A phase 1b study of the cancer stem cell inhibitor BBI608 administered with paclitaxel in patients with advanced malignancies.
Bibliographic record
Abstract
2530 Background: BBI608 is an oral first-in-class cancer stemness inhibitor which inhibits the Stat3, β-catenin and Nanog pathways. Preclinically, potent, broad-spectrum anti-tumor and anti-metastatic activity was observed in vitro and in vivo, alone and in combination with other agents. BBI608 with paclitaxel showed marked synergy in vivo. In a phase I study, BBI608 monotherapy was well tolerated with encouraging signs of anti-tumor activity and a RP2D of 500 mg BID. Methods: A phase Ib dose-escalation study in patients with advanced cancer was undertaken to determine safety, tolerability, RP2D, and preliminary anti-cancer activity of BBI608 plus weekly paclitaxel. BBI608 was administered in 3 escalating dose cohorts (200 mg BID, 400 mg BID, 500 mg BID) in combination with paclitaxel (80 mg/m2 weekly; 3 of every 4 weeks) until progression of disease, unacceptable toxicity, or other discontinuation criteria was met. Results: 24 patients were enrolled. The BBI608 monotherapy RP2D could be given in combination with paclitaxel in full dose. MTD was not determined. No new adverse events were observed, and the safety profile was similar to that of each agent as monotherapy. The most common adverse events included grade 1 and 2 diarrhea, abdominal cramps, nausea, vomiting. Grade 3 events related to protocol therapy occurred in 4 patients and included diarrhea, dehydration, and weakness. No significant pharmacokinetic interactions were observed. Disease control (CR+PR+SD) was observed in 10 of 15 (67%) evaluable patients. Of 5 patients with refractory gastric/GEJ adenocarcinoma enrolled, 2 had PR (48% and 45% regressions), 1 had SD with 25% regression, and 2 (who failed prior taxane) had prolonged SD ≥ 24 wks. Tumor regression or SD ≥ 16 wks was also seen in patients with platinum-resistant ovarian cancer (1 of 2), melanoma (2 of 3), bladder CA (1 of 3) and NSCLC (1 of 1). Conclusions: This phase Ib study demonstrated that BBI608 and weekly paclitaxel can be safely combined at full dose. Encouraging anti-tumor activity was observed across several tumor types, particularly in patients with gastric and GEJ adenocarcinoma. Clinical trial information: NCT01325441.
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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 | 0.003 | 0.001 |
| 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".