10)Janssen R&D, Raritan, NJ
(11)City of Hope, Duarte
GPRC5D is an orphan receptor that is highly expressed in primary MM cells, with generally limited
expression elsewhere. Talquetamab (JNJ-64407564), a GPRC5D x CD3 bispecific antibody, induces T
cell-mediated killing of GPRC5D-expressing MM cells. We present initial results from an ongoing phase
1 study of talquetamab (NCT03399799).
Patients have MM that is RR to established therapies. Primary objectives are to characterize the safety
of talquetamab and identify a recommended phase 2 dose (RP2D). Escalating intravenous (IV) or
subcutaneous (SC) talquetamab doses ± step-up doses were assessed. Cytokine release syndrome
(CRS) was graded per Lee et al (Blood 2014). Response was assessed by investigator according to IMWG
criteria.
As of 20 Jul 2020, 137 patients had received talquetamab; 102 by IV (0.5–180 μg/kg) and 35 by SC (5–
800 μg/kg) dosing. Median age was 64 years (33–80), median prior lines of therapy (LOT) was 6 (2–20),
85% refractory to last LOT, 73%/79% triple-class/penta-drug exposed, and 31% penta-drug refractory.
13 patients (10%) had received selinexor, and 21 (15%) had prior BCMA-directed therapy.
Most frequent AEs were anemia (50%), CRS (47%), and neutropenia (45%). Most common grade 3–4
AEs were lymphopenia (37%), anemia (27%), and neutropenia (25%). CRS was mostly grade 1–2; 5
patients had grade 3 CRS that occurred with IV dosing. Only grade 1–2 CRS was seen with SC dosing.
CRS was generally confined to the first cycle, median time to onset was 1 day for IV and 2 days for SC
dosing. Seven patients (5%) had treatment-related neurotoxicity (all resolved/resolving; median
duration of 2 days 1–9): 4 grade 1–2 and 3 grade 3 events. 6/7 had neurotoxicity in the context of
CRS, including all 3 grade 3 events. 37% had infections (8% grade 3–4). Infusion-related reactions (IV;
15%) and injection-site reactions (SC; 14%) were grade 1–2 and generally occurred in cycle 1. Two
dose-limiting toxicities were observed: grade 4 increased lipase in the setting of a pancreatic
plasmacytoma (7.5 μg/kg IV) and grade 3 maculopapular rash (135 μg/kg SC). The maximum tolerated
dose has not been defined.
The half-life of talquetamab supports weekly IV dosing. Exposure increased in an approximately dose-proportional
manner following the first IV dose (1.5–60 μg/kg). SC dosing resulted in lower Cmax with
trough levels comparable to IV dosing at a similar dose. IV and SC dosing led to comparable increases
in T cell activation and cytokines (IL-10, IL-2Rα, IL-6).