At the 2023 American Society of Clinical Oncology (ASCO) annual meeting in Chicago, Illinois, Carolina Schinke, MD, University of Arkansas, Little Rock, Arkansas, discussed updated findings from the MonumenTAL-1 trial which indicated that patients with heavily pretreated R/R multiple myeloma had impressive responses to talquetamab, a GPRC5D-CD3 bispecific antibody. 

Transcript: 

Hi, my name is Carolina Schinke. I am an associate professor at the University of Arkansas for Medical Science, where I work at the Myeloma Center. Today, I want to present the results, or the update of, MonumenTAL-1, which is a phase 1/2, clinical study of single-agent talquetamab, a GPRC5D, a specific antibody in heavily pre-treated multiple myeloma patients. 

The monumental 1/2 trial included 3 cohorts. Cohorts A and B both included approximately 140 patients and were single-agent talquetamab in patients [who] were naive to T-cell redirecting treatment. Cohort A used a dosing schedule of talquetamab weekly. Cohort B [used] a dosing schedule of talquetamab every other week. Cohort C included 51 patients who had previously received T-cell directing treatment or BCMA-targeting treatment. 2/3 of these patients in cohort C had been exposed to BCMA CAR T-cell treatment, and approximately 1/3 had BCMA-targeting bispecifics.

In terms of patient characteristics across the board, these were patients heavily pretreated with multiple lines of treatment, approximately 5 to 6 lines. Most of them, the majority were triple-refractory, [and] approximately 20% to 30% were penta-refractory. Median age was similar, around 60 to 65 for cohort A and cohort B. I believe cohort C patients were a tad younger, at 61 years.

In terms of overall response, we saw impressive results. Cohort A and cohort B had overall response rates of over 70%. Cohort C, [which] again, is the patient group that had prior T-cell redirecting treatment, [had an] overall response rate [of] 65%. We saw a little bit of difference in patients who had previous CAR T-cell treatment. The other response rate was a little bit better– 85% compared to those who had prior BCMA targeting bispecific therapy where [the] overall response rate was 44%. Again, this is still early data, and also maybe small patient numbers. We'll have to see how that also changes with time. Maybe also with the larger patient numbers to be treated on this trial or in future trials.

In terms of the duration of response, we also saw very impressive results. Interesting results. [In] cohort A, where we had the weekly dosing schedule, [the] duration of response was 9.5 months, which was a little bit longer in cohort B, where it was around 11 to 12 months. Again, interesting why that would be. Maybe it has to do with the exhaustion of T-cells. We think that having a larger treatment break between those administered doses is beneficial and will maybe lead to [an] improved duration of response over time. So, that's also something to see. [In] cohort C, which had dosing schedules that were mixed weekly and every other week, dosing had an overall duration of response of approximately 9.5 months. 

Median progression-free survival was 35 months for cohort A and 54 months for cohort B. We see there [is] a little bit of a difference with longer median progression-free times for cohort B, which had this every-other-week dosing schedule. Again, [this] may be in line with if we are able to optimize the dosing schedule. Maybe that also can improve [the] efficacy of bispecific antibody treatment. [In] cohort C for patients with prior T-cell redirecting treatment, [the] median progression-free survival was 38 months. That was a mix of weekly and biweekly, or every other week, scheduled doses.

Side effects or adverse events across the board for all cohorts were mainly skin, nail, and oral changes, dysgeusia. These were relatively mild grade 1 and grade 2, and especially skin and nail changes were mostly cosmetic and could also be treated with aggressive hydration creams. Supportive measures could improve these alterations to some degree.

None of the patients had to come off the trial for these adverse events. In terms of infections, we saw relatively low rates, particularly for grade 3 and 4 infections. These were less than 20% in cohort A and cohort B, a little bit higher in those that previously had received T-cell directing treatment. In cohort C, we had less than 30% grade 3/4 infections. Overall, it was deemed that talquetamab is a very safe [and] effective drug in this heavily pretreated patient population.

The conclusions are that talquetamab as a single-agent treatment in heavily pretreated patients with at least 4 prior lines had impressive responses to single-agent talquetamab and with a very manageable side effect profile. Thank you.

Source: 

Schinke, C, Touzeau C, Minnema MC, et al. Pivotal phase 2 MonumenTAL-1 results of talquetamab (tal), a GPRC5DxCD3 bispecific antibody (BsAb), for relapsed/refractory multiple myeloma (RRMM). Presented at the ASCO Annual Meeting; June 2-6, 2023; Chicago, Illinois. Abstract 8036.