Immunization Strategy With Intra-tumoral Injections of Pexa-Vec With Ipilimumab in Metastatic / Advanced Solid Tumors.
Status:
Recruiting
Trial end date:
2022-03-01
Target enrollment:
Participant gender:
Summary
The success of anti-CTLA4 therapy has inaugurated a paradigm shift in oncology where drugs
target the immune system rather than cancer cells in order to stimulate the anti-tumor immune
response. In situ immunization is a strategy where immunomodulatory products such as
pathogens are injected into one tumor site in order to trigger a systemic anti-tumor immune
response. Of importance, pre-clinical rationale has demonstrated that combination of
anti-CTLA4 therapy together with intra-tumoral (IT) oncolytic virus can overcome primary
resistance to systemic anti-CTLA4 therapy. Pexastimogene Devacirepvec (Pexa-Vec) is one of
the new vaccinia oncolytic viruses genetically modified to express GM-CSF. This new and
innovative oncolytic virotherapy should therefore synergize with anti-CTLA4 therapy via
virus-induced tumor cell death & tumor-antigen release, GM-CSF-induced
recruitment/maturation/activation of antigen presenting cells, and anti-CTLA4-induced Treg
blockade/depletion. Intra-tumoral delivery of immunostimulating agents should, therefore,
provide lower toxicity of mAb targeting immune checkpoints. Of note, IT injections of
GM-CSF-encoding oncolytic viruses have already been shown to induce immune-mediated tumor
responses on local (injected) and distant (not injected) tumor sites. In solid injectable
refractory/relapsing metastatic tumors, we make the hypothesis that the addition of Pexa-Vec
to IT ipilimumab (anti-CTLA4 Ab) will overcome primary/secondary resistance to standard
therapy and/or immunotherapy with a better in situ tumor antigen specific T-cell priming. Our
proposal is to conduct a 2-part Phase I clinical trial in order to define the feasibility,
the safety and the anti-tumor effects of intra-tumoral injections of ipilimumab in
combination with the oncolytic virus Pexa-Vec. Dose escalation step will define the MTD and
RP2D of that in situ immunization strategy. Expansion part will assess the anti-tumor effect
of the combination.