Final safety and efficacy results from a phase 1/2 study of tagraxofusp, a CD123-targeted therapy, for myelofibrosis
Bibliographic record
Abstract
Patients with myelofibrosis (MF) who are resistant to or relapse after Janus kinase inhibitor (JAKi) therapy have limited treatment options and typically poor prognoses. CD123 is overexpressed in various myeloid malignancies, including MF. Tagraxofusp is a first-in-class CD123-targeted therapy, and the only drug approved globally for the rare myeloid malignancy blastic plasmacytoid dendritic cell neoplasm. We conducted a phase 1/2 trial to determine optimal dosing, and evaluate safety and efficacy of tagraxofusp monotherapy in treatment-naïve (n = 5) MF and patients with MF resistant/refractory to JAKi (n = 25) and not eligible for stem cell transplant. There were no dose-limiting toxicities. The recommended phase 2 dose of tagraxofusp was 12 μg/kg per day for 3 consecutive days per cycle. In the safety population (n = 36) treated at 12 μg/kg per day, the most frequent grade ≥3 treatment-emergent adverse events were thrombocytopenia (19%), anemia (22%), and dyspnea (11%). Capillary leak syndrome occurred in 11% of patients, all during cycle 1 with resolution in all patients. Thirty patients treated at 12 μg/kg per day were efficacy evaluable. Of 18 (n = 2 treatment-naïve, n = 16 relapsed/refractory) patients with baseline splenomegaly, 2 relapsed/refractory patients had spleen volume reduction ≥35%. In relapsed/refractory patients, 40% had total symptom score (TSS) ≥50%, and median overall survival (OS) was 19.3 months. In patients who were treatment naïve, 40% had TSS ≥50%, and median OS was 26.6 months. In this trial, tagraxofusp monotherapy in MF was well tolerated, without cumulative myelotoxicity, and with symptom score improvements, warranting further investigation in combination therapy. This trial was registered at www.clincaltrials.gov as #NCT02268253.
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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 | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 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".