S190: 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)
Bibliographic record
Abstract
Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: Tec is the first BCMA-directed bispecific antibody approved 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. 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. Aims: 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 RR 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. All pts provided informed consent. The primary objectives are to evaluate safety and to identify a recommended phase 2 regimen (RP2R) for the combination. Responses were investigator assessed. 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 received tec + tal. Median (range) age was 67 y (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 mos (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). One 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 CR 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. Summary/Conclusion: In this first combination study of a BCMA- and GPRC5D-targeted bispecific antibody, 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. Keywords: Multiple myeloma, Phase I, Bispecific, B-cell maturation antigen
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".