Combination treatment with teclistamab and talquetamab has demonstrated activity in patients with relapsed or refractory multiple myeloma (MM), according to research presented at the EHA 2023 Hybrid Congress.

Teclistamab and talquetamab produced a 96% response rate when given at the recommended phase 2 dose, making the combination competitive with chimeric antigen receptor (CAR) T-cell therapies, according to study presenter Maria-Victoria Mateos, MD, PhD, of the University of Salamanca in Spain.

Dr Mateos noted that this is the first-ever reported dual bispecific combination in hematologic malignancies. Talquetamab targets GPRC5D and CD3, and teclistamab targets BCMA and CD3.

Researchers are evaluating teclistamab and talquetamab in the ongoing phase 1/2 RedirecTT-1 trial (ClinicalTrials.gov Identifier: NCT04586426), and Dr Mateos reported results from 93 patients enrolled in this trial. 

The patients had relapsed or refractory MM, and all had prior exposure to a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 monoclonal antibody. At baseline, the median age was 65 (range, 39-81) years, 51.6% of patients were men, and the median number of prior lines of therapy was 4 (range, 1-11). 


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Thirty-four patients received the recommended phase 2 dose of the study drugs, which was teclistamab at 3 mg/kg and talquetamab at 0.8 mg/kg, both given every other week.

The median follow-up was 13.4 months overall and 8.1 months in patients who received the recommended phase 2 dose. At the data cutoff, 57 patients (61%) were still on study treatment.

The overall response rate was 86.6% in the entire cohort and 96.3% in patients who received the recommended phase 2 dose. The complete response rates were 40.2% and 40.7%, respectively. The median duration of response was not reached in either group. 

The median progression-free survival was 20.9 months in the overall cohort and was not reached in patients who received the recommended phase 2 dose. The 9-month progression-free survival rate was 70.1% and 77.1%, respectively.

Treatment-emergent adverse events (TEAEs) were reported in 96.8% of patients overall and 94.1% of patients receiving the recommended phase 2 dose. The rate of grade 3-4 TEAEs was 88.2% and 79.4%, respectively.

The incidence of cytokine release syndrome (CRS) was 76.3% overall and 73.5% among patients receiving the recommended phase 2 dose. The median time to CRS onset was 2 days in both groups, and the median duration was 2 days in both groups. All CRS events resolved. 

There were 5 immune effector cell-associated neurotoxicity syndrome (ICANS) events in 3 patients. One was grade 3 ICANS. All other ICANS events were grade 1. 

Six patients died because of a treatment-related event, 1 of whom received the recommended phase 2 dose.

“These results support the initiation of larger studies with the combination of teclistamab and talquetamab,” Dr Mateos said.

Disclosures: This research was supported by Janssen. Dr Mateos disclosed relationships with Janssen, Celgene, Takeda, Amgen, GSK, AbbVie, Pfizer, Regeneron, Roche, Sanofi, Oncopeptides, and Streamline Pharma. No other disclosures were provided.

Reference

Mateos MV, Morillo D, Gatt M, et al. First results from the RedirecTT-1 study with teclistamab (tec) + talquetamab (tal) simultaneously targeting BCMA and GPRC5D in patients (pts) with relapsed/refractory multiple myeloma (RRMM). EHA 2023. June 8-11, 2023. Abstract S190.

This article originally appeared on Cancer Therapy Advisor