VCN-01 plus chemotherapy shows mixed survival results in metastatic pancreatic cancer

A randomized phase 2b trial published in Nature Medicine evaluated intravenous zabilugene almadenorepvec (VCN-01), a hyaluronidase-expressing oncolytic adenovirus, with gemcitabine and nab-paclitaxel versus chemotherapy alone in first-line metastatic pancreatic ductal adenocarcinoma. The intent-to-treat population included 101 patients: 53 assigned to the combination and 48 to chemotherapy. Primary endpoints included overall survival in the intent-to-treat and full analysis set populations, plus safety and tolerability.

Median overall survival in the intent-to-treat population was 10.6 versus 8.6 months (HR 0.69, 95% CI 0.42–1.12; P=0.196). Median progression-free survival was 5.6 versus 4.6 months (HR 0.63; P=0.046). In the full analysis set, comprising 48 patients per group, median overall survival was 10.8 versus 8.6 months (HR 0.57, 95% CI 0.34–0.96; P=0.055). Investigators reported that this met the primary efficacy endpoint; the supplied text does not explain the statistical threshold underlying that conclusion.

Duration of response was 11.2 versus 5.4 months, with no statistically significant differences in overall response or disease control rates. VCN-01-related events included pyrexia, flu-like symptoms, elevated liver enzymes and decreased platelet counts; serious events occurred in 22.6% of patients. Two fatal events, one per group, were considered unrelated to treatment.

The findings suggest activity but do not establish a survival benefit across analysis populations. The small phase 2b study warrants blinded phase 3 confirmation, and interpretation requires clarification of the full analysis set endpoint criteria.