KEY TAKEAWAYS
- The phase Ib RedirecTT-1 trial investigated tec+tal in RRMM patients.
- The study’s primary endpoint was safety and establishing the recommended Phase II regimen (RP2R) for tec+tal. Secondary outcomes were AEs, CRS, and ICANS.
- The first combination study, tec+tal at RP2R, showed a manageable safety profile consistent with each monotherapy.
The phase Ib RedirecTT-1 trial’s primary outcome was to assess the safety and the recommended Phase II regimen (RP2R) for the combination of teclistamab (tec) + talquetamab (tal) in relapsed/refractory multiple myeloma (RRMM) patients (pts). Secondary aims included monitoring adverse events (AEs), cytokine release syndrome (CRS), and immune effector cell-associated neurotoxicity syndrome (ICANS).
As of December 2022, 63 pts were treated with tec+tal, with an average follow-up duration of 14.4 months (ranging from 0.5 to 21.9 months). The median age was 67 years, spanning from 39 to 81 years. On average, pts had undergone 5 previous lines of therapy (LOT), with a range of 1 to 11. High-risk cytogenetic features were observed in 33% (15 out of 45), while 78% (49 out of 63) were refractory to all three classes of treatment. About 63% (40 out of 63) had been exposed to five different drugs, and 43% (27 out of 63) exhibited extramedullary disease (EMD), all unrelated to bone.
The most common treatment emergent adverse events (TEAEs) were CRS (81%, with 3% being grade 3 and none grade 4), neutropenia (76%, with 75% being grade 3 or 4), and anemia (60%, with 43% being grade 3 or 4). Dose-limiting toxicities (DLTs) were noted at the first and third dose levels, involving grade 3 herpetic stomatitis and grade 3 elevations in AST/ALT, respectively. Only one case of ICANS occurred at the third dose level. No DLTs were recorded at the recommended Phase II regimen.
Across all dosages, the overall response rate was 84% (52 out of 62) and 73% (19 out of 26) among those with extramedullary disease. Rates of complete response or better were 34% (21 out of 62) and 31% (8 out of 26), respectively. When focusing on the recommended Phase II regimen, the overall response rate (ORR) was 92% (12 out of 13) and 83% (5 out of 6) among pts with extramedullary disease, with rates of complete response or better at 31% (4 out of 13) and 33% (2 out of 6). The median duration of response has yet to be reached. Updated reports, including 19 more pts at RP2R, are forthcoming.
The initial study tec+tal at RP2R showed a tolerable safety profile, in line with each monotherapy. A 92% ORR in pts with advanced RRMM at RP2R and an 83% ORR in pts exhibiting EMD substantiated the need for further investigation.
Source: https://clml-soho2023.elsevierdigitaledition.com/478/index.html
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT04586426
Cohen, Y., Morillo, D., Gatt, M., Sebag, M., Kim, K., Min, C-K., Oriol, A., Ocio, E., Yoon, S-S., Mateos, M-V., Chu, M., Rodriguez-Otero, P., Avivi, I., Guo, Y., Krevvata, M., Peterson, M., Beelen, M., Vanak, J., Banerjee, A., Magen, H. MM-164 First Results From the RedirecTT-1 Study With Teclistamab (Tec) + Talquetamab (Tal) Simultaneously Targeting BCMA and GPRC5D in Patients With Relapsed/Refractory Multiple Myeloma (RRMM).
