Talquetamab (GPRC5D) as a New Bi-specific Antibody Treatment Option for Relapsed Multiple Myeloma

It is hard to keep up with the multiple myeloma research that is published these days, many with novel treatment targets. One example is the drug talquetamab, also known as JNJ 64407564 (from the development pipeline of Johnson & Johnson), currently being investigated to treat myeloma. This compound is a first in class novel treatment that has shown encouraging results in early studies of heavily pretreated patients with relapsed and refractory myeloma. Talquetamab is a bi-specific antibody with two targets: 

• GPRC5D (and that is shorthand for 'G protein-coupled receptor family C group 5 member D’) is a compound expressed primarily on myeloma cells but not on other cells. This makes GPRC5D an ideal target for myeloma treatment.
• CD3, a protein expressed on the surface of T-cells. T-cells are part of the body’s immune system.

When the drug binds both the myeloma and the T-cells compounds are released that kill the malignant myeloma cells.

A Phase I study was completed last year. Remember that a Phase I study in humans is designed to treat safety and efficacy of a novel compound at various dosing levels in an effort to find the dose that is the best therapeutically for future patients, without compromising the patients’ safety. Results can be summarized as follows:

• Patients characteristics were 137 patients were dosed with the study drug, at several different dose levels. The median age was 64, and 22% had stage 3 disease. The median number of prior therapies was 6, and patients had been treated for a median period of 6.5 year. 85% of the enrolled patients were refractory to their last line of therapy, 79% were triple refractory, 73% had been exposed to 5 different prior treatment drugs, 31% were refractory to 5 different treatment drugs, 10% had previously already received selenixor and 15% had received prior BCMA-directed therapy.
• 102 patients given the drug via IV-infusion, and the balance via subcutaneous injection.
• 17 patients were dosed with the recommended dose that has been chosen for the Phase II studies. This dose supports the treatment of patients either at a weekly or bi-weekly level. 
• None of these 17 patients had disease progression at a median follow-up of 3.7 months and patients continue to be monitored. Of note is the fact that at a dosing level of about 1/7th, or greater, of the recommended Phase II dose, only 16% had disease progression at a median follow-up of 7.4 months.
• No dose limiting toxicities were reported at the recommended Phase II dosing level.
• About 1/5 of the patients experienced low levels of skin toxicities.

Indications are that, at the recommended dose level talquetamab may be used as monotherapy, or single drug. This is a compound that shows solid potential for us, multiple myeloma patients, in the future, assuming that all continues to go well with the Phase II and Phase III clinical trials. Phase II studies are expected to start soon.

Those patients who are interested to learn more about the upcoming trials may wish to click on this link for trial sites, inclusion and exclusion criteria.

To learn more about bi-specific antibodies and how they work, watch our recent Myeloma Crowd Round Table here. To compare all bi-specific antibodies that are currently in development in myeloma (and there are many), click here.