P-030: First Results From the RedirecTT-1 Study With Teclistamab (tec) + Talquetamab (tal) Simultaneously Targeting BCMA and GPRC5D in Patients (pts) With Relapsed/Refractory Multiple Myeloma (RRMM)

Introduction: Tec is the only approved BCMA×CD3 bispecific antibody with a personalized, weight-based, and flexible dosing schedule for the treatment of triple-class exposed RRMM. Tal, a bispecific antibody targeting the novel myeloma antigen GPRC5D, has shown promising efficacy in pts with RRMM. By simultaneously targeting 2 validated myeloma target antigens, using tec + tal in combination may lead to improved outcomes by overcoming resistance mechanisms, such as antigen escape. Here, we report the first results from the phase 1b RedirecTT-1 trial (NCT04586426) in pts with RRMM.

Methods: Enrolled pts had MM per International Myeloma Working Group 2016 criteria; were relapsed/refractory or intolerant to the last line of therapy (LOT); were exposed to a proteasome inhibitor, immunomodulatory drug, and anti-CD38 therapy; and had measurable disease. The primary objectives are to evaluate safety and identify a recommended phase 2 regimen (RP2R) for the combination. Responses were investigator-assessed. 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 Dec 12, 2022, 63 pts had received tec + tal. Median (range) age was 67 years (39–81); median (range) prior LOT was 5 (1–11); 33% (15/45) had high-risk cytogenetics; 78% (49/63) were triple-class refractory; 63% (40/63) were penta-drug exposed; and 43% (27/63) had extramedullary disease (EMD; all bone independent). Median (range) duration of follow-up was 14.4 months (0.5–21.9). The most common treatment-emergent AEs were CRS (81%; grade [gr] 3, 3%, no gr 4), neutropenia (76%; gr 3/4, 75%), and anemia (60%; gr 3/4, 43%). Dose-limiting toxicities (DLTs) were reported at dose level 1 (gr 3 herpetic stomatitis) and dose level 3 (gr 3 AST/ALT elevation). 1 ICANS event was reported at dose level 3. No DLTs were reported at the RP2R. Across all dose levels, overall response rate (ORR) was 84% (52/62) among all evaluable pts and 73% (19/26) among evaluable pts with EMD; rate of complete response or better (≥CR) was 34% (21/62) and 31% (8/26), respectively. At the RP2R, ORR was 92% (12/13) among all evaluable pts and 83% (5/6) among evaluable pts with EMD; rate of ≥CR was 31% (4/13) and 33% (2/6), respectively. Median duration of response has not been reached. Updated data, with 19 additional pts at the RP2R, will be presented.

Conclusions: In this first combination study of two bispecific antibodies in MM, targeting BCMA and GPRC5D, tec + tal at the RP2R has a manageable safety profile consistent with each of the monotherapies. A 92% ORR was observed in pts with advanced RRMM at the RP2R and an ORR of 83% was achieved in pts with EMD, a high-risk population with unmet need, supporting further evaluation of the combination. © 2023 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2023 ASCO Annual Meeting. All rights reserved.