Heat shock protein peptide complex-96 vaccination for newly diagnosed glioblastoma:
a phase I, single-arm trial
https://insight.jci.org/articles/view/99145 (open access)
The survival results of this trial are worth remarking upon.
20 newly diagnosed GBM patients received standard treatments plus HSPPC-96 vaccine (also known as Prophage, under development in the USA by Agenus). All had total tumor resections, and the majority had MGMT unmethylated tumors and were IDH1 wild-type.
19 of the 20 were evaluable for efficacy. Median survival for the entire group was 31.4 months. I've seen only a couple of other small trials (vaccine trials involving complete or near complete tumor resection) with efficacy outcomes comparable to this.
Clear efficacy of the vaccine was shown by tumor specific immune responses (TSIR) being increased on average by 2.3-fold after vaccination, and the fact that those with "high" TSIR (TSIR above the median) had not reached median survival (> 40.5 months), while those with low TSIR (below the median) had median survival of only 14.6 months, showing vaccine efficacy in only a subset of patients. Median PFS are unremarkable (11 months median for the entire group, 12.3 months for the high TSIR group), but immune-related pseudoprogression could have been a factor in dropping PFS values.
Compared to the phase 2 trial published by Bloch et al. in 2017, https://www.ncbi.nlm.nih.gov/pubmed/28193626
the Chinese trial had worse PFS outcomes but better survival outcomes, also suggesting that pseudoprogression may have been a factor in the Chinese trial.
Additionally, patients with MGMT-methylatated tumors had far better outcomes in the Bloch et al. trial, but in this Chinese trial, 14 out of 16 tested tumors were MGMT unmethylated.
A trial is currently underway testing pembrolizumab with or without HSPPC-96 vaccine, and I would expect the combination therapy to improve even further on the efficacy results of the vaccine.
https://clinicaltrials.gov/ct2/show/NCT03018288
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