Research Triangle Park, NC, USA and Cambridge, UK, 20 January 2021 – Inivata, a leader in liquid biopsy, today announces that the first patients have been tested using InVisionFirst®-Lung as part of the Phase II ALKALINE trial sponsored by the European Organisation for Research and Treatment of Cancer (EORTC). As part of the study Inivata’s InVisionFirst-Lung liquid biopsy will be used to test and monitor ALK positive non-small cell lung cancer (NSCLC) patients initiating treatment with lorlatinib, Pfizer Inc.’s third generation ALK inhibitor therapy.

The aim of this academic trial, announced in 2019 and being supported by Pfizer, is to examine the resistance to lorlatinib in ALK positive NSCLC patients. While in the past these patients were known to respond well to ALK inhibition therapies, such as lorlatinib, drug resistance in patients has been increasing. This trial is designed to provide insights for clinicians and researchers to better understand resistance mechanisms, and to analyze the correlation between ALK resistance mutational profile and response to lorlatinib. A total of 100 patients will be involved in two study designs run in parallel across 30 participating EORTC sites across Europe.

The Phase II study is a single arm, multicenter study. InVisionFirst-Lung will be used to provide data on ALK mutational profile following progression to second generation TKI’s, prior to lorlatinib treatment. This mutational profile will be correlated with lorlatinib treatment outcome after 12 months. In addition, each patient’s response to lorlatinib treatment at the point of disease progression will be monitored using ctDNA profiling for new ALK mutations or other resistance mechanisms. This study will help clinicians to understand which patient populations are more likely to benefit from lorlatinib treatment and may also inform further treatment strategies.

InVisionFirst-Lung is also being used to provide longitudinal assessment for the sub-study selection of patients through the detection of molecular resistance at the time of disease progression to second generation TKIs. This will inform on the time of emergence of ALK and other resistance mutations and the relevance of liquid biopsy monitoring for clinical outcomes.

Clive Morris, Chief Executive Officer of Inivata, commented: “This is a positive step forward in our collaboration with the EORTC, as we work together to unlock insights which will help us improve patient treatment in cases of drug resistance, an increasing global health challenge. Inivata’s involvement in this study highlights the value of the InVision® platform in optimizing patient recruitment in trials and providing rapid and repeatable genomic insights to researchers, and more broadly supports the utilization of liquid biopsy technology in clinical settings.”

Laura Mezquita, MD PhD, Department of Medical Oncology, Hospital Clinic, Barcelona, and co-PI of ALKALINE trial, commented: “It is of vital importance that clinicians gain a better understanding of the patterns of resistance to drug therapies in cancer treatment, where time is of the essence in ensuring the best outcomes for patients. We hope that this study will not only provide insights on how to adjust existing treatment regimens to make them more effective for patients, but could also assist in the development of combination treatments, which would prevent this build-up of resistance in the first place.” 

Professor Anne-Marie Dingemans, MD PhD, Professor of Pulmonology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam and Senior PI of ALKALINE trial, said: “Using Inivata’s InVisionFirst-Lung liquid biopsy in this trial will enable us to test and closely monitor patients throughout the course of the study with high confidence in the accuracy of the data. By learning which patients are more responsive to lorlatinib, we hope that the findings of this study will be able to help clinicians to make better informed decisions for their patients.”