Phase 1b extension study of cancer stemness inhibitor BB608 (napabucasin) administered in combination with FOLFIRI +/- bevacizumab (Bev) in patients (pts) with advanced colorectal cancer (CRC).
Bibliographic record
Abstract
3564 Background: BB608 (aka Napabucasin, BBI-608) is an oral first-in-class cancer stemness inhibitor targeting Stat3-driven gene transcription. Anti-tumor activity was observed in vitro and in vivo. BB608 showed safety and encouraging signs of anti-cancer activity in phase I/II studies. Methods: A phase Ib extension multi-center study in pts with advanced CRC was undertaken to confirm the RP2D and signs of anti-cancer activity of BB608 in combination with FOLFIRI +/- Bev. BB608 was administered continuously at 240 mg BID in combination with FOLFIRI (5-FU 400 mg/m2 bolus with 2400 mg/m2, irinotecan 180 mg/m2, and leucovorin 400 mg/m2 infusion) +/- Bev 5 mg/kg, administered bi-weekly until disease progression, unacceptable toxicity, or other discontinuation criterion. Results: 46 pretreated CRC pts who had failed an average of > 2 prior lines of therapy were enrolled; including 20 pts (43.5%) previously progressed on FOLFIRI +/- Bev. Of the 46 pts, 14 received FOLFIRI and 32 FOLFIRI with Bev in combination with BB608. There was no dose-limiting or unexpected toxicity or significant pharmacokinetic interactions. Most common adverse events (AEs) included grade 1/2 diarrhea, nausea, vomiting and fatigue. Grade 3 AEs observed in 15 pts included diarrhea (9), fatigue (3), dehydration/hyponatremia (1), hypokalemia (1) and burning in rectum (1) resolved with dose reduction and/or supportive care. Disease control (PR+SD) was observed in 37 of 40 evaluable pts (93%), with partial response (PR) in 11 pts (28%) (RECIST 1.1 30-65% regression), and stable disease with tumor regression in 21 pts (53%). Among 19 pts who had progressed on FOLFIRI +/- Bev previously and were evaluable for tumor assessment, disease control (PR+SD) was observed in 17 pts (90%), tumor regression was observed in 15 pts (80%) of which 6 pts achieved PR (32%). Conclusions: This phase Ib extension study confirmed that BB608 can be safely combined with FOLFIRI +/- Bev, and shows encouraging signs of anti-tumor activity in CRC pts, including pts who had previously progressed on FOLFIRI +/- Bev. Clinical trial information: NCT02024607.
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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 | 0.002 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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".