Inivata, EORTC Partner to Study Liquid Biopsy in Assessing Resistance to Pfizer’s Lorbrena

Inivata CEO Clive Morris

Inivata said today it will partner with the European Organisation for Research and Treatment of Cancer (EORTC) to study the company’s InVisionFirst-Lung liquid biopsy test in a Phase II trial designed to screen and monitor anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) patients initiating treatment with Pfizer’s marketed third-generation ALK inhibitor therapy Lorbrena® (lorlatinib).

InVisionFirst-Lung is a ctDNA next generation sequencing liquid biopsy capable of testing 36 genes, including ALK, relevant to the care of patients with advanced NSCLC. The test is available worldwide for both commercial and research use. InVisionFirst-Lung is covered in the U.S. for Medicare patients with advanced (Stage IIIB/IV) NSCLC who meet specific clinical criteria.

In the Phase II trial, dubbed ALKALINE, the primary objective is to assess the progression-free survival rate at 12 months (PFSR12) to lorlatinib in ALK positive advanced NSCLC patients, who progressed on second generation ALK-TKI with the presence of ALK resistance mutations on blood (liquid biopsies) by Independent Central Review (ICR) assessment per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

The ALKALINE trial’s secondary objectives include assessments of:

  • Activity as measured by Overall Response Rate (ORR), Central nervous system response rate (CNS ORR), Duration of the response (DOR), Progression-Free Survival (PFS), Overall Survival (OS).
  • Toxicity of lorlatinib in patients previously treated with 2nd generation ALK TKI
  • Patient reported outcomes (PRO) of global health-related quality of life (HRQOL), functioning and the impact of lorlatinib on disease/treatment-related symptoms of lung cancer.

The trial also includes two exploratory objectives. One entails describing the prevalence of ALK and other molecular alterations in blood ctDNA in patients previously treated with 2nd generation ALK TKI, and activity of lorlatinib in patients previously treated with 2nd generation ALK TKI, as measured by PFSR12, ORR, CNS, ORR, PFS, and OS. The other is describing the concordance between de novo tumour tissue biopsy and blood at the same time point in patients with available tissue biopsy.

InVisionFirst-Lung will be used initially to provide ‘real-time’ data for the pre-trial selection of patients through the detection of molecular resistance, Inivata said. The liquid biopsy test will also provide data on ALK mutational profile in relation to each patient’s response to Lorbrena treatment at the point of disease progression and throughout the course of the study for those patients in whom new ALK mutations are detected.

The first patient will be enrolled at the end of August 2020 and the last patient is set to be treated at the end of June 2023, with study results to be published in a final analysis report at the end of 2024, an Inivata spokesperson told Clinical OMICs.

Eighty-four patients will be involved in the Phase II trial across 30 participating EORTC sites in Belgium, France, Italy, The Netherlands, Norway, Spain, and the United Kingdom.

The trial will be designed to assess mechanisms that promote resistance to Lorbrena, as well as analyze the correlation between ALK resistance mutational profile and response to the drug, Inovata said.

Lorbrena, which won FDA approval last year, is a kinase inhibitor indicated for patients with ALK-positive metastatic NSCLC whose disease has progressed on crizotinib and at least one other ALK inhibitor for metastatic disease; or alectinib as the first ALK inhibitor therapy for metastatic disease; or ceritinib as the first ALK inhibitor therapy for metastatic disease.

While ALK positive NSCLC cancer patients are known to respond well to ALK inhibition therapies such as Lorbrena, that response has been limited in duration due to drug resistance. In addition, the impact of acquired resistance on response to sequential therapies is unknown.

The trial is being sponsored by EORTC, an independent, non-profit research organization in cancer, and funded by Pfizer.

“This pharmaceutical company-backed collaboration highlights the value of our InVision platform in providing rapid and repeatable genomic profiling to enable new analyses of disease and benefit patient treatment,” Inivata CEO Clive Morris said in a statement.

 In an interview with Clinical OMICs earlier this year, Morris said the development and advancement of InVisionFirst-Lung in lung cancer reflected a large unmet need for getting patients to therapy. He cited a study published in 2017 on community oncology in the U.S., which showed that less than 10% of patients were profiled for all FDA-approved drugs, not just investigational treatments.

 “That’s just criminal. People are dying of lung cancer who just aren’t getting these therapies,” Morris observed. “A big part of that is the difficulties with tissue in lung cancer and we can overcome that. ctDNA technologies are here to stay, they are not just hype and hope and then something that disappears. They are actually cementing in clinical practice. Once you do that, then you branch out and find additional uses.”

 EORTC conducts clinical research in cancer, defining new standards of practice for better treatment and care of cancer patients. EORTC network comprises more than 5300 multidisciplinary collaborators in more than 930 hospitals and institutions in 37 countries.

Denis Lacombe, EORTC Director General, added that the trial protocol was developed in the organization’s Methods in Clinical Research workshop, designed to educate early-career investigators on how to develop good clinical trial designs.

“Understanding the patterns of resistance and relapse is one of the most burning challenges in oncology,” Lacombe stated. “EORTC’s scientific strategy, being primarily patient centered, has developed, over the years, a specific focus on programs which address the entire course of the disease taking forward the challenges that patients face at recurrence. We are, therefore, particularly excited with this partnership which brings together the capacity of our organization and new technologies to address the applicability of liquid biopsy for longitudinal studies on this critical question

“Better understanding of resistance will not only provide insight on how to design the next generation of treatment but could also potentially suggest combination treatment to prevent the development of resistance,” Lacombe added.

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