A phase II, multicenter, open-label study of YM155 plus docetaxel in subjects with stage III (unresectable) or stage IV melanoma.
Bibliographic record
Abstract
8587 Background: Survivin is a microtubule-associated protein implicated in both preservation of cell viability and regulation of mitosis in tumor cells. It is over-expressed in melanoma, breast, and non-Hodgkin’s lymphoma. YM155 is a first in class survivin inhibitor. Methods: The study had 2 parts: Part 1 established the dose of docetaxel that was tolerable in combination withYM155 at 5 mg/m2/day continuous infusion over 168 hours q 3 weeks. Part 2 utilized the dose of docetaxel established in Part 1 to further evaluate the tolerability and activity of the combination. The primary endpoint was 6-month progression-free survival (PFS). Secondary endpoints were overall response rate, 1-year overall survival (OS), time from first response to progression, clinical benefit rate, time to response, and safety. Results: 64 patients with metastatic melanoma were treated with docetaxel followed by continuous infusion YM155. 7 patients were treated with 100mg/m2 of docetaxel and 57 patients were treated with 75mg/m2 of docetaxel. Median age was 59, with 44 men and 20 women treated. 6-month PFS per Independent Review Committee (IRC) was 34.8% (95% CI 21.3 – 48.6%). Overall objective response rate per IRC was 12.5%, with no complete responses (CR) and 8 patients with partial responses (PR). The Stable disease (SD) rate was 51.6%, leading to a clinical benefit rate (CR + PR + SD) of 64.1%. Estimated 1-year overall survival is 50.5%. 87.5% of patients experienced a Grade 3 (G3) or Grade 4 (G4) event attributable to either YM155 or docetaxel. The clinically pertinent G3 or 4 toxicities occurring in greater than 5% of patients treated included neutropenia (59.4%), febrile neutropenia (12.5%), mucositis (9.4%), fatigue (7.8%), diarrhea (6.3%), and dehydration (6.3%). There were 3 deaths on study, all attributable to disease progression. Conclusions: YM155 is a novel agent that shows modest activity when combined with docetaxel in patients with melanoma. YM155 was generally well tolerated, but the pre-determined primary endpoint for efficacy was not achieved.
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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) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| 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".