View source for Agenus Prophage (Heat-Shock Protein Peptide Complex-96) Vaccine

{{TreatmentInfo
|drug_name=Agenus Prophage (Heat-Shock Protein Peptide Complex-96) Vaccine
|FDA_approval=In clinical trials; not yet FDA-approved
|used_for=Recurrent heavily pretreated glioblastoma multiforme (GBM) and newly diagnosed GBM
|clinical_trial_phase=Phase II
|common_side_effects=Not explicitly detailed; similar immunotherapy treatments often include flu-like symptoms, injection site reactions, fatigue
|OS_without=Historical controls suggest a median survival time of 6 months for recurrent GBM
|OS_with=Median survival of 42.6 weeks (~9.8 months) in recurrent GBM; Median survival of 23.8 months in newly diagnosed GBM when combined with the Stupp protocol
|PFS_without=Typically less than 7 months for newly diagnosed GBM under standard treatment
|PFS_with=17.8 months for newly diagnosed GBM, possibly the longest PFS seen in a phase II trial for GBM
|usefulness_rating=4
|usefulness_explanation=The vaccine shows promise, especially in extending progression-free survival in newly diagnosed GBM. It offers a novel approach by leveraging the patient's immune system, potentially improving outcomes in a disease with few effective treatments.
|toxicity_level=2
|toxicity_explanation=While specific side effects are not detailed, similar vaccines have been associated with manageable side effects like flu-like symptoms, suggesting a relatively low toxicity level.
|book_text=A variation in the use of dendritic cells first subjected tumor tissue to a heat-shock
treatment to elevate the expression of heat-shock proteins, which were extracted from the
blood and incubated with dendritic cells from individual patients. In a clinical trial (163)
conducted at UCSF and Columbia for patients with recurrent heavily pretreated tumors,
the vaccine produced a median survival of 42.6 weeks (about 9.8 months), which
compares favorably to the 6-month survival time for historical controls, and is
comparable to the 9-11 months when Avastin is used with patients with recurrent tumors.

A subsequent news release from Agenus, Inc, a biotech company sponsoring the research,
reported the results of phase II clinical trial in which the heat-shock dendritic vaccine was
combined with the standard Stupp protocol (164). Median progression-free survival was
17.8 months and median survival was 23.8 months. This median progression-free
survival of 17.8 months is perhaps the longest PFS yet seen in any
substantially sized phase 2 trial for newly diagnosed glioblastoma.

Follow-up data (reference 339, abstract 2011) presented at the ASCO 2015 conference
revealed that patients with high PD-L1 expression (the ligand for the PD-1 immune
checkpoint on the surface of immune cells which is the target for the therapeutic
antibodies nivolumab and pembrolizumab) had a median survival of 18 months, while
those with low expression of PD-L1 had a median survival of 44.7 months. This finding
suggests that efficacy of the heat shock protein peptide vaccine could be greatly improved
by co-administration of PD-1 antibodies such as nivolumab or pembrolizumab.

|links=https://delta.larvol.com/Products/?ProductId=2a41421b-2069-4661-ab62-7631bc4eb36d, https://synapse.patsnap.com/drug/9269a1e8dda548e9babb2434396151ed
}}