Dr Popat on the Rationale for Assessing JNJ-5322 in Relapsed/Refractory Myeloma

“This is a novel antibody. It's been augmented such that the BCMA/GPRC5D binding is very tight. Of note, it binds to different epitopes than teclistamab and talquetemab.”

Rakesh Popat, MBBS, MRCP, FRCPath, PhD, a consultant hematologist at the University College Hospital at the University College London Hospitals (UCLH), lead of the Myeloma Clinical Trials Program, and the cancer program lead for the National Institute for Health Research UCLH Clinical Research Facility, detailed the impetus for evaluating the novel trispecific antibody JNJ-79635322 (JNJ-5322), and the mechanism of action of the agent, for the treatment of patients with relapsed/refractory multiple myeloma.

Several bispecific antibodies have been approved by the FDA for the treatment of patients with multiple myeloma, which include teclistimab-cqyv (Tecvayli) and elrantamab (Elrexfio), which target BCMA, Popat began. Talquetamab-tgvs (Talvey) is also an FDA-approved treatment that targets GPRC5D, he added. However, in patients with relapsed/refractory multiple myeloma, approximately 40% do no respond to these 3 respective treatments, he emphasized. Although talquetamab is an effective bispecific antibody, it’s known to be associated with on-target, off-tumor toxicities, which include skin, nail, and oral toxicities, such as dry mouth and problems with taste, he asserted. Therefore, the purpose of the phase 1 trial (NCT05652335) was to develop a trispecific antibody that could target BCMA-positive cells, along with GPRC5D-positive cells, according to Popat. With the specificity of the molecule, the hope is to reduce off-tumor toxicities, he stated.

Regarding the mechanism of action of JNJ-5322, it’s a novel trispecific antibody, of which the BCMA and GPRC5D binding is very tight, Popat noted. It can bind to different epitopes compared with teclistamab and talquetamab, he continued. Furthermore, the CD3 portion of the agent is a low-affinity binder that can better lend itself for outpatient dosing, which also leads to a lower cytokine release syndrome profile, he contextualized. Additionally, the modulation of this component further improved pharmacokinetics, which allows for dosing every 2 to 4 weeks, he concluded.