Phase II clinical and molecular trial of oral ENMD-2076 in clear cell ovarian cancer (CCOC): A study of the Princess Margaret phase II consortium.
Bibliographic record
Abstract
5522 Background: CCOC is a rare chemoresistant subtype of OC. ENMD-2076 is an oral multi-target kinase inhibitor with antiangiogenic/antiproliferative profile; selective activity against the mitotic kinase Aurora A and VEGFRs, FGFRs. Methods: This is a multi-center Phase II study of ENMD-2076 in pts with recurrent CCOC and prior platinum. Primary endpoints were ORR and 6-m PFS rate. Correlative analyses include ARID1A, PTEN expression by IHC and genome sequencing by custom capture library of 555 genes. Results: Completed study enrolled 40 pts – 37 evaluable, median age of 54 (39-78). 12 pts (31%) received prior radiation and 24 (62%), 11 (28%), 4 (10%) had 1, 2 or 3 lines of chemotherapy. Archival tissue was available for 36/37 pts. Best response was PR for 2 pts (1 unconfirmed), SD for 25 (68%) and PD for 10 (26%) pts. Median PFS was 3.7 months (m) (95%CI: 3.4-4.4). ENMD was well tolerated with main related AE: hypertension (21 pts - 8 G3), nausea (18 pts -1 G3) and diarrhea (17 pts - 4 G3). By IHC, median PFS (95%CI) in ARID1A loss (19 pts) was 4.1m (3.5-10.3) vs 3.6m (1.7-3.9) in ARID1A positive (17 pts) (p = 0.024). Whilst, by IHC, PTEN was loss in 20 pts; intact in 10 and heterogeneous in 6 pts; no difference in PFS was observed. By PI3KCA mutation status, median PFS (95%CI) in wild-type (WT) (12 pts) was 5m (3.4-19.3) vs 3.7m (167-4.4) in mutated group (20 pts) (p = 0.038). Molecular profiling showed variants in PI3KCA (27%), ARID1A (26%), TP53 (7%), BRIP1 (7%), ATM (11%), BRCA1 (5%), BRCA2 (3%), RAD50 (3%), PABL2 (1%), RAD51C (1%), FANCA (1%), CTNNB1 (3%).The patient with the longest treatment duration (22m) was PTEN WT, diploid PTEN, putative bi-allelic inactivation of ARID1A. Conclusions: The PFS at 6 months was 20% for the evaluable patients, 31% in ARID1A loss and 12% in ARID1A positive patients. Loss of ARID1A, a known negative prognostic factor, was correlated with better PFS on ENMD-2076. Additional molecular profiling of the baseline biopsy material is underway. Clinical trial information: NCT01914510.
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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 | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 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".