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Updated Phase I Results Show Response in R/R MM With Talquetamab, Recommended Phase II Doses

June 7, 2022

Mid-July 2022

Tess Stafford

Tess Stafford is the editorial assistant of ASH Clinical News.

The first-in-class bispecific antibody talquetamab has an anticipated safety profile and demonstrated efficacy for the treatment of relapsed/refractory (R/R) multiple myeloma (MM) in heavily pretreated patients, according to updated results from the phase I MonumenTAL-1 trial. Monique C. Minnema, MD, PhD, of University Medical Center Utrecht in the Netherlands, presented the study results at the European Hematology Association (EHA) 2022 Congress. The study was also presented at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting.

Talquetamab is a G protein-coupled receptor family C group 5 member D (GPRC5D) x CD3 bispecific antibody. The antibody targets the antigen GPRC5D, which is highly expressed in malignant plasma cells, and induces T-cell-activated lysis. 

The MonumenTAL-1 trial was open to patients with R/R MM as well as those who could not tolerate standard treatment. Researchers sought to determine the safety and efficacy of talquetamab and to identify recommended phase II doses. Researchers found two recommended phase II doses and split patients into two treatment groups:

  • 405 μg/kg subcutaneous (QW; n=30)
  • 800 μg/kg subcutaneous every other week (Q2W; n=44)

Step-up dosing was used to avoid adverse events (AEs) like severe cytokine release syndrome (CRS).

As of April 6, 2022,* 100% of patients in the 405 μg/kg QW group were triple-class (TC) exposed and 77% were TC refractory, similar to 98% and 77%, respectively, of patients in the 800 μg/kg Q2W group. Patients in the 405 μg/kg QW group received a median of six prior lines of therapy, and patients in the 800 μg/kg Q2W group received a median of five.

Researchers found cytopenias and CRS to be the most frequently occurring AEs. Cytopenias were confined to step-up and cycle 1-2 doses primarily and were found to be reversible within about one week. CRS (77% vs. 80% in the 405 μg/kg QW group vs. 800 μg/kg Q2W group, respectively; grade 3: 3% vs. 0%), was mostly grade 1 or 2 and confined to the step-up doses and first full dose.

Other side effects of talquetamab found in the 405 μg/kg QW group and 800 μg/kg Q2W group during the trial included infections (47% vs. 39%; grade 3/4: 7% vs. 9%), skin- (67% vs. 73%) and nail-related disorders (60% vs. 34%), and dysgeusia (63% vs. 57%).

“We learned from each other how to manage [dysgeusia] using dose reductions and delays while keeping our patients in their remission status,” Dr. Minnema said.

There were no deaths from drug-related AEs.

The overall response rate in the 405 μg/kg QW group was 70%, and 64% in the 800 μg/kg Q2W group. Very good partial responses were seen in 57% of patients in both groups. The median time to first confirmed response among patients in the 405 μg/kg QW group was 0.9 months (range = 0.2-3.8) and 1.2 months (range = 0.3-6.8) in the 800 μg/kg Q2W group. The median patient follow-up was 13.2 months (range = 1.1-24.0) in the 405 μg/kg QW group compared to 7.7 months (range = 0.7-16.0) in the 800 μg/kg Q2W group.

According to Dr. Minnema, although there is more research to be done on the use of talquetamab in combined R/R MM immunotherapy, she is optimistic it will change practice and give hope to many patients.

“We are already performing combination studies of talquetamab with other drugs to start elucidating some of these aspects in the near future,” Dr. Minnema said.

Any conflicts of interest by the authors were made public at the time of presentation.

*This article includes updated data that were provided by the author after the study was presented at the EHA 2022 Congress.

Reference

Minnema MC, Krishnan A, Berdeja JG, et al. Talquetamab, a G protein-coupled receptor family C group 5 member D D x CD3 bispecific antibody, in relapsed/refractory multiple myeloma: updated efficacy and safety results from MonumenTAL-1. Abstract S182. Presented at the European Hematology Association (EHA) 2022 Congress, June 11, 2022; Vienna, Austria.

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