Early results of the PASS-01 trial: Pancreatic adenocarcinoma signature stratification for treatment-01.
Bibliographic record
Abstract
LBA4004 Background: Over 60% of patients with pancreatic ductal adenocarcinoma (PDAC) present with metastatic disease. Both modified FOLFIRINOX (mFFX) and gemcitabine/nab-paclitaxel (GnP) are first-line options in advanced PDAC, however have not been compared prospectively in North American patients. Moreover, biomarkers to guide selection are lacking. Basal-like and Classical subtypes are prognostic, but their predictive impact is unknown. Patient-derived organoids (PDOs) are now feasible to study for drug pharmacotyping. Expedient molecular profiling with additional PDO drug sensitivities could enable better precision choices in PDAC. Methods: PASS-01 is a multi-center randomized phase II trial evaluating the benefit of 1 st line mFFX vs GnP in de novo metastatic PDAC patients with ECOG PS 0-1, (germline BRCA1/2, PALB2 excluded) who have baseline tumor biopsies (bx) for whole genome/transcriptional sequencing (WGTS) and PDO generation/pharmacotyping with standard and novel drugs. The primary endpoint is the PFS of mFFX vs GnP (received at least 1 dose of assigned chemo, per protocol (PP)), 136 patients needed to reach 80% power to detect a difference in median PFS of 7 vs 5 months between mFFX and GnP at significance level of 0.3 in a 2-sided test. Secondary endpoints include: ORR, SAEs, OS, impact of RNA signatures and GATA6 expression on outcomes. Each patient is discussed at a molecular tumor board immediately following their 1 st 8-week CT with the goal of recommending precision 2nd-line treatment options on progression. Results: This trial accrued 160 pts between 09/20 and 01/24, 45% in Canada, 55% in US with 140 eligible for 1 st line PFS, data lock Mar 1/24 (see table). Median PFS (PP) was 5.1 mo for GnP and 4.0 mo for mFFX (p=0.14). Best response PR/SD for GnP: 29/45% and 24/35% for mFFX. SAEs attributed to the study were 3% GnP, 13% mFFX and 0.7% bx. Median OS (ITT) was 9.7 mo with GnP and 8.4 mo with mFFX, p=0.04. Of 113 patients in the PP analysis with progression, 64 (57%) received 2nd-line treatment (GnP, n= 30, mFFX n=34) Of these, a correlate-guided approach was delivered in 32 (50%), including 21 (66%) receiving chemo and 11 (34%) receiving a targeted or immunotherapy regimen. Correlative studies are underway. Preliminary analysis shows >80% successful whole genomes and >72% RNA signatures. PP patients include 9 % KRAS wild-type and 21% Basal-like PDAC. PDO-drug models have been established in 50%. Conclusions: Upfront multi-omic profiling of PDAC can be successfully incorporated into a multicenter randomized trial. While we have observed PP improved PFS and ITT longer OS favouring GnP in this cohort without gBRCA 1/2 or PALB2m, the benefit of chemo for advanced PDAC patients remains poor, with 43% unable to receive 2 nd line, arguing strongly for the development of 1 st -line biomarker selected strategies. Clinical trial information: NCT04469556 . [Table: see text]
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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 | 0.004 | 0.003 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.002 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.006 | 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".