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Teclistamab is the first B-cell maturation antigen (BCMA)-directed bispecific antibody approved for the treatment of triple-class exposed, relapsed/refractory multiple myeloma (R/R MM). Talquetamab is an investigational bispecific T-cell engager antibody targeting both GPRC5D and CD3 for the treatment of patients with R/R MM. The Multiple Myeloma Hub has previously reported on talquetamab for R/R MM from the MonumenTAL trials.
Simultaneous targeting of two validated MM target antigens, with combination teclistamab and talquetamab treatment, may improve outcomes and overcome resistance mechanisms, such as antigen escape.
Cohen presented the first results from the RedirecTT-1 study (NCT04586426) of teclistamab in combination with talquetamab, simultaneously targeting BCMA and GPRC5D, in patients with R/R MM at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting.1 These are the first results of two bispecifics used in combination for a hematological malignancy. We are pleased to summarize the key findings below.
Figure 1. RedirecTT-1 study design*
Q2W, dosing every 2 weeks; RP2R; recommended phase 2 regimen; SC, subcutaneous.
*Adapted from Cohen.1
Overall, the safety profile of teclistamab with talquetamab was considered clinically manageable, with low rates of discontinuation and death (Table 1). Any grade and Grade 3/4 infections occurred in 83.9% and 52.7% of patients, respectively, and all deaths and discontinuations were due to infections.
Table 1. RedirecTT-1 safety results*
RP2R; recommended phase 2 regimen; TEAE, treatment emergent adverse event; TRAE, treatment related adverse event. |
||
TEAE, % |
All dose levels |
RP2R Dose† |
---|---|---|
Any TEAE |
96.8 |
94.1 |
Grade 3/4 TEAE |
88.2 |
79.4 |
Discontinuation due to drug-related TEAE |
6.5 |
5.9 |
Death due to drug-related TEAE |
6.5 |
2.9 |
Table 2. RedirecTT-1 hematologic safety profile
RP2R; recommended phase 2 regimen; TEAE, treatment-emergent adverse event. *Adapted from Cohen.1 |
||||
TEAE, % |
All dose levels |
RP2R Dose† |
||
---|---|---|---|---|
Any Grade |
Grade 3/4 |
Any Grade |
Grade 3/4 |
|
Neutropenia |
65.6 |
61.3 |
55.9 |
44.1 |
Anemia |
50.5 |
34.4 |
32.4 |
23.5 |
Thrombocytopenia |
43.0 |
29.0 |
32.4 |
23.5 |
Figure 2. Best response at all dose levels and RP2R at median follow-up of 13.4 months and 8.1 months, respectively*
CR, complete response; ORR, overall response rate; PR, partial response; R2PR, recommended phase 2 regimen; sCR stringent complete response; VGPR, very good partial response.
*Adapted from Cohen.1
In this first combination study of a BCMA- and GPRC5D-targeted bispecific antibody, teclistamab plus talquetamab at the RP2R dose demonstrated a clinically manageable safety profile; this was consistent with the respective monotherapy profiles, with low rates of discontinuation and death. These first results from RedirecTT-1 reported an ORR of >96% in patients receiving the RP2R dose and an ORR of >85% in patients with extramedullary disease (a high-risk population with unmet need), supporting further evaluation of the combination.
References
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