Updated results from the Phase 1b RedirecTT-1 study, evaluating the combination of talquetamab (Talvey) and teclistamab (Tecvayli), demonstrate high response rates and durable responses in patients with relapsed or refractory multiple myeloma (RRMM), including those with extramedullary disease. The data, presented at the 2024 International Myeloma Society Annual Meeting, suggest a consistent safety profile compared to each agent's monotherapy.
The RedirecTT-1 study (NCT04586426) is an ongoing Phase 1b dose escalation study evaluating the combination of talquetamab and teclistamab in patients with RRMM. The primary objective is to identify the recommended Phase 2 regimens (RP2R) and schedule for the study treatment and to characterize the safety of the RP2R for the study treatment.
High Response Rates and Durability
At data cutoff, 44 patients were treated with the recommended phase 2 regimen (RP2R) of 0.8 mg/kg of talquetamab in combination with 3 mg/kg of teclistamab every other week. The overall response rate (ORR) was 79.5%, with a complete response or better (CR+) rate of 52.3%. The 18-month duration of response (DOR) was 85.9%, and the 18-month progression-free survival (PFS) rate was 69.8% with a median follow-up of 18.2 months.
"As multiple myeloma progresses, it becomes more difficult to treat, especially in patients with extramedullary disease, which spreads beyond the bone marrow and typically becomes resistant to standard therapies," said Yael Cohen, M.D., Head of Myeloma Unit, Hematology Institute, Tel Aviv Sourasky Medical Center, Israel, and principal study investigator. "These results reflected promising efficacy and a manageable safety profile for this combination of two first-in-class, innovative bispecific therapies and provides a potentially promising off-the-shelf option for patients with advanced multiple myeloma."
Efficacy in Extramedullary Disease
Subgroup analysis of patients with extramedullary disease (EMD; ≥1 bone-independent lesion of ≥2 cm), a population often facing limited treatment options, demonstrated meaningful ORR and DOR for bispecific antibody-based treatment. At the RP2R (n=18), results showed an ORR of 61.1%, with a CR+ rate of 33.3%, an 18-month DOR of 81.8%, and an 18-month PFS rate of 52.9% in patients with EMD at median follow-up of 13.6 months.
Safety Profile
The combination of talquetamab and teclistamab had a safety profile consistent with the known safety profiles of each agent as monotherapy. The cumulative incidence of Grade 3/4 infections was slightly higher than that seen with either agent as monotherapy but plateaued from six months. Non-hematologic adverse events were generally low grade, including taste (50%) and non-rash skin (56.8%) and nail (47.7%) AEs. No patients discontinued study therapy due to cytopenias.
Implications for Multiple Myeloma Treatment
These findings suggest that the combination of talquetamab and teclistamab could offer a valuable treatment option for patients with heavily pretreated multiple myeloma, including those with extramedullary disease. The manageable safety profile and promising efficacy data support further investigation of this combination in larger clinical trials.
"Talquetamab and teclistamab have already demonstrated efficacy as standalone bispecifics in the clinical and real-world settings," said Jordan Schecter, M.D., Vice President, Disease Area Leader, Multiple Myeloma, Innovative Medicine, Johnson & Johnson. "We continue to research this innovative combination, as this study demonstrates both the efficacy and manageable safety profile of this combination, particularly in hard-to-treat patients such as those with EMD, as well as the combinability of talquetamab with other effective therapies."
