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ASH 2020 | First-in-human study of talquetamab: a GPRC5D-CD3 bispecific antibody for R/R MM

Amrita Krishnan, MD, City of Hope Medical Center, Duarte, CA, discusses the results of an ongoing Phase I study (NCT03399799) of talquetamab for relapsed/refractory multiple myeloma (MM). Since expression of GPRC5D is high in primary MM cells and limited elsewhere, targeting it with talquetamab, a GPRC5D-CD3 bispecific antibody, can induce T-cell mediated cytotoxicity of MM cells. Subcutaneous (SC) and intravenous (IV) administration is being investigated in the process of establishing a recommended Phase II dose. Treatment at higher doses is ongoing, and a recommended Phase II dose will be presented. This interview took place during the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition, 2020.

Transcript (edited for clarity)

Talquetamab is a bispecific dual body T-cell engager targeting GPRC5D, which is the G-protein receptor that has some, it is expressed primarily in plasma cells, but it’s actually also expressed in hair follicles. And this is a first-in-class dual body antibody that’s biding to GPRC and to CD3. And similar to teclistamab we’ve seen that it redirects T-cells to the GPRC expressing myeloma cells and mediate cell killing...

Talquetamab is a bispecific dual body T-cell engager targeting GPRC5D, which is the G-protein receptor that has some, it is expressed primarily in plasma cells, but it’s actually also expressed in hair follicles. And this is a first-in-class dual body antibody that’s biding to GPRC and to CD3. And similar to teclistamab we’ve seen that it redirects T-cells to the GPRC expressing myeloma cells and mediate cell killing.

The trial that my colleague Dr Chari is going to present is the Phase I dose escalation trial of this agent in patients with relapsed/refractory myeloma. We looked at both IV and sub-cu dosing, and we’ll be presenting on a total of 157 patients with the primary emphasis being on the sub-cu dosing group of patients. Again, these are very heavily treated patients in the 2% with triple class exposed and refractory and 33% with penta-drug refractory. 95% had had prior daratumumab.

Side effects, again, in keeping with this class of agents, cytokine release syndrome in about 54% of patients, the majority of it were grade one and grade two. Hematologic toxicity in about 30 to 50% of patients. Anemia, neutropenia, and thrombocytopenia. Interestingly and unique for this agent, again speaking to where it is expressed, we also saw nail disorders in 13% of patients in the Phase I portion, and up to 20% in the expansion cohort. At the highest dose of 800 micrograms, we had a response rate of 73%. The overall response rate that we’re reporting out at the RP2D dose it was 69%. And again, this is still very early follow-up on these patients. Median follow-up at the RP2D dose is only 3.7 months. So again, durability of those responses remain to be seen.

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