GPRC5D (G Protein-Coupled Receptor Class C Group 5 Member D)

P1, N=18, Recruiting, O&D BioTech Group CO., Limited

P1, N=18, Not yet recruiting, Qi deng

Multiple subclones bearing distinct genomic alterations at GPRC5D locus co-emerged within individual cases, depicting their convergent evolutionary trajectories. Of note, anti-GPRC5D TCEs with varying epitope specificity, affinity and valency differentially targeted mutant subclones, underscoring their nonredundant functional roles in overcoming resistance.

Functionally, cmRNA-based CAR-T cells elicited superior antitumor efficacy over their linear mRNA counterparts, as demonstrated by parallel lines of evidence, including in vitro antigen-specific cytotoxicity, cytokine release, and transcriptomics patterns consistent with sustained activation and absence of exhaustion signatures, as well as in vivo models demonstrating tumor elimination and prolonged survival benefits. Collectively, these findings position cmRNA as a next-generation mRNA modality for potent and controllable CAR expression, thereby providing a robust platform to unleash the full potential of mRNA technologies in cellular immunotherapy and precision medicine.

The potent and selective antitumor activity of ramantamig, with a clonal depleting ability in vitro, ex vivo, and in vivo warrants clinical evaluation of its ability to induce durable responses in myeloma. Phase 1 clinical trials are ongoing for patients with relapsed/refractory MM (NCT05652335, NCT06768489).

As GPRC5D-targeted agents advance through clinical development, large-scale prospective trials will be essential to define their therapeutic positioning and improve patient outcomes. GPRC5D is poised to become a leading next-generation target in MM immunotherapy following B-cell maturation antigen.

Adverse events were manageable and led to few treatment discontinuations. This review reports on talquetamab safety in MonumenTAL-1, with an additional pharmacy focus on strategies related to drug dispensing and clinical management.

P1, N=18, Recruiting, Chunrui Li | Trial completion date: Mar 2024 --> Oct 2025 | Trial primary completion date: Dec 2022 --> Sep 2025

The GPRC5D positivity rate in the plasma cells of patients with NDMM is associated with 1q21 gain and immune status. High GPRC5D expression at diagnosis may predict poor response to induction therapy and an unfavorable prognosis.

P1, N=12, Recruiting, Nanjing IASO Biotechnology Co., Ltd. | Trial completion date: Mar 2025 --> Oct 2026 | Trial primary completion date: Mar 2024 --> Sep 2025

Furthermore, azacitidine treatment induced GPRC5D mRNA and protein expression in hypermethylated MM cell lines. Our findings highlight that biallelic genetic inactivation and hypermethylation-driven epigenetic silencing are key mechanisms contributing to GPRC5D loss and treatment resistance.

GPRC5D is an active and safe target that shows promising results in the treatment of relapsed and/or refractory (R/R) MM and heavily pretreated patients.