Summary
A randomized phase 2b trial compared the oncolytic adenovirus VCN-01 plus chemotherapy with chemotherapy alone as first-line treatment for metastatic pancreatic cancer. Progression-free survival was longer in the VCN-01 group, while overall-survival results differed between the trial’s analysis populations.
A randomized, open-label phase 2b trial found longer median progression-free survival when the oncolytic adenovirus VCN-01 was added to gemcitabine and nab-paclitaxel (GnP) as first-line treatment for metastatic pancreatic ductal adenocarcinoma. The overall-survival results depended on which trial population was analysed: the study authors reported that the primary overall-survival endpoint was met in the full analysis set, while the intent-to-treat comparison did not show a statistically significant difference.
The trial enrolled 101 patients in the intent-to-treat population: 53 received VCN-01 plus GnP and 48 received GnP alone. In the full analysis set, there were 48 patients in each group. VCN-01 is an engineered adenovirus that expresses hyaluronidase. The enzyme breaks down hyaluronan, a component of the extracellular matrix; the treatment is intended to pair the virus’s oncolytic activity with an effect on the tumour’s surrounding tissue.
What the trial found
In the intent-to-treat population, median overall survival was 10.6 months with VCN-01 plus GnP and 8.6 months with GnP alone. The hazard ratio was 0.69 (95% confidence interval 0.42–1.12; P=0.196). A hazard ratio below 1 favours the combination in this comparison, but the reported confidence interval includes 1 and the P value was not statistically significant.
In the full analysis set, median overall survival was 10.8 months with the combination and 8.6 months with GnP alone. The article reports that the primary efficacy endpoint was met in this population, with a hazard ratio of 0.57 (95% CI 0.34–0.96; P=0.055). The difference between the two population analyses is important when interpreting the survival finding.
Progression-free survival—the time before cancer worsened or the patient died—was longer in both analyses. In the intent-to-treat population, medians were 5.6 versus 4.6 months (HR 0.63; 95% CI 0.40–1.00; P=0.046). In the full analysis set, they were 7.0 versus 4.6 months (HR 0.55; 95% CI 0.34–0.88; P=0.011). Among patients whose cancer responded, median duration of response was 11.2 months with VCN-01 plus GnP and 5.4 months with GnP alone (HR 0.22; 95% CI 0.08–0.63; P=0.004). The study found no statistically significant between-group differences in overall response rate, disease control rate or CA 19-9 levels.
Safety and the next evidence step
Reported VCN-01-related events included fever, flu-like symptoms, increased liver enzymes and lower platelet counts. Serious events occurred in 22.6% of patients. One fatal event occurred in each treatment group, and neither was considered related to study treatment.
The results provide randomized clinical evidence for adding VCN-01 to GnP, but come from a phase 2b study. Theriva Biologics supported the trial, provided the study drug and operational support, and was involved in its design, data collection, analysis and decision to publish, as disclosed in the article. The authors say the findings warrant evaluation in a blinded phase 3 trial.