766 A clinical trial to evaluate the safety, tolerability and preliminary efficacy of VG161 in combination with Nivolumab in patients with advanced pancreatic cancer
Bibliographic record
Abstract
Background VG161 is a non-attenuated HSV-1 Oncolytic virus (OV) with IL-12, IL-15, IL-15Ra and PD-L1 blocking payloads. Here we report an open label, study to evaluate the safety, pharmacokinetics (PK), and biologic effects of VG161 in patients (pts) with advanced pancreatic cancer progressed after standard of care. The study is actively recruiting. NCT05162118. Methods Dose escalation follows a 3+3 design at 3 dose levels as VG161 intratumoral injections on days 1,2,3 and Nivolumab treatment on days 22 and 28 of each 28 days treatment cycle. PK and viral shedding (DNA), samples from biopsies, blood, urine, and swabs from injection site and other anatomical locations were analyzed by PCR. Changes of cytokines and lymphocyte subsets in blood were also observed as pharmacodynamic parameters. Samples were harvested on C1D1, C1D7 and C2D1 which were analyzed by single-cell sequencing. Results As of 31 May 2023, 13 pts received doses of 1.5x108 PFU, 2.0x108 PFU and 3.0x108 PFU. 10 males and 3 females with the median age of 58 years were enrolled. 76.9% were PD(L)1 refractory,46.2% had 2 Prior lines of therapy and 13% ≥3. No Dose Limiting Toxicities were observed. Any grade treatment-related AEs (TRAEs) was 5.7%. The most common TRAEs were all grade 1 and 2. 9 pts had SAEs, including 1 pts (7%) with a related SAE (cytokine release syndrome). No TRAEs leading to dose reduction and treatment discontinuation. No pts had positive viral shedding. 11 pts were efficacy evaluable; ORR 9.1% and DCR 23.1% based on RECIST v1.1. Tumor shrinkage was also observed in non-injected lesions demonstrating an abscopal effect. According to the results of single cell data analysis, patients with advanced pancreatic cancer treated with VG161 remodeled the tumor microenvironment in the tumor, torqued from a cold tumor to a hot tumor, reduced the number of tumor cells, and significantly increased T and NK cell infiltration (T cells increased by 15% in injected lesions and NK cells increased by 3% in non-injected lesions after VG161 dosing). Moreover, patients were also more sensitive to subsequent immunosuppressive therapy. Conclusions VG161 can significantly improve the immune microenvironment and provide favorable conditions for the combination of nivolumab. Trial Registration NCT05162118 Ethics Approval Approval Letter of Clinical Research Ethics Committee of the First Affiliated Hospital, College of Medicine, Zhejiang University. ID:IIT20210108C
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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 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".