Mutant IDH1 inhibitor ivosidenib (IVO; AG-120) in combination with azacitidine (AZA) for newly diagnosed acute myeloid leukemia (ND AML).
Bibliographic record
Abstract
7011 Background: IVO, a mutant IDH1 (mIDH1) inhibitor, is approved for the treatment of relapsed/refractory mIDH1 AML. We report results from an ongoing phase 1b study of patients (pts) with mIDH1 ND AML ineligible for intensive treatment who received combination IVO+AZA (NCT02677922). Methods: Pts received oral IVO 500 mg daily continuously and subcutaneous AZA 75 mg/m 2 on D1–7 in 28-d cycles. ORR comprised CR + CRi/CRp + PR+ MLFS. CR with partial hematologic recovery (CRh) was defined as CR with ANC > 0.5×10 9 /L and platelets > 50×10 9 /L. Exploratory analysis included digital PCR assessment of m IDH1 allele frequency in bone marrow mononuclear cells (≤0.04% sensitivity). Results: As of 9Oct2018, 23 pts received IVO+AZA (11 male; median age 76 yrs [range 61–88]). Median duration of exposure was 11 mo (0.3–25.3); 12 pts remained on treatment at data cutoff. All-grade adverse events (AEs) regardless of cause in ≥30% pts were thrombocytopenia (65%), nausea (61%), diarrhea (57%), anemia (52%), constipation (52%), febrile neutropenia (39%), pyrexia (39%), vomiting (35%), fatigue (35%), hypokalemia (35%), dizziness (35%), insomnia (35%), and neutropenia (30%). AEs of special interest included ECG QT prolonged (26%), IDH differentiation syndrome (17%), and leukocytosis (13%). Grade 3/4 AEs in ≥10% pts were thrombocytopenia (61%), anemia (44%), febrile neutropenia (39%), neutropenia (26%), sepsis (22%), and ECG QT prolonged (13%). ORR was 78% (n = 18): CR 57%, CRi/CRp 13%, and MLFS 9%. CR+CRh rate was 70% (n = 16). Median time to response was 1.8 mo (0.7–3.8) and to CR 3.5 mo (0.8–6.0); median response duration not yet reached. m IDH1 clearance was seen in 10/16 pts (63%) with CR/CRh, including 9/13 (69%) with CR. Conclusions: IVO+AZA was well tolerated with a safety profile consistent with IVO or AZA monotherapy. All-grade cytopenia-related AEs were infrequent relative to other non-intensive therapies. CR and ORR rates exceeded those of AZA alone (Dombret et al., Blood 2015) and most responders achieved m IDH1 mutation clearance. Based on these findings, a phase 3 double-blind placebo-controlled study of IVO +AZA (AGILE, NCT03173248) is actively enrolling pts. Clinical trial information: NCT02677922.
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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 | 0.006 | 0.005 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.003 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.003 |
| 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".