At the 2023 American Society of Clinical Oncology annual meeting, Bhagirathbhai R. Dholaria, MD, MBBS, highlighted updated results from the TRiMM-2 prospective multi-cohort trial, which demonstrated that the combination of talquetamab and daratumumab was durable, safe, and effective for patients with heavily pre-treated multiple myeloma (MM).

Transcript:

Hey, I'm Bhagi Dholaria. I'm from Vanderbilt University Medical Center in Nashville, Tennessee. I'm here at ASCO 2023 in Chicago and we'll be presenting data from our TRiMM-2 prospective multi-cohort trial in relapsed or refractory multiple myeloma, which is using [a] combination of daratumumab, a CD38 monoclonal antibody, with talquetamab, which is a new bispecific GPRC5D-targeting monoclonal antibody. This study was enrolled at multiple centers, and we'll be presenting data with additional patient and 10-month extra follow-up compared to our [European Hematology Congress] (EHA) presentation last year in 2022.

[A] total [of] 65 patients [with] heavily pretreated myeloma, previously daratumumab-refractory in most situations. We also had a handful of patients who had prior CAR T-cell therapy as well as exposure to other bispecific antibodies for their disease. These patients received 2 different dose levels of talquetamab: .4 milligrams per kilogram or .8 milligrams per kilogram in a weekly or biweekly schedule with a standard dose of daratumumab.

The major finding of this trial [was that] this drug combination was highly effective in getting the myeloma into remission. The overall response rate was over 70% in both dosing cohorts. Measures of these responses were [very-good partial response] (VGPR) or [complete response] (CR), and the responses were quite durable and deepened over time. At 1 year, the overall survival was greater than 90% in this quite aggressive disease biology, multiple myeloma patient. Even with extra additional follow-up, we did not see any new serious safety signals with this combination.

The major side effects mainly were hematological as we would expect with these combinations. However, the incidence of serious grade 3 or 4 infection was relatively low. There were [a] few opportunistic infections and [a] handful of CMV virus reactivations, but there was only one death from infection which was assigned to be treatment-related in this study. The incidence of cytokine release syndrome and neurotoxicity was quite low and most of these events were grade 1 or grade 2, and they happen during cycle 1, during the step-up dosing in majority of the cases.

In conclusion, it appears that based on the results of the TRiMM-2 cohort of combining daratumumab with talquetamab at the different dose level in heavily pre-treated multiple myeloma patients, this combination appears to be effective, even in a patient who had previously daratumumab or rituximab refractory disease. Encouraging responses were seen in a patient who had prior exposure to CAR T-cell therapy or other bispecific monoclonal antibody therapy. 

Overall, new safety signals were found and we feel that talquetamab in biweekly dosing appears to be a reasonable drug to partner with the rest of the currently available and currently under-development myeloma agents. 

Source: 

Dholaria, BR. Talquetamab (tal) + daratumumab (dara) in patients (pts) with relapsed/refractory multiple myeloma (RRMM): Updated TRIMM-2 results. Presented at 2023 American Society of Clinical Oncology conference; June 2-6, 2023; Chicago, IL. Abstract 218475