OA – 03: Talquetamab (tal) + Teclistamab (tec) in Patients (pts) With Relapsed/Refractory Multiple Myeloma (RRMM): Updated Phase 1B Results from RedirecTT-1 With >1 Year of Follow-Up

Introduction: Tal (anti-GPRC5D) and tec (anti-BCMA) are the first bispecific antibodies approved as monotherapies for triple-class exposed (TCE) RRMM. Tal+tec may improve outcomes by redirecting T cells to 2 validated myeloma antigens. In the phase 1b RedirecTT-1 trial (NCT04586426), all dose levels (DLs), including the recommended phase 2 regimen (RP2R; tal 0.8 mg/kg + tec 3.0 mg/kg every other week [Q2W]), demonstrated promising efficacy and a safety profile consistent with each agent alone in pts with RRMM. We report updated results from RedirecTT-1 with longer median follow-up (mFU).

Methods: Pts had TCE RRMM with measurable disease per IMWG criteria and were refractory, relapsed, or intolerant to the last line of therapy (LOT). Primary objectives were to evaluate safety and identify phase 2 expansion dosing. Confirmed response was reported in all treated pts with ≥1 postbaseline disease assessment or those ending study participation without postbaseline assessments. Adverse events (AEs) were graded per CTCAE v5.0. Cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS) were graded per ASTCT criteria.

Results: As of Mar 15, 2024, 94 pts received tal+tec (44 pts at the RP2R), with a mFU of 20.3 months (18.2 months at the RP2R). Median age was 64.5 years. Median prior LOT was 4; 86.2% were triple-class refractory and 64.9% were penta-drug exposed. In total, 41.2% (21/51) pts had high-risk cytogenetics and 34 (36.2%) had extramedullary disease (EMD; ≥1 bone-independent lesion of ≥2 cm). Dose-limiting toxicities occurred in 3 pts across all DLs (grade [gr] 3 oral herpes and gr 3 elevated alanine aminotransferase/aspartate aminotransferase; gr 4 thrombocytopenia at the RP2R). The most common AEs were CRS (78.7%; gr 3, 2.1%; no gr 4/5), neutropenia (73.4%; gr 3/4, 68.1%), taste changes (64.9%; gr 3/4, not applicable), and non-rash skin AEs (60.6%; no gr 3/4). Gr 3/4 infections occurred in 63.8% of pts. ICANS occurred in 3.2% of pts (no gr 4/5). In total, 15 (16.0%) pts discontinued either tal or tec due to AEs, of which 7 (7.4%) were drug-related (5 due to infections). In total, 14 (14.9%) pts died due to AEs (11 due to infection), of which 6 (6.4%) were drug related. At the RP2R, responses occurred in 79.5% (61.1% with EMD) of pts and in 77.7% across all DLs. The probability of patients remaining in response at 18 months was 85.9% at the RP2R (81.8% with EMD) and 76.6% across all DLs. PFS at 18 months was 69.8% at the RP2R (52.9% with EMD) and 62.2% across all DLs.


Conclusions: This is the first dual-targeting bispecific antibody combination in RRMM. Tal+tec had a safety profile that was similar with each agent as monotherapy. Reponses to tal+tec were consistent across DLs, with robust durability of response at the RP2R. Efficacy in pts with EMD closely approximates outcomes in all pts, potentially overcoming the poor prognosis in high-risk populations. These results support phase 2 investigation.