A phase 1 dose-escalation study of BBI503, a first-in-class cancer stemness kinase inhibitor in adult patients with advanced solid tumors.
Bibliographic record
Abstract
2527 Background: Targeting cancer stem cells (CSC) may hold significant therapeutic promise. BBI503 is an orally-administered first-in-class multi-kinase inhibitor with potent activity against CSC. Preclinically, potent anti-CSC and broad-spectrum anti-tumor and anti-metastatic activity was seen in vitro and in vivo. Methods: A first-in-man phase 1 dose escalation studyin patients with advanced cancer was conducted to determine safety, tolerability, RP2D, pharmacokinetics and preliminary anti-tumor activity of BBI503. BBI503 was given orally, continuously, in 28-day cycles until disease progression, unacceptable toxicity, or other discontinuation criteria were met. Results: Escalating doses from 10 mg to 450 mg once daily were administered to 26 patients. MTD was not reached. BBI503 was well tolerated, with mild GI adverse events, including grade 1, 2 diarrhea, abdominal cramping, nausea, anorexia. Grade 3 diarrhea was observed in 2 subjects at 450 mg once daily. BBI503 exhibited favorable pharmacokinetics with dose-dependent increases in plasma concentration up to 300 mg once daily. Inhibition of cancer stem cell markers was observed in biopsied tumor tissues. Of 20 evaluable patients, 11 (55%) had stable disease (SD) with a median time to progression of 16 wks. Of those patients with SD, tumor regression and/or prolonged stable disease (≥ 16 weeks) were observed in 10 (50% of all enrolled patients) (see Table). Clinical trial information: NCT01781455. Diagnosis Number of patients evaluable Number of patients with minor regression or SD ≥ 16 wks. Colorectal cancer 5 3 Head and neck cancer 2 2 Hepatocellular carcinoma 2 1 Renal cell carcinoma 1 1 Gastric/GEJ adenocarcinoma 1 1 Pancreatic neuroendocrine 1 1 Non-small cell lung cancer 1 1
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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 teacher head, 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".