A phase 1/2, open-label study evaluating twice-daily administration of momelotinib in myelofibrosis
Why this work is in the frame
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Bibliographic record
Abstract
Momelotinib, a small-molecule inhibitor of Janus kinase 1 and Janus kinase 2, has demonstrated efficacy in myelofibrosis patients with 300 mg, once-daily dosing. This open-label, non-randomized, phase 1/2 study evaluated the safety and therapeutic benefit of momelotinib with twice-daily dosing. A total of 61 subjects with primary myelofibrosis or post-polycythemia vera/post-essential thrombocythemia myelofibrosis with intermediate- or high-risk disease received momelotinib. A phase 1 dose escalation identified 200 mg twice daily as the optimal dose to be expanded in phase 2. The most frequent adverse events were diarrhea (45.9%), peripheral neuropathy (44.3%), thrombocytopenia (39.3%), and dizziness (36.1%), the latter primarily due to a first-dose effect. The response assessment according to the 2006 International Working Group criteria (≥8 weeks duration at any time point) demonstrated spleen response by palpation of 72% (36/50) and anemia response of 45% (18/40). Spleen response by magnetic resonance imaging obtained at 24 weeks was 45.8% (27/59) for all subjects and 54.0% (27/50) for those with palpable splenomegaly at baseline. The symptoms of myelofibrosis were improved in most subjects. Cytokine analysis showed a rapid decline in interleukin-6 with momelotinib treatment, and a slower reduction in other inflammatory cytokines. In the subgroup of subjects with the JAK2V617F mutation at baseline (n=41), momelotinib significantly reduced the allele burden by 21.1% (median) at 24 weeks. These results provide evidence of tolerability and a potential therapeutic activity of momelotinib for subjects that support further evaluation in ongoing, phase 3 randomized trials. (clinicaltrials. gov identifier:01423058).
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 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 | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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 it