Theriva Biologics’ VCN-01, an oncolytic virus therapy for advanced pancreatic cancer, showed mixed results in a Phase IIb trial published in Nature Medicine. The modified adenovirus targets tumor cells by replicating inside them and degrading hyaluronic acid, a thick barrier in pancreatic ductal adenocarcinoma (PDAC) that blocks drug delivery and immune access. Researchers tested VCN-01 alongside standard chemotherapy, gemcitabine and nab-paclitaxel, in 112 patients with untreated metastatic PDAC. Eleven participants withdrew before treatment began, leaving 101 in the intent-to-treat (ITT) group: 53 received the combination therapy, while 48 got chemotherapy alone.
The ITT analysis found no statistically significant improvement in overall survival (OS). Patients on VCN-01 had a median OS of 10.6 months, compared to 8.6 months for those on chemotherapy alone, with a hazard ratio of 0.69 and a P-value of 0.196. However, progression-free survival (PFS) did show a meaningful difference. The combination therapy extended PFS to 5.6 months, versus 4.6 months with chemotherapy (HR 0.63, P=0.046).
A stricter evaluation, the full analysis set (FAS), altered the findings. This group excluded 11 patients who failed to meet dose requirements, leaving 48 in each arm. Five of those exclusions came from the VCN-01 group, all of whom had received inadequate chemotherapy to assess the full treatment effect. In the FAS, median OS increased slightly to 10.8 months, with a P-value of 0.055, just above the trial’s prespecified 0.10 threshold for significance. PFS improved further, reaching 7.0 months in the combination arm compared to 4.6 months (HR 0.55, P=0.011).
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Beyond survival metrics, the data revealed potential long-term benefits for some patients. At 15 months, 35.5% of those treated with VCN-01 were still alive, compared to 12.8% in the control group. By 18 months, the survival gap widened to 31.1% versus 8.5%. While overall response rates did not differ significantly between groups, patients on VCN-01 experienced longer-lasting tumor responses, a median duration of 11.2 months versus 5.4 months (HR 0.22, P=0.004).
The trial’s design introduced challenges that complicate interpretation. Theriva Biologics set a 0.10 significance cutoff, which is less rigorous than the conventional 0.05 standard. Additionally, excluding patients after randomization, even when prespecified, can introduce bias, particularly in a study of this size. The results do not conclusively prove VCN-01’s benefit, but they suggest the therapy may extend survival for certain patients when combined with chemotherapy.
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The exclusion of patients after randomization, while prespecified, raises concerns about bias in a small trial. Removing nearly 10% of the experimental group could disproportionately influence survival estimates, particularly when event timing varies. These factors leave the trial’s primary outcome open to interpretation, requiring further validation in a larger study.
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