Adaptive organoid-based precision therapy study in pancreatic cancer (ADOPT): A phase II single-arm study to evaluate the efficacy of patient-derived organoid (PDO)-directed therapy in advanced pancreatic ductal adenocarcinoma (PDAC).
Bibliographic record
Abstract
TPS4232 Background: PDAC is a devastating malignancy. High-throughput genomic technologies have yielded insights regarding the molecular underpinnings and heterogeneity of PDAC. Systemic treatment options are limited to cytotoxic chemotherapies, except for approx. 10%, who receive targeted treatment based on genomic profiling. PDO’s are three-dimensional ex vivo experimental models grown directly from tumor tissue and can provide a direct assessment of drug response. By directly exposing cancer cells to potential drug therapies, functional profiling provides a dynamic measurement of response that is more informative than static gene panels. PDOs can theoretically be used to direct therapeutic decisions, offering an opportunity to expand the reach of precision therapies for PDAC beyond genomics. To date, PDO testing has been limited by small sample sizes, few drugs included in the screens, and retrospective studies. To expand the impact of precision therapy, we developed a rapid high-throughput screening (HTS) platform where over 3,000 drugs can be tested in PDOs within 8-10 weeks of diagnosis. In ADOPT, we aim to formally investigate the efficacy of PDO-directed therapy in a prospective phase II study, leveraging our existing platforms using real-time HTS of PDOs . This study represents one of the first formal trials of PDO-directed therapy in solid tumors. Our novel approach will enroll pts with advanced PDAC who do not have alternative treatment options. Methods: This is an actively recruiting prospective, single-arm phase II trial. Patients (pts) with advanced epithelial PDAC are eligible if they either: 1) progressed on, were intolerant to, or refused first-line or subsequent therapies (Cohort A), or 2) have stable disease after ≥8 cycles of FOLFIRINOX (“Maintenance” Cohort B) and have a PDO showing sensitivity to an approved HC drug. Pts will be recruited, from multiple ongoing studies including PROSPER-PANC where we have successfully generated and tested a PDO. PDO-directed treatment will be selected based on drug sensitivity as tested through our validated HTS platform. Each case will be discussed at our PDO dedicated tumor board. All pts must meet the inclusion/exclusion and drug-specific eligibility criteria. The primary endpoint is disease control rate. A Simon’s two-stage optimal design will be used to test the hypothesis: H0: P ≤ 0.05 versus H1: P ≥ 0.25. In the first stage, 9 pts will be evaluated. The trial will be discontinued if no disease control response is observed in this stage. If at least one response is observed, then the trial will continue to the second stage and an additional 17 pts will be evaluated for a total of 26 evaluable. This design has a one-sided alpha of 0.05 and power of 80%. We will reject the null hypothesis after 26 if 3 or more responses are observed. Clinical trial information: awaited .
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 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) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.003 |
| 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".