An open-label, phase 1b, dose-escalation study (CA180-373) of dasatinib plus nivolumab, an investigational anti-programmed cell death 1 (PD-1) antibody, in patients (pts) with previously treated chronic myeloid leukemia (CML).
Bibliographic record
Abstract
TPS7119 Background: CML has become a chronic disease for many pts treated with BCR-ABL1 tyrosine kinase inhibitors (TKIs). However, new approaches are needed to increase the prevalence of deep responses suitable for treatment discontinuation and to treat resistant/recurrent CML. Immune cell–mediated approaches (eg, stem cell transplantation, interferon-α) can be effective. PD-1 ligation provides a negative costimulatory signal governing the balance between T-cell activation and tolerance. The potent second-generation TKI dasatinib may have synergy with nivolumab, a fully human IgG4 PD-1 immune checkpoint inhibitor antibody. Nivolumab has shown encouraging clinical activity against several solid tumors. PD-1 is upregulated on CD8+ T cells in CML pts (Christiansson PLoS ONE 2013;8:e55818) and blocking the PD-1/ligand interaction prolonged survival in a murine model (Mumprecht Blood 2009;114:1528-36). The study will assess safety, tolerability, and preliminary efficacy of dasatinib + nivolumab in previously treated CML in chronic or accelerated phase (CP/AP). Methods: In this open-label, phase 1b dose-escalation study, pts must be aged ≥18 years (y) and have Philadelphia chromosome–positive CML-CP/AP, ECOG performance status ≤1, and no known dasatinib-resistant BCR-ABL1 mutations. Pts must have received ≥2 prior TKIs, be progressing, or have had resistance, intolerance, or suboptimal response to the most recent therapy. Treatment in the dose-escalation phase is dasatinib 100 mg (CP) or 140 mg (AP) once daily with nivolumab 0.3 mg/kg (dose level [DL] –1), 1 mg/kg (DL 1), or 3 mg/kg (DL 2) by intravenous injection every 2 weeks for ≤2 y, followed by ≤1 y of dasatinib only. Treatment in the expansion phase will be dasatinib (same doses) + nivolumab (dose based on safety). The primary objective is to determine safety and tolerability. Secondary endpoints are major molecular response (MMR) and molecular response (MR)4.5 rates at 6, 12, 24, and 36 months and time to and duration of MMR and MR4.5 up to 36 months. Estimated completion: August 2018. Clinical trial information: NCT02011945.
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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) | 0.003 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.001 | 0.002 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.004 |
| Insufficient payload (model declined to judge) | 0.005 | 0.002 |
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".