RedirecTT-1 Study: Dual Targeting of Relapsed Myeloma with Teclistamab and Talquetamab

Exploring the results of the RedirecTT-1 study

Dr. Yael Cohen, presents the results of the RedirectT-1 study, which combines the use of two bispecific antibodies, Teclistamab (TEC) and Talquetamab (TAL), for the treatment of relapsed refractory multiple myeloma (RRMM). The study aimed to evaluate the safety and anti-cancer activity of the regimen in patients who were intolerant or refractory to established therapies. The results showed manageable safety profiles, with manageable hematological and non-hematological adverse events. The overall response rate was 86.6%, and the median duration of response was not reached. The combination therapy demonstrated promising results, especially in patients with extramedullary disease.

• The RedirecTT-1 study combines Teclistamab (TEC) and Talquetamab (TAL)  antibodies for the treatment of relapsed refractory multiple myeloma (RRMM).
• Teclistamab is the first and only approved BCMA bispecific antibody for treating myeloma, with response rates over 60% in heavily pre-treated patients.
• Talquetamab is an advanced GPRC5D-directed bispecific antibody, with response rates above 70%.
• The trial enrolled 93 patients, including 34 in the recommended phase two dose.
• Patient characteristics included a high rate of extramedullary plasmacytoma, four prior lines of therapy, and triple refractory status.
• Hematotoxicity, primarily neutropenia, occurred in over 60% of patients, with a low rate of febrile neutropenia.
• Grade three to four non-hematological events were relatively low and manageable.
• Skin, mouth, and nail toxicities associated with Talquetamab were mostly low-grade.
• Cytokine release syndrome occurred in 76% of patients, primarily grade one.
• The overall response rate was 86.6%, with a response rate of 96.3% in the recommended phase two dose group.
• Median duration of response was not reached, indicating durable responses.
• Patients with extramedullary disease had an overall response rate of 71.4% across all dose levels and 85.7% in the recommended phase two regimen.
• An example patient showed a significant reduction in mass size and deep response after treatment.
• The combination therapy demonstrated competitive results with CAR-T cell therapies, particularly in patients with extramedullary soft tissue plasmacytomas.

Authors:
Yael C Cohen, Daniel Morillo, Moshe E Gatt, Michael Sebag, Kihyun Kim, Chang-Ki Min, Albert Oriol, Enrique M Ocio, Sung-Soo Yoon, Maria-Victoria Mateos, Michael Chu, Paula Rodríguez-Otero, Irit Avivi, Yue Guo, Maria Krevvata, Michelle R. Peterson, Melissa Jo Beelen, Jill Vanak, Arnob Banerjee, Hila Magen

Clinical trial information: NCT04586426