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 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 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 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".