Multiple Myeloma Coverage from Every Angle

First-in-Human Trial of Bispecific IgG4 Antibody for Multiple Myeloma

By: Julia Fiederlein
Posted: Tuesday, July 20, 2021

The bispecific IgG4 antibody talquetamab demonstrated a high clinical response rate and was reported to be well tolerated at the recommended phase II dose in patients with relapsed or refractory multiple myeloma, according to Jesus G. Berdeja, MD, of the Sarah Cannon Research Institute, Nashville, and colleagues. The updated results of this first-in-human, phase I trial, which were presented during the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract 8008), support monotherapy development and combination approaches.

“The orphan receptor GPRC5D is expressed on malignant plasma cells in multiple myeloma,” the investigators commented. “Talquetamab…redirects T-cell killing to multiple myeloma cells by binding to the novel target, GPRC5D, and CD3.”

The recommended phase II dose of talquetamab was identified as 405 µg/kg weekly via subcutaneous injection in part one of the trial. In part two, the investigators sought to examine the safety and tolerability of this novel agent at the recommended phase II dose. A total of 28 patients were administered the recommended phase II dose in both parts of the trial, with 10- and 60-µg/kg step-up doses.

In part one, no dose-limiting toxicities were reported at the recommended phase II dose. Cytokine-release syndrome (79%), neutropenia (64%), anemia (57%), and dysgeusia (57%) were the most frequently reported adverse events; infections and neurotoxicity were reported in 32% and 7% of patients, respectively. The majority of patients (75%) experienced skin-related adverse events.

The overall response rate was 63%. A total of 53% and 100% of evaluable triple-class and penta-drug–refractory patients, respectively, had a response. The median duration of the time to the first confirmed response was 1 month; according to the investigators, responses were durable and deepened over time. Exposure was maintained over the maximum EC90 target level (90% effective concentrations) from an ex vivo cytotoxicity assay; consistent T-cell activation was observed.

Disclosure: For full disclosures of the study authors, visit

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