A phase I open-label study to evaluate safety, tolerability and pharmacokinetic (PK) profile of VB4–845, an anti-EpCAM immunotoxin, in subjects with SCCHN
Bibliographic record
Abstract
5539 Background: Head and neck cancer is the sixth most common cancer accounting for ∼5% of newly diagnosed malignancies in North America. VB4–845 is a fusion protein engineered from the fusion of a truncated form of Pseudomonas Exotoxin A to a humanized scFv specific for the epithelial cell adhesion molecule, Ep-CAM. Ep-CAM is highly expressed on carcinoma cells of epithelial origin, with limited normal cell expression. VB4–845 targets and kills Ep-CAM-positive tumors. A phase I trial was completed to determine the the maximum tolerated dose (MTD) and the pk profile of intratumoural injected drug in patients with advanced SCCHN. Methods: Dose escalation was completed using modified Fibonacci increments with a minimum 3 subjects per dose level. VB4–845 was administered over 5 consecutive days by intratumoral injection at escalating dose levels of 20, 40, 80, 130, 200, and 280 μg. After a 23 day rest, a 2nd cycle of drug was given at each dose level. In subjects with more than one lesion, the most accessible lesion ≤ 5 cm in any greatest dimension was injected (indicator/target lesion). All toxicities were assessed according to the NCI CTC v3. Blood samples were collected at different times in the study to determine pk and to assess immunogenicity of VB4–845. Results: VB4–845 safety profile was positive as no DLTs were observed. Only mild treatment-related side-effects, such as injection site pain were noted. Pk analysis of VB4–845 injected intratumoral showed the drug to have a clearance rate of 3–4hrs. Most patients developed an anti-VB4–845 with most of the response being directed against the toxin. Independently-verified clinical responses were observed in 43% of the patients with Ep-CAM-positive tumors; 2 significant regressions and 4 minor regressions. Four other patients with Ep-CAM-potive tumors had stable disease for an overall tumour growth control rate (objective responses plus stable disease) of 71%. Conclusions: VB4–845 was safe at all dose levels tested suggesting that higher dose levels can be explored. Moreover, clinical endpoints indicate that even under phase I testing conditions, VB4–845 treatment is efficacious against Ep-CAM-positive SCCHN tumors. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Viventia Biotech Viventia Biotech
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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 | 0.000 |
| 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 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 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".