- The disease
- Advanced or metastatic solid tumours is a broad category covering cancers that have spread beyond their original site and are not amenable to curative surgery. The NCT05346484 trial enrolled adults with a range of solid tumour types, including cholangiocarcinoma (bile duct cancer) (per ClinicalTrials.gov NCT05346484). A separate, smaller Phase 1 study (NCT05081492) focused specifically on metastatic triple-negative breast cancer, a subtype defined by the absence of three common hormone receptors (per ClinicalTrials.gov NCT05081492). Both studies targeted patients who had already received prior therapy.
- What the asset is trying to do
- CF33/VAXINIA (CF33-hNIS) is an oncolytic virus, meaning it is an engineered virus designed to infect and replicate selectively in cancer cells. The CF33 backbone has been modified to express hNIS (human sodium-iodide symporter), a protein that can concentrate iodine, which may allow imaging of virus spread and potentially enable radioiodine-based treatment (per ClinicalTrials.gov NCT05346484). The NCT05346484 study tested CF33-hNIS both as a standalone agent and in combination with pembrolizumab, a checkpoint inhibitor that blocks the PD-1/PD-L1 immune-suppression pathway, as well as with modified FOLFOX chemotherapy (per ClinicalTrials.gov NCT05346484). A related construct, CF33-CD19, expressed a CD19 surface marker on infected tumour cells to potentially make them visible to CD19-directed T-cell therapies (per ClinicalTrials.gov NCT06063317).
- What the trial is measuring, and why it matters
- The primary focus of Phase 1 studies is safety: identifying dose-limiting toxicities and establishing a safe dose range (per ClinicalTrials.gov NCT05346484). Secondary measures typically include preliminary signals of anti-tumour activity such as objective response rate (the proportion of patients whose tumour shrinks by a defined threshold) and duration of response. In the triple-negative breast cancer study, the primary endpoint was safety and tolerability (per ClinicalTrials.gov NCT05081492). Understanding how the virus distributes and replicates in vivo may also be assessed given the hNIS imaging capability.
- Efficacy benchmarks in this setting
- In advanced or metastatic solid tumours more broadly, approved checkpoint inhibitors such as pembrolizumab have demonstrated objective response rates that vary substantially by tumour histology and biomarker status; for example, in advanced cholangiocarcinoma, pembrolizumab monotherapy showed an objective response rate of approximately 5.8% in previously treated patients in the KEYNOTE-158 study (Marabelle et al, Journal of Clinical Oncology, 2020). In metastatic triple-negative breast cancer, the combination of pembrolizumab plus chemotherapy in PD-L1-positive patients showed a progression-free survival benefit versus chemotherapy alone in the KEYNOTE-522 trial (Schmid et al, New England Journal of Medicine, 2022). Any efficacy figures from early Phase 1 cohorts of CF33/VAXINIA are not statistically comparable to these approved-therapy benchmarks, as Phase 1 studies are not powered or designed to establish efficacy.