Hypothesis
Maintenance vaccination against telomerase after first-line platinum chemotherapy would extend overall survival in HLA-A*201-positive metastatic NSCLC, since a TERT-specific CD8 response is associated with longer survival.
What failed
Of 221 randomized patients, 190 were analysed; median overall survival was 14.3 months with the vaccine against 11.3 with placebo (p = 0.86), missing the primary endpoint, with time to treatment failure 3.6 versus 3.5 months and no objective responses. Toxicity stayed below grade 3.
Broken assumption
Inducing a TERT-specific immune response in vaccinated patients translates into a survival benefit for the treated population.
Why
The authors point out that the 29.2% of vaccinated patients who mounted a lasting TERT-specific response did live longer (21.3 versus 13.4 months), and argue future work must identify that subgroup in advance.
From the published paper: team et al. British Journal of Cancer, 2020. ↗CC BY