Aglatimagene Besadenovec (CAN-2409): Phase 3 Benefit Now Backed by Evidence of Lasting Immune Remodeling

The story around aglatimagene besadenovec (CAN-2409) has become more interesting. The phase 3 PrTK03 trial had already shown that adding this locally injected viral immunotherapy to radiotherapy improved disease-free survival in men with intermediate- to high-risk localised prostate cancer. New biomarker data now provide a biological explanation for that benefit: the treatment appears to leave the tumour microenvironment immunologically altered for more than two years.
PrTK03 was a randomised, placebo-controlled phase 3 trial in which patients received radiotherapy with either aglatimagene or placebo.
After injection into the prostate and administration of valacyclovir, infected tumour cells convert the antiviral drug into toxic nucleotide analogues, causing immunogenic cell death and releasing tumour antigens that can potentially stimulate an antitumour immune response.

The new analysis used AI-assisted digital pathology on prostate biopsies collected before treatment and again more than two years later. Among the evaluable samples, aglatimagene significantly increased the overall lymphocyte fraction compared with radiotherapy alone. In patients who still had residual tumour, the effect was even clearer: there was a greater fraction of lymphocytes inside tumour regions, greater enrichment of lymphocytes around tumour cells, and significantly more direct mixing between immune and tumour cells.
This is particularly notable because the immune changes were still detectable more than two years after only three intraprostatic injections. Earlier pathology data had already shown that post-treatment biopsies were negative in 80% of evaluable patients treated with aglatimagene versus 63% of controls. In the intermediate-risk subgroup specifically, negative biopsies were seen in 76.6% versus 60.7%.
There is also early evidence that the response may not remain confined to the prostate. In the ongoing PrTK05 study, serial blood samples showed expansion of CD8 effector and effector-memory T cells, cells that were actively multiplying and cells equipped to kill tumor cells after local aglatimagene treatment.
The numbers are still very small , 13 treated patients and 6 controls , and formal comparisons are ongoing, but the findings raise the possibility that a local treatment is generating a broader systemic immune response.
The clinical data are also becoming more mature. With median follow-up of 58 months, patients with intermediate-risk disease had a 41% reduction in the risk of prostate-cancer recurrence or prostate-cancer-specific death, with HR 0.59. Exploratory analyses also favoured aglatimagene for time to biochemical failure, metastasis and salvage therapy, although these harder endpoints still involve relatively few events and should be interpreted cautiously.

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