A phase 1b/2 study of amcasertib, a first-in-class cancer stemness kinase inhibitor, in advanced adenoid cystic carcinoma.
Bibliographic record
Abstract
6036 Background: Amcasertib (BBI-503) is an oral first-in-class cancer stemness kinase inhibitor. By targeting multiple serine-threonine stemness kinases, amcasertib inhibits Nanog and other cancer stemness pathways. A phase I clinical trial of amcasertib demonstrated safety and signs of anti-cancer activity in patients (pts) with advanced solid tumors. Cancer stemness pathways have been implicated in adenoid cystic carcinoma (ACC). An RP2D expansion cohort was opened for patients with ACC. Methods: Pts with metastatic, unresectable ACC for whom systemic therapy was indicated were enrolled. Amcasertib was administered orally, once or twice daily, in continuous 28-day cycles at a starting dose of 110 mg to 300 mg total daily. Adverse events were categorized according to CTCAE v4.03 and tumor imaging was evaluated per RECIST 1.1 guidelines. Results: 14 pts with ACC were enrolled. Prior treatments included surgery and radiation in all pts (100%), while 57% (n = 8) had received prior systemic therapy (average 2 prior lines, range 1 to 4). Treatment with amcasertib was well tolerated, with grade 3 diarrhea reported in 1 patient and no related grade 4 AEs. The disease control rate (DCR, proportion with stable disease at 8-weeks, partial response, or complete response per RECIST) was 86% (n = 12) with prolonged disease control (≥ 6 months) achieved in 57% (n = 8) patients. At 12 months, 79% of pts were alive. Median overall survival (mOS) was 28.3 months. Conclusions: Clinical safety and encouraging signs of anti-cancer activity were observed in pts with advanced ACC who received treatment with amcasertib. Long term follow-up demonstrates prolonged duration of disease control and that a majority of pts in this cohort have survived beyond 2 years. Further clinical evaluation of amcasertib in pts with ACC is warranted. Clinical trial information: NCT01781455.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.006 | 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".