A randomized phase II study comparing single-agent olaparib, single-agent cediranib, and the combinations of cediranib/olaparib, olaparib/durvalumab (MEDI4736), cediranib/durvalumab (MEDI4736), and olaparib/AZD5363 (capivasertib) in women with recurrent, persistent, or metastatic endometrial cancer.
Bibliographic record
Abstract
TPS5629 Background: Identifying new approaches for the treatment of advanced endometrial cancer (EC) is a priority. A platform study design allows for a faster investigation of novel drug combinations. NRG-GY012 is an ongoing platform study investigating drug combinations with the PARP inhibitor olaparib (O) and the anti-angiogenic agent cediranib (C). Results from the first set of arms established improved PFS for combination cediranib/olaparib over C alone, but did not meet its prespecified statistical significance. In this second set of arms, based on preclinical data, we are investigating the combination of O with an AKT inhibitor (capivasertib), O with durvalumab and C with durvalumab compared to the reference arm of C alone. Methods: This is a multicenter randomized four arm study for patients with recurrent, metastatic or persistent EC. Patients are randomized 1:1:1:1 to cediranib PO 30 mg Daily; olaparib 300 mg PO BID and capivasertib 400mg 4 day on/3 off schedule; olaparib 300 mg PO BID and durvalumab 1500mg q28 days; or the combination of cediranib 20 mg PO Daily 5 days on/2 days and durvalumab 1500mg q28. All treatment cycles are 28 days. Primary endpoint is progression free survival (PFS). The study is powered to detect a doubling in median PFS from 3.6 (based on cediranib alone) to 7.2 months with 90% power, using a one-sided test with α = 0.05 per comparison. Forty patients will be enrolled per arm, with an interim futility analysis planned at 50% information time. Eligibility includes endometroid, serous, and mixed histology EC; at least 1 prior line of chemotherapy (no more than 2 lines for metastatic disease), prior endocrine or immunotherapy alone is allowed; prior treatment with lenvatinib and pembrolizumab is excluded. Archival tumor tissue and blood samples are being collected for translational studies. The study is open across the NRG network; 76 of a planned 168 patients are enrolled to date. Safety analysis at the time of 36 patients enrolled did not demonstrate any new safety signals and the study was approved to continue enrollment. Clinical trial information: NCT03660826 .
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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 | 0.004 | 0.003 |
| Meta-epidemiology (narrow) | 0.003 | 0.001 |
| Meta-epidemiology (broad) | 0.004 | 0.002 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.001 | 0.002 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.004 |
| Insufficient payload (model declined to judge) | 0.010 | 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".