Dose escalation study of the HLA-A2-WT1 CD3 bispecific antibody RO7283420 in relapsed/refractory acute myeloid leukemia
Bibliographic record
Abstract
A novel T-cell bispecific antibody (TCB) RO7283420 engaging CD3 and HLA-A2-WT1 complex was evaluated in this open-label, multicenter, dose-escalation, phase 1 study (NCT04580121) which aimed to characterize safety/tolerability, determine the maximum tolerated dose (MTD), and recommend a phase 2 dose for relapsed/refractory acute myeloid leukemia patients in two groups: hematologic (Group I, n=57) and molecular (Group II, n=5) relapse. In Group I, 51 received RO7283420 intravenously (IV) and 6 subcutaneously. IV doses ranged 0.15–4 mg (flat, n=13) and 3–18 mg (step-up, n=34) administered every 3 weeks (Q3W), or 9 mg weekly (step-up, n=4). The MTD was 1/3/12 mg Q3W. The most frequent adverse event in the overall population was cytokine release syndrome (61.3%), with grade ≥3 in 9.7%. Twelve dose-limiting toxicities were reported in 11 patients and 12 (19.4%) experienced grade 5 adverse events, including one hemophagocytic lymphohistiocytosis case related to RO7283420. Among 42 efficacy-evaluable IV patients in Group I, 4.8% achieved complete remission (CR), and 2.4% achieved CR with incomplete hematologic recovery. RO7283420 induced pharmacodynamic changes in peripheral blood (PB) at doses ≥1 mg, including significant T-cell activation and expansion in PB and bone marrow (BM). Significant associations were found between blast reduction and baseline immunophenotype, including lower regulatory T cells and higher non-exhausted CD8+ T cells in BM. While dose escalation was discontinued due to limited efficacy and lack of exposure-BM response relationship, the observed pharmacodynamics underscore the promising potential of this class of TCBs targeting intracellular antigens.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.002 |
| Insufficient payload (model declined to judge) | 0.001 | 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 source (direct Gemma or distilled Codex), 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".