Pembrolizumab in combination with the oncolytic virus pelareorep in patients progressing on systemic chemotherapy for advanced pancreatic adenocarcinoma: A phase II study.
Bibliographic record
Abstract
e16789 Background: Pelareorep is an intravenously delivered oncolytic reovirus that can induce a T-cell-inflamed phenotype in pancreatic ductal adenocarcinoma (PDAC). Analysis of tumor tissue from patients treated with pelareorep have shown reovirus replication, T-cell infiltration, and upregulation of PD-L1. We hypothesized that pelareorep in combination pembrolizumab in patients with PDAC would lead to improved response, effective T-cell recognition of tumor antigens and expand peripheral T-cell repertoire. Methods: This investigator-initiated phase II study enrolled PDAC patients who progressed after first-line treatment. Patients received pelareorep at a dose of 4.5x1010TCID50IV on Days 1, 2, 3 & 8of Cycle (C) 1, and Days 1 & 8 with C2 onwards. Pembrolizumab was administered on Day 1 of each 21-day cycle at 200 mg IV. Primary objective was overall response rate (ORR) by RECIST v 1.1 criteria. Secondary objectives included evaluation for reovirus replication and immune analysis in peripheral blood and tumor biopsies. The study was designed using Simon’s two-stage design with 90% power and one-sided alpha = 0.025 to compare 10% vs. 35% ORR. A total of ≥2/11 responses were needed to proceed to stage 2. Results: Thirteen patients were enrolled. Disease control was achieved in 30% of the 12 efficacy-evaluable patients. One patient achieved partial response. Three additional patients achieved stable disease. Treatment was well tolerated, with mostly grade 1 or 2 treatment-related adverse events, including flu-like symptoms. Viral replication was observed in on-treatment tumor biopsies. T-cell receptor sequencing from peripheral blood revealed a high degree of peripheral repertoire turnover and creation of new T-cell clones during treatment. Immune correlation with efficacy analysis is ongoing. Conclusions: Pelareorep with pembrolizumab showed manageable safety profiles and modest efficacy in an unselected PDAC population. The study will not proceed to stage II, however further evaluation of anti-tumor activity of pelareorep and anti-PD-1 therapy is now planned in biomarker defined patients. Clinical trial information: NCT03723915 .
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| 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 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 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".