Phase II study of oral ENMD-2076 administered to patients (pts) with advanced soft tissue sarcoma (STS).
Bibliographic record
Abstract
10528 Background: The use of angiogenic and Aurora kinase inhibitors has been shown to abrogate tumor growth in STS. ENMD-2076 is an oral Aurora A and angiogenic kinase inhibitor that has demonstrated single-agent activity in STS cell lines and inhibition of sarcoma growth for a patient in a phase 1 clinical trial setting. Methods: This is a single-center, open-labeled phase II study of ENMD-2076 in advanced STS pts treated with ≤1 line of prior therapy in the advanced/metastatic setting. Pts were commenced on 275mg daily dose (on a 28-day cycle. Treatment-emergent adverse events were assessed by CTCAE (4.0). Radiographic or clinical tumor measurements occurred every 2 cycles (RECIST 1.1). Results: 10 pts were enrolled from 2/2013 – 11/2013 and evaluable for efficacy. Median age is 58 yrs (41 – 72). Male: Female 1:9. Histology: Leiomyosarcoma / pleomorphic sarcoma / angiosarcoma: 7/2/1. Pts received the following prior systemic therapies: doxorubicin/gemcitabine/others: 2/3/5. At time of abstract submission, median follow-up is at 7 months (2-12). 3 pts continue on study. Median number of cycles administered per pt = 2 (1-8). 2 pts had confirmed partial response (PR) and 1 pt with confirmed stable disease (SD) of > 6 months. Clinical benefit rate (PR+SD >6 months) was 30%. Median OS has not been reached. Median PFS at 1.8 months (95% CI: 1.2 – not reached). ENMD-2076 has generally been well tolerated with primarily grade 1 and 2 adverse events (AEs). Specifically, drug-induced hypertension occurred in 6 pts (grade 1-2: 4 pts, grade 3: 2 pts). Proteinuria, all grade 1-2, occurred in 6 pts. Other drug related grade 3 or 4 AEs include (pts): elevated transaminases (1), leukopenia (1), and diarrhea (1). 1 pt developed Posterior Reversible Encephalopathy Syndrome (PRES) presenting as grade 4 loss of consciousness at Cycle 1 Day 15 required ICU admission. Full neurological recovery was attained after cessation of treatment. Conclusions: ENMD-2076 has shown activity in patients with advanced STS, with meaningful clinical benefits and a side effects profile typical of this class of agent. PRES is a rare but fully reversible side effect of ENMD-2076. Clinical trial information: NCT01719744.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.005 | 0.001 |
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".