- The Pioneer Project is the first study to assess over 400 biomarkers for predictive value in advanced non-small cell lung cancers (NSCLC) treated with anti-PD-1/L1 immunotherapy
- Preliminary analysis of the first 100 patients enrolled in the project confirms the importance of ECOG and proportion of PDL1+ tumor cells, but also points towards considering PDL1 expression in other cell types within the tumor, as well as the density of immune cells, both at the periphery and within the tumor, to predict anti-PD1/L1 response and patient survival
- Fabrice Barlesi presents these results at the ESMO 2020 virtual Congress
The Pioneer Project, a major international Hospital-University Research (RHU) project that addresses the critical challenge of resistance to PD-1/L1 immune checkpoint inhibitors (ICIs), today presents a preliminary analysis of its biomarkers study in advanced NSCLC patients at the ESMO 2020 Congress.
Seeking among 400+ agnostic parameters for predictive biomarkers
Immune checkpoint inhibitors have led to a spectacular reduction in tumor volume and a significant lengthening of life expectancy in about 20% of NSCLC patients, and yet, lung cancer remains the leading cause of cancer deaths worldwide as most patients are or become resistant to these treatments. In search of robust biomarkers to predict primary or secondary resistance to PD-1/L1 inhibitors, The Pioneer Project has undertaken the study of >400 comprehensive agnostic and longitudinal biological parameters in advanced NSCLC patients.
The preliminary results presented at ESMO 2020 were obtained under HalioDx’s leadership for the first 100 patients enrolled in the biomarker component of the study. Tumor biopsies and blood samples were drawn before the start and 6 weeks into an anti-PD1/L1 treatment, which the patients received either alone or in combination with chemotherapy. Measured biomarkers included circulating immune cells by FACS, blood soluble factors by ELISA, or immune cells quantification at the tumor site by multiplexed immunohistochemistry coupled to digital pathology.
New promising predictors of response to ICIs
As expected from previous studies, clinical analysis found that the ECOG Performance Status, which reflects a patient’s general health status, is the best predictor of survival following immunotherapy. In terms of biomarkers, and again consistent with previous findings, high levels of PD-L1-expressing cancer cells were predictive of objective response to treatment (determined by the standard RECIST v1.1 response evaluation guidelines), of progression-free survival (PFS) and of overall survival (OS). Interestingly, the density of PD-L1 expressing cells in the tumor, regardless of cell type, also stood out as a potentially robust predictor of patient outcome.
The scientists further found other biomarkers that were associated with improved outcomes. For instance, the density of different immune cells, including cytotoxic T lymphocytes in and around the tumor, but also immuno-suppressive T regulatory cells inside the tumor, appear to have a predictive value of response to treatment.
Figure 1. Examples of potential biomarkers.
“This quantifications and characterization of immune cells and immune factors certainly adds value to known clinical factors in predicting response to ICIs in advanced NSCLC patients”, said Fabrice BARLESI, Coordinator of The Pioneer Project, Professor at Aix-Marseille University, Medical Director of Gustave Roussy and co-founder of the French immunology cluster Marseille Immunopôle. “As the study progresses, additional data from these and other biomarkers will be integrated to draw an “immunogram”, a representation of the status of each patient’s biomarkers that should predict the response to immunotherapy and guide a personalized disease management.”
Figure 2. An immunogram integrates the data obtained from the analysis of a set of relevant biomarkers in each patient to draw their personal profile and ultimately guide therapeutic decision-making.
Finally, the study also looked into the pharmacokinetics of PD-1/L1 inhibitors and revealed a large variability in the circulating levels of these inhibitors among patients that will further be analyzed with respect to disease outcome.
While the biomarker component of The Pioneer Project progresses to understand and predict the resistance to ICIs, an umbrella clinical trial, which includes 4 combination immunotherapies for patients that progress under anti-PD1/L1, is currently recruiting patients, aiming to overcome these resistances.
Precision Immuno-Oncology for advanced NSCLC patients treated with PD(L)1 immune checkpoint inhibitors (ICIs) – An analysis of the first 100 pts from the PIONeeR Project
Fabrice Barlesi, MD, PhD
On behalf of the PIONeeR consortium
Aix-Marseille Université, CNRS, INSERM, Institut Paoli-Calmettes – CRCM, AP-HM, Centre Léon Bérard, InnatePharma, HalioDx, ImCheck Therapeutics, Astra Zeneca, Marseille, France ; Gustave Roussy Cancer Campus, Villejuif, France
Proffered Paper – LBA53 – Monday, Sept 21 – 2:49 – 3:01 PM – Channel 1