NUC-1031 in combination with cisplatin for first-line treatment of patients with advanced biliary tract cancer (NuTide:121).
Bibliographic record
Abstract
TPS602 Background: Biliary tract cancer (BTC) carries a poor prognosis and has no approved treatments. Although gemcitabine + cisplatin (GemCis) is accepted as the global standard of care (SoC) for 1st-line treatment, the reported unconfirmed ORR and OS from randomized studies of this combination are low at 18.5-26.1% and 11.2-11.7 months, respectively. NUC-1031, a phosphoramidate transformation of gemcitabine, is designed to overcome key cancer resistance mechanisms associated with gemcitabine. Promising signs of efficacy have been observed with single-agent NUC-1031 in a Phase I study in advanced solid tumors (Blagden et al 2018) and in the Phase Ib ABC-08 study of NUC-1031 + cisplatin 25 mg/m2 on days 1 and 8 of a 21-day cycle for the 1st-line treatment of advanced BTC. Of 14 patients (pts) enrolled in 2 cohorts (NUC-1031: 625 mg/m2 and 725 mg/m2), 1 pt achieved a CR and 6 pts achieved PR, giving an unconfirmed ORR of 50% and representing an approximate doubling of ORR over SoC. The combination was well-tolerated with no unexpected adverse events or dose-limiting toxicities. The RP2D of NUC-1031 in combination with cisplatin is 725 mg/m2. The tolerability profile together with robust efficacy signals suggested NUC-1031 + cisplatin may represent a more effective therapy than GemCis for BTC and led to initiation of a global Phase III study. Methods: A Phase III, open-label, randomized head-to-head study of NUC-1031 + cisplatin versus GemCis for 1st-line treatment of advanced BTC will include pts ≥18 years with histologically- or cytologically-proven BTC (including cholangiocarcinoma, gallbladder, or ampullary cancer), who have had no prior systemic chemotherapy for locally advanced/metastatic disease. A total of 828 pts will be randomized (1:1) to either 725 mg/m2 NUC-1031 + 25 mg/m2 cisplatin or 1000 mg/m2 gemcitabine + 25 mg/m2 cisplatin, administered on days 1 and 8 of a 21-day cycle. Primary objectives are OS and ORR. Secondary objectives include further measurements of efficacy, safety, pharmacokinetics, and patient-reported quality of life. The study will be conducted at approximately 120 sites across North America, Europe and Asia Pacific countries. Clinical trial information: NCT04163900.
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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 | 0.000 | 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) | 0.004 | 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".