A Phase 1 Clinical Study of Intravenous Administration of PV701, an Oncolytic Virus, Using Two-Step Desensitization
Why this work is in the frame
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Bibliographic record
Abstract
PURPOSE: In a previous phase 1 study, adverse events, especially flu-like symptoms, were observed mainly following the first i.v. bolus dose of PV701, an oncolytic Newcastle disease virus. Desensitization to adverse events of subsequent doses occurred, allowing a 10-fold increase in the maximum tolerated dose for these doses. Although one-step desensitization (a single desensitizing dose with higher subsequent doses) addressed the tolerability of high repeat doses, additional testing was required to further improve tolerability of the initial dose. This study tested the hypothesis that two-step desensitization, using two dose increments before high repeat doses, would be well tolerated. EXPERIMENTAL DESIGN: Sixteen adults with incurable solid tumors were enrolled. Cycles consisted of six PV701 doses over 2 weeks followed by a 1-week rest. Doses 1 to 2 were 1 and 12 x 10(9) plaque-forming units (pfu)/m(2), respectively, whereas doses 3 to 6 were escalated by cohort from 24 to 120 x 10(9) pfu/m(2). RESULTS: No dose-limiting toxicities were observed, permitting dose escalation through cohort 4 (1, 12, 120, 120, 120, 120 x 10(9) pfu/m(2)). Mild flu-like symptoms were common following the first infusion, diminished with repeated dosing, and were less pronounced than those seen previously. Tumor regression was observed in a patient with anal carcinoma who enrolled with stable disease following palliative radiotherapy. Four patients with clearly progressing cancer before enrollment had disease stabilization of >/=6 months. CONCLUSIONS: This novel two-step desensitization improved patient tolerability compared with the previous regimen. Toxicities were predictable and manageable. PV701, the first oncolytic virus to enter phase 1 i.v. testing, continues to show single-agent activity, warranting planned phase 2 trials.
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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 | 0.006 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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 it