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Immunization Strategy With Intra-tumoral Injections of Pexa-Vec With Ipilimumab in Metastatic / Advanced Solid Tumors.

NCT02977156 · Status: COMPLETED · Phase: PHASE1 · Type: INTERVENTIONAL · Enrollment: 22

Last updated 2022-07-25

No results posted yet for this study

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.

Conditions

  • Metastatic Tumor
  • Advanced Tumor

Interventions

BIOLOGICAL

Pexa-Vec

IT Injections will be performed by a radiologist using imaging-guidance, ultrasound or computed tomography (CT). The dose to be injected could be divided between 1 to 5 tumor lesions.

DRUG

Ipilimumab

IT Injections will be performed by a radiologist using imaging-guidance, ultrasound or computed tomography (CT). The dose to be injected could be divided between 1 to 5 tumor lesions.

Sponsors & Collaborators

  • Transgene

    collaborator INDUSTRY

  • Centre Leon Berard

    lead OTHER

Principal Investigators

  • Aurélien MARABELLE, MD, PhD · Centre Leon Berard

Study Design

Allocation
NA
Purpose
TREATMENT
Masking
NONE
Model
SINGLE_GROUP

Eligibility

Min Age
18 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2017-01-03
Primary Completion
2022-04-13
Completion
2022-06-06

Countries

  • France

Study Locations

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Entities

Drugs

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT02977156 on ClinicalTrials.gov