Efficacy of Nivolumab for Recurrent IDH Mutated High-Grade Gliomas
Status:
Active, not recruiting
Trial end date:
2021-06-01
Target enrollment:
Participant gender:
Summary
Immune checkpoint blockade therapies targeting the immunomodulatory effect of cytotoxic
T-lymphocyte antigen (CTLA-4) and programmed cell death-1/ Programmed death-ligand 1
(PD-1/PD-L1) have recently demonstrated survival benefit and durable response in phase III
trials in several human cancers, especially in tumors that bear high mutation load and/or
tumor-associated neoantigen signatures. The aim of these treatments is to restore effector
T-cell function and antitumor activity, which could be enhanced in the context of high
mutational/neoantigen load. In Isocitrate DeHydrogenase mutated High Grade Gliomas (IDHm
HGGs), acquired resistance to alkylating chemotherapy frequently results from the
inactivation of mismatch-repair (MMR) proteins which in turn leads to the acquisition of a
hypermutator phenotype. These findings suggest that at least in a subset of recurrent IDHm
HGGs immune checkpoint blockade therapies may be particularly effective. IDHm HGGs most
frequently occur in young adults. The first line treatment consists of maximal safe surgical
resection followed by radiotherapy and adjuvant alkylating chemotherapy (Temozolomide or
Procarbazine-CCNU-Vincristine regimen (PCV)). Despite these treatments, most IDHm HGGs
recurred in few years. There is no standard of care at recurrence and the median overall
survival after it is less than 3 years.
The investigators make the hypothesis that treatment with the anti-PD-1 monoclonal antibody
Nivolumab will improve 24 weeks progression-free survival in IDHm HGGs that have recurred
after initial treatment with radiotherapy and alkylating chemotherapy.