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

2016-12-01 16:08:22 | BioPortfolio


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.


The study is a proof of concept, open label, multicentric, 2-parts, Phase I dose escalation trial. In dose selection part (any histological types except HCC), patients will be treated with an IT boost injection with Pexa-Vec (fixed dose of 1x109 pfu / injection ) alone at Week 1 followed by IT injections of Pexa-Vec + ipilimumab (up to 4 dose levels) at Weeks 3, 5 and 9. The dose escalation part will follow a classical 3+3 design. 3 to 6 patients will be enrolled at each DL (Dose Level) depending of the number of Dose Limiting Toxicity (DLT) observed. At the end of each DL cohort, a teleconference (Dose escalation meeting) will be organized with the sponsor, in order to select the dose for the next cohort. In Expansion cohorts ( up to 3 cohorts) patients will be treated with an IT boost injection with Pexa-Vec alone (fixed dose of 1x109 pfu / injection) at Week 1 followed by IT injections of Pexa-Vec + ipilimumab (RP2D) at Weeks 3, 5 and 9. In both parts, the treatment with both IMPs should be continued as per protocol until Withdrawal of consent, Disease progression as per irRC (immune related response criteria), General or specific changes in the patient's condition that render the patient unacceptable for further treatment in the judgment of the investigator, Pregnancy or Unacceptable adverse events(s) including DLTs.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment


Metastatic Tumor


Pexa-Vec, Ipilimumab


Centre Léon Bérard


Not yet recruiting


Centre Leon Berard

Results (where available)

View Results


Published on BioPortfolio: 2016-12-01T16:08:22-0500

Clinical Trials [1915 Associated Clinical Trials listed on BioPortfolio]

A Study of Recombinant Vaccinia Virus in Combination With REGN2810 for Renal Cell Carcinoma

This is a Phase 1b, open-label, multi-center, dose-escalation trial of Pexa-Vec plus REGN2810 in patients with metastatic or unresectable renal cell carcinoma (RCC). The trial consists of ...

Phase II Randomized Trial of Ipilimumab Versus Ipilimumab and Radiotherapy in Metastatic Melanoma

An attractive area of research regards immune manipulations to recover some of the patient's immune response to his/her tumor, a strategy that has the advantages of being both natural and ...

A Study Investigating SGI-110 in Combination With Ipilimumab in Unresectable or Metastatic Melanoma Patients

Thi pahse I, dose-escalation trial will determine the MTD, safety and the additional benefit achieved from adding SGI-110 to ipilimumab therapy in metastatic melanoma patients. Preclinical...

A Phase 2, Multicenter Study of FOLFIRINOX Followed by Ipilimumab With Allogenic GM-CSF Transfected Pancreatic Tumor Vaccine in the Treatment of Metastatic Pancreatic Cancer

This study will enroll patients who have metastatic pancreatic cancer with stable disease on FOLFIRINOX chemotherapy. The main purpose of this study is to compare survival between patient...

Nivolumab With or Without Ipilimumab in Treating Patients With Metastatic or Unresectable Sarcoma

This randomized phase II trial studies how well nivolumab with or without ipilimumab works in treating patients with sarcoma that has spread from the primary site to other parts of the bod...

PubMed Articles [7440 Associated PubMed Articles listed on BioPortfolio]

Nivolumab Plus Ipilimumab Has Antitumor Activity in Metastatic RCC.

Nivolumab plus ipilimumab achieves durable responses and has manageable safety in metastatic RCC.

Ipilimumab-associated cholestatic hepatitis: a case report and literature review.

Ipilimumab is a monoclonal antibody that exerts its effects by inhibiting the cytotoxic T-lymphocyte-associated protein 4 receptor on cytotoxic T lymphocytes. It is frequently used for the treatment o...

Development of Bell's Palsy After Treatment With Ipilimumab and Nivolumab for Metastatic Melanoma: A Case Report.

Ipilimumab is a human monoclonal antibody that targets cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), and it is FDA approved for the treatment of unresectable or metastatic melanoma. Immune-rel...

 Therapy: Consensus Statement From the Faculty of the Melanoma Nursing Initiative on Managing Adverse Events With Ipilimumab Monotherapy and Combination Therapy With Nivolumab.

Ipilimumab (Yervoy®) therapy improves outcomes in patients with resected stage III melanoma, and ipilimumab alone or combined with nivolumab (Opdivo®) does so in those with unresectable or metastati...

Phase II study of ipilimumab in adolescents with unresectable stage III or IV malignant melanoma.

Ipilimumab is approved for the treatment of advanced melanoma in adults; however, little information on the efficacy and safety of ipilimumab in younger patients is available.

Medical and Biotech [MESH] Definitions

Mucocellular carcinoma of the ovary, usually metastatic from the gastrointestinal tract, characterized by areas of mucoid degeneration and the presence of signet-ring-like cells. It accounts for 30%-40% of metastatic cancers to the ovaries and possibly 1%-2% of all malignant ovarian tumors. The lesions may not be discovered until the primary disease is advanced, and most patients die of their disease within a year. In some cases, a primary tumor is not found. (From Dorland, 27th ed; Holland et al., Cancer Medicine, 3d ed, p1685)

A member of the family of TISSUE INHIBITOR OF METALLOPROTEINASES. It is a 21-kDa nonglycosylated protein found in tissue fluid and is secreted as a complex with progelatinase A by human fibroblast and uncomplexed from alveolar macrophages. An overexpression of TIMP-2 has been shown to inhibit invasive and metastatic activity of tumor cells and decrease tumor growth in vivo.

A lipoxygenase metabolite of ARACHIDONIC ACID. It is a highly selective ligand used to label mu-opioid receptors in both membranes and tissue sections. The 12-S-HETE analog has been reported to augment tumor cell metastatic potential through activation of protein kinase C. (J Pharmacol Exp Ther 1995; 274(3):1545-51; J Natl Cancer Inst 1994; 86(15):1145-51)

Primary or metastatic neoplasms of the CEREBELLUM. Tumors in this location frequently present with ATAXIA or signs of INTRACRANIAL HYPERTENSION due to obstruction of the fourth ventricle. Common primary cerebellar tumors include fibrillary ASTROCYTOMA and cerebellar HEMANGIOBLASTOMA. The cerebellum is a relatively common site for tumor metastases from the lung, breast, and other distant organs. (From Okazaki & Scheithauer, Atlas of Neuropathology, 1988, p86 and p141)

Hypoxic conditions in tumor cells due to the tumor outgrowing its blood supply. It is associated with increased METASTASIS and resistance to RADIOTHERAPY and DRUG THERAPY.

More From BioPortfolio on "Immunization Strategy With Intra-tumoral Injections of Pexa-Vec With Ipilimumab in Metastatic / Advanced Solid Tumors."

Quick Search

Relevant Topics

  Bladder Cancer Brain Cancer Breast Cancer Cancer Cervical Cancer Colorectal Head & Neck Cancers Hodgkin Lymphoma Leukemia Lung Cancer Melanoma Myeloma Ovarian Cancer Pancreatic Cancer ...

Cancer Disease
Cancer is not just one disease but many diseases. There are more than 100 different types of cancer. Most cancers are named for the organ or type of cell in which they start - for example, cancer that begins in the colon is called colon cancer; cancer th...

Allergies Automimmune Disease Human Papillomavirus (HPV) Immunology Vaccine Immunology is the study of immunity and the defence mechanisms of the body. A greater understanding of immunology is needed to develop vaccines, understand ...

Searches Linking to this Trial