Multiple Myeloma Bispecific Antibody Talquetamab Update

Johnson and Johnson/Janssen (JNJ) is almost overwhelming us, myeloma patients, with results from a substantive number of human trials in myeloma patients.

Over the past week we have seen data from five studies of teclistamab (recently discussed here), long-term follow-up results of their CAR-T product Carvykti and now we can add early results of their novel treatment talquetamab. All of this builds on their success with both Darzalex and Darzalex Faspro.

Talquetamab is a ‘first in class’ bispecific antibody that targets the GPRC5D, a new target expressed on myeloma cells, and CD3, a protein expressed on T-cells. GPRC5D has limited expression on healthy human tissue but is highly expressed on malignant myeloma cells.

This construct brings the killing T-cell in contact with the cancerous cell. JNJ has presented Phase I data with both mono treatment with talquetamab and combination treatment with talquetamab + Darzalex Faspro. Please remember that a Phase I study evaluates safety, preliminary efficacy as well as recommended Phase II dosing (RP2D) for follow-on human studies to support the registration dossiers with regulatory agencies in the future.

Talquetamab as monotherapy

Two dosing levels were identified: 405 and 800 micrograms/kg (μg/kg body weight). Patients were stepped-up gradually to the target dose in order to mitigate severe cytokine release syndrome (CRS) and required pre-medications were administered during this step-up period.

Nearly all of the patients had been triple class exposed  prior to relapse, about 75 percent. Results from these sub-programs can be summarized as follows:

Combo treatment talquetamab + Darzalex Faspro

A total of 58 patients were treated (14 with a talquetamab dose of 405 μg/kg and 44 with a dose of 800 μg/kg). Darzalex Faspro was dosed at the approved dosing level. Results can be summarized as follows:

The loss of taste/altered sense of taste was managed with managed with supportive care and, if needed, dose adjustments.” The “supportive care” was not explained as to what that entailed, though I’d say that more than a few of us would be interested in that. Please note that the patients enrolled in these two studies can be labeled as very sick.

The company and its researchers conclude that, “Results from the study show heavily pretreated patients with multiple myeloma treated with the combination, including talquetamab at the recommended subcutaneous Phase 2 dose (RP2D) administered weekly (QW) or every two weeks (Q2W), achieved high rates of responses, including for patients refractory to anti-CD38 treatment.”

Chances are quite good that we may be looking here at another future treatment option when our disease progresses, assuming, of course, that the continuation of these studies will build upon the successful outcomes of these early results and that no unforeseen regulatory obstacles will occur. It makes sense that FDA will use its best efforts to expedite the future approval of talquetamab considering that it is a truly novel “first in class” compound. That being said, we will still be several years away before we will see this addition to myeloma treatment in clinical practice, though every added treatment option provides added hope for us.