A novel, immunotherapy-based approach for the treatment of relapsed/refractory multiple myeloma (RRMM): Updated phase 1b results for daratumumab in combination with teclistamab (a BCMA x CD3 bispecific antibody).
Bibliographic record
Abstract
8032 Background: Teclistamab (tec; JNJ-64007957) is a BCMA × CD3 T-cell redirecting bispecific antibody under investigation in patients (pts) with RRMM. Daratumumab (dara) is a CD38 mAb with direct on-tumor and immunomodulatory actions. Initial clinical data from the phase 1b multicohort TRIMM-2 study support the combination of tec + dara for the treatment of RRMM, with tolerable safety, no overlapping toxicities, and promising efficacy. We present updated results with additional pts and longer follow-up. Methods: Eligible MM pts aged ≥18 y had received ≥3 prior lines of therapy (LOT; including a proteosome inhibitor [PI] and immunomodulatory drug [IMiD]) or were double-refractory to a PI and IMiD. Pts treated with anti-CD38 therapy ≤90 d prior were excluded. Pts received dara SC 1800 mg per approved schedule and tec SC 1.5–3 mg/kg QW or Q2W. Primary objectives were to identify the recommended phase 2 dose of tec for combination therapy and evaluate safety of the combination. Responses were assessed by IMWG criteria. AEs were graded per CTCAE v5.0; cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS) were graded per ASTCT guidelines. Results: At data cutoff (Jan 13, 2022; safety population: N=46), median follow-up was 7.2 mo (range 0.1–16.6; median age 67 y [range 50–79]; 52% female). Pts received a median of 6 prior LOT (range 2–17; 74% triple-class exposed; 63% penta-drug exposed; 15% anti-BCMA exposed). 91% of pts had ≥1 AE (grade 3/4 78%), most commonly CRS (61%; all grade 1/2; median time to onset 2 d; median duration 2 d), neutropenia (54%; grade 3/4 50%), anemia (46%; grade 3/4 28%), thrombocytopenia (33%; grade 3/4 28%), and diarrhea (33%; grade 3/4 2%). Infections occurred in 29 pts (63%; grade 3/4 28%). One pt had grade 1 ICANS that fully resolved. Among 37 response-evaluable pts, ORR was 78% (29/37); 27 pts (73%) had very good partial response (VGPR) or better (Table). Median time to first response across dosing cohorts was 1.0 mo (range 0.9–2.8); median duration of response was not reached. Upregulation of CD38 + /CD8 + T cells and proinflammatory cytokines was observed with tec + dara, supporting potential synergy of the combination in pts with prior anti-CD38 exposure. Updated results will be presented. Conclusions: Tec + dara provides a novel immunotherapy approach for the treatment of RRMM that may yield improved clinical efficacy in heavily pretreated pts. Clinical trial information: NCT04108195. [Table: see text]
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.006 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| 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".