Prediction of response to pelareorep plus pembrolizumab in pancreatic ductal adenocarcinoma (PDAC).
Bibliographic record
Abstract
e15726 Background: Pelareorep is an oncolytic reovirus that can induce an inflamed T-cell-infiltrated (hot) phenotype in PDAC. In a phase Ib trial, pelareorep was administered in combination with pembrolizumab and chemotherapy in patients (pts) with advanced, pre-treated PDAC. The safety profile was acceptable and efficacy results were encouraging (Mahalingam ASCO GI 2018). Here we present the results of immune analysis in peripheral blood. Methods: Peripheral blood mononuclear cells (PBMCs) were collected on cycle 1 day 1 (C1D1, pre-pelareorep), C1D8 (pre-pembrolizumab) and C2D1 (pre-pelareorep). RNA from PBMCs was analyzed using a customized Nanostring panel. The research-use only immunoSEQ Assay (Adaptive Biotechnologies, Seattle, WA) was used to characterize T-cell receptors from PBMCs. Results: Eleven pts were enrolled. Disease control was achieved in 50% of the 6 efficacy-evaluable pts. One pt achieved PR that lasted 17.4m. Two additional pts achieved SD, lasting 277 and 126 days. Downregulation (relative change < -1.5) of CD1b (C1D1), HLA-C, MAPK14 (C1D8), CD63, LY96, LTF, TXK, TNFSF13, IL25, C1QB (C2D1) and upregulation ( > 1.5) of IL17F (C1D1), MAGEA4, CCL7 (C1D8), CSF1, ICOS, LILRA4, TICAM2 (C2D1) was observed in pts with clinical benefit vs. no clinical benefit (raw p < 0.05). Increase in clonal diversity was noted during therapy overall (Table). C2D1 had significantly more clonal expansion than C1D8; ~30% of expanded clones from C1D8 were also expanded at C2D1 (durable). High numbers of early expanded (C1D8 only) and durable clones were associated with longer survival. Conclusions: Pts with disease control had higher baseline IL17F compared to non-responders. On-treatment relative decrease in IL25 (Th2), increase in LILRA4, TICAM2 (antiviral response) and ICOS were noted in these pts. There was new clone expansion after treatment overall; ~30% of expanded clones at C1D8 were durable. Early and durable clonal expansion correlated with survival. A phase II trial with pelareorep plus pembrolizumab in advanced PDAC is ongoing. Clinical trial information: NCT02620423. [Table: see text]
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 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 | 0.002 |
| 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 | 0.000 |
| 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".