TRIMM-2 was a prospective multicohort trial in patients with relapsed or refractory multiple myeloma testing the combination of daratumumab, which is an anti-CD38 monoclonal antibody, with a novel bispecific antibody called talquetamab which is targeting G2 myeloma-associated antigen GPRC5D. We tested two different dose levels, 0.4mg/kg weekly dosing and 0.8mg/kg biweekly dosing, in combination with daratumumab.
What was the study design?
Overall we enrolled patients who had three or more lines of prior therapy with relapsed/refractory multiple myeloma or who were double refractory to proteasome inhibitor or immunomodulatory drugs. We allowed patients who had prior anti-CD38 monoclonal antibody-based therapies; the wash-out period was greater than 90 days. This study did allow prior CAR T-cell therapy or exposure to other bispecific monoclonal antibodies.
Patients received two different dose levels of talquetamab at 0.4 or 0.8mg/kg with a standard schedule of daratumumab. Patients had an opportunity to have a less frequent dosing if they had a disease response after cycle 4 and cycle 8. The primary objective of this trial was to assess the overall safety of this combination as well as understand the efficacy of this combination.
What were the results of this study?
In this meeting we will be presenting the data on 65 patients in total with an additional ten months of follow-up. When you look at this heavily pre-treated myeloma patient population, we saw that the overall response rate in either cohort was greater than 70%. The majority of the responses were either a vgPR or CR and we also noticed that most of the responses were quite rapid and they appeared to deepen over time as the patients stayed on therapy for a long period of time.
There were very few patients who actually had to stop treatment because of the AEs. There was one patient who died from infection-related complications which was thought to be related to the study intervention. But overall we did not see any additional serious safety signal compared to the talquetamab monotherapy which has already been published.
We also noted that among the patients who had prior CAR T-cell therapy or bispecific antibody therapy we saw quite encouraging overall response rates.
How could this research impact the future treatment of multiple myeloma?
It’s too early to say at this point. Both monotherapy study is still in follow-up and we are still accumulating more additional follow-up data on these patients who were treated on this trial. The whole goal of this combination is to improve upon what was achieved with single agent talquetamab which is already a good drug with more than 70% overall response rate. So we are hoping that this study will establish a new baseline of combining the talquetamab with daratumumab and also show that talquetamab can be safely combined with other myeloma-directed therapies. Multiple trials exploring different combinations of talquetamab are currently underway.
