Dr Parrondo on the RedirecTT-1 Trial of Teclistamab Plus Talquetamab in Multiple Myeloma

Ricardo D. Parrondo, MD, hematologist/oncologist, assistant professor, Mayo Clinic, discusses the ongoing exploration of teclistamab-cqyv (Tecvayli) and talquetamab (Talvey) in the phase 1b/2 RedirecTT-1 trial (NCT04586426) in patients with relapsed/refractory multiple myeloma.

In the open-label, non-randomized trial, patients were treated with step-up dosing of teclistamab plus talquetamab at varying doses until investigators determined the recommended phase 2 regimen (RP2R), which was found to be 3.0 mg/kg of teclistamab plus 0.8 mg/kg of talquetamab administered subcutaneously every 2 weeks. Patients in the overall population received a median of 4 prior lines of therapy (range, 1-11). The primary objective of the study was to evaluate the safety of the regimen. Secondary objectives included the preliminary antitumor activity of the study treatment at the RP2R, pharmacokinetics, and immunogenicity.

The RedirecTT-1 trial utilized a BCMAxCD3 bispecific antibody in combination with a GPRC5DxCD3 bispecific antibody, unlike the phase 1 TRIMM-2 trial (NCT04108195) study, which evaluated the anti-CD30 monoclonal antibody daratumumab (Darzalex) plus subcutaneous talquetamab in relapsed/refractory multiple myeloma, Parrondo notes.

Initial results from the study presented during the 2023 ASCO Annual Meeting showed that the bispecific antibody combination achieved a response rate of 86.6% across all dose levels, and had a manageable safety profile in patients with relapsed or refractory multiple myeloma, Parrondo reports. The ORR was 96.3% among patients receiving the RP2D (n = 27). Moreover, the RP2R of the agent was also effective in patients with extramedullary soft tissue plasmacytomas, producing an ORR Of 85.7% and median duration of response that was not reached at a median follow-up of 7.2 months (range, 0.7-14.2).

Although this regimen was very effective in high-risk patients and associated with a low rate of grade 3/4 nonhematologic adverse effects (AEs), it is associated with a high incidence of any-grade cytopenia and infections, Parrondo states. A total of 94.1% of patients at the RP2R and 96.8% of those the overall study population experienced 1 or more treatment-emergent adverse events (TEAEs). However, the incidence and severity of CRS were consistent with teclistamab and talquetamab monotherapy treatment. As the regimen continues to be developed, it is important to be mindful of these AEs and the toxicity that can result from combining these two drugs, Parrondo concludes.