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Pioneer project

A major international research project in lung cancer

Immunotherapy is becoming a game-changer in the treatment of cancers, including one of the most serious: non-small-cell lung cancer (NSCLC). However to date, only 20% of these patients respond favorably to the first available immune-modulating antibodies: PD-1(L1) immune checkpoint inhibitors.

An international team of researchers and clinicians from academia and industry coordinated by Prof. Fabrice BARLESI gave itself 5 years to better understand, predict and overcome these resistances. Laureate of the third “University-Hospital Research in Health” call for projects of the program “Investments for the Future”, this major project, called PIONEER, was launched in November 2017.

Cancer immunotherapy: the beginning of a new story

After targeted therapies at the end of the 90s, immunotherapy today improves the treatment of patients with non-small-cell lung cancer. In that respect, by restoring the ability of patients’ T-cells to recognize and to kill cancer cells, the PD-1(L1) immune checkpoint inhibitors lead to spectacular reduction in tumor volume and a significant lengthening of life expectancy in 20 to 25% of patients.

Despite this progress, lung cancer remains the leading cause of cancer death worldwide (around 1.5 million deaths per year). Indeed, for reasons yet to be fully understood (molecular profile of the tumor, impact of the surrounding microenvironment, the patient’s immune status…), the majority of patients with non-small-cell lung cancer see their cancer progress despite the anti-PD-1(L1) treatment, and to date, no biomarker is able to identify this resistance in advance.

Better understand, predict & overcome anti-PD1(L1) resistance in lung cancer patients

On the initiative of Marseille Immunopôle, Aix-Marseille University (AMU), Inserm and CNRS, four of their research (CIML, CRCM) and technology (CIPHE, MI-mAbs) centers, Assistance Publique-Hôpitaux de Marseille (AP-HM), the Léon Bérard Center in Lyon (CLB), Toulouse Oncopole, the biotechnology company ImCheck Therapeutics, the two French leaders in immuno-oncology Innate Pharma (therapeutic) and HalioDx (diagnostic) and one of the worldwide leaders in the field, the biopharmaceutical group AstraZeneca, have joined forces to take up the main current challenge of immuno-oncology: resistance to PD-1(L1) immune checkpoint inhibitors.

Winner of the 3rd University-Hospital Research in Health call for projects in the “Investments for the Future” program, this project, called PIONEER (Precision Immuno-Oncology for advanced Non-Small Cell Lung Cancer Patients with PD1(L1) ICI Resistance), is coordinated by Fabrice BARLESI, Professor of Medicine at AMU, Head of multidisciplinary oncology and therapeutic innovations department at AP-HM, Coordinator of the Marseille center for early clinical assays in cancer CLIP2 and co-founder of the French cluster of immunotherapy Marseille Immunopôle.

Axes

  • A program of exploratory clinical trials to evaluate the efficacy and safety of new associations of immunomodulatory molecules that target simultaneously several immune checkpoints and cells implicated in the anti-tumoral immune response.
  • The comparative analysis of biological samples taken from patients (blood and biopsy) to identify and validate predictive biomarkers for response to immunotherapy treatments and to develop associated diagnostic tests.
  • The validation of new generation immunomodulatory antibodies on in vivo models of the disease.

Objectives

  • Elucidate the complex mechanisms of resistance to PD-1(L1) inhibitor antibodies ;
  • Develop new therapeutic combinations ;
  • Expand the set of immunomodulatory drugs in lung cancer ;
  • Open up new diagnostic and therapeutic options for these patients.

Key figures

  • 1,825 days
  • 3 countries
  • More than 100 scientists
  • 7 research labs
  • 4 hospitals
  • 25,510,000€ including 8,502,000€ of NRA funding