Preliminary phase 2 results of ABT-751 in subjects with advanced renal cell carcinoma (RCC)
Bibliographic record
Abstract
4603 Background: There is currently no effective adjuvant therapy available for subjects with advanced RCC. ABT-751, an oral antimitotic agent that binds to the colchicine site of β-tubulin and prevents microtubule polymerization, has shown antitumor activity in various human xenograft models. In addition, signs of antitumor activity, consisting mainly of stable disease, were seen in subjects with RCC during phase 1 ABT-751 studies. Methods: This phase 2, open label, multi-center study evaluated safety and efficacy of ABT-751 in subjects with advanced RCC [N = 97: 43 subjects with no prior therapy (NPT), 54 subjects with prior therapy (PT)]. For each cycle, subjects received 200 mg ABT-751 orally once daily for 21 consecutive days followed by a 7-day break. Cycles were repeated until the subject met discontinuation criteria. Safety was assessed by adverse events (AEs) and laboratory evaluations. Time to progression (TTP) was analyzed using Kaplan-Meier methodology. Tumor response was assessed radiographically every 2 cycles using RECIST. Results: The median duration of therapy was 2 cycles (range 1 - 10). AEs were reported in 94/97 subjects, and 31/97 (32%) subjects experienced serious adverse events (SAEs). The most commonly reported AEs were asthenia (69%), constipation (59%), nausea (46%), and anorexia (44%). The most common Grade 3 or 4 AEs considered possibly or probably related to drug were asthenia (7%) and ileus (7%). The most common SAEs were carcinoma (6%) and ileus (6%). Thirteen subjects experienced SAEs considered possibly related to study drug, and the most common were ileus (5%) and diarrhea (2%). The median TTP was 3.8 months (95% CI = 3.6 - 4.1). One partial response was observed, and the subject is ongoing in Cycle 9. Two other subjects are experiencing minor responses (26% and 22% decrease in target lesions; ongoing in Cycles 6 and 9, respectively). To date, 17 subjects have had stable disease for 8 or more cycles (12 NPT and 5 PT), the longest duration being nearly one year. Conclusions: The 21-day dosing regimen appears to have an acceptable safety profile in phase 2 clinical trials. Prolonged stable disease and tumor responses suggest a potential benefit from ABT-751 therapy. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Abbott Laboratories Abbott Laboratories
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| 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 | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".