The Phase 2 clinical trial will analyze blood-based biomarkers versus conventional radiography for cancer patients treated with immunotherapy; findings could change direction of lung cancer treatment
The Cancer Research Institute (CRI) and The Mark Foundation for Cancer Research have launched an innovative clinical trial that aims to demonstrate the utility of a novel, ultra-sensitive biomarker-directed blood test, or liquid biopsy, in assessing cancer patient responses to immunotherapy. If this and future studies show that this approach can more accurately characterize these responses to therapy, oncologists may gain a new and more reliable, less costly, and less invasive means to help them identify earlier in a cancer patient’s treatment course whether immunotherapy may be effective or whether other therapeutic options may offer a better alternative.
The phase 2, multi-center trial will be conducted by the Canadian Cancer Trials Group (CCTG) with clinical investigators at five sites in Canada and at John Hopkins University in the United States. Valsamo Anagnostou, M.D., Ph.D., assistant professor of Oncology, director of the Thoracic Oncology Biorepository and a Swim Across America investigator at the Johns Hopkins Kimmel Comprehensive Cancer Center is the study’s chair.
In the trial’s first stage, investigators will explore whether distinct dynamic changes in levels of circulating cell-free tumor DNA (ctDNA) associated with patterns of clinical response or resistance to immunotherapy are superior to radiographic response assessments. Liquid biopsies from patients in the trial will be analyzed by Personal Genome Diagnostics (PGDx). In the trial’s second stage, investigators will prospectively examine whether these patterns can effectively guide treatment decisions for patients with non-small cell lung cancer, currently the leading cause of cancer deaths worldwide. In the second stage of the study, ctDNA analysis will be used to determine whether a patient should receive immunotherapy alone or in combination with chemotherapy.
“This novel clinical trial exemplifies the power of science-driven collaboration directed by the CRI Anna-Maria Kellen Clinical Accelerator, which brings together industry, academic, and nonprofit partners to address critical unanswered questions in immuno-oncology and expand immunotherapy’s benefits to more patients,” said Vanessa M. Lucey, Ph.D., MBA, director of CRI’s Venture Fund and Clinical Accelerator. “We are excited to partner for the first time with The Mark Foundation for Cancer Research as well as continue our ongoing clinical research partnerships with CCTG and PGDx, who together are working with CRI to design, fund, and carry out this important study.”
“We are committed to catalyzing liquid biopsy projects because of the technique’s transformative potential to ensure patients have the best chance to receive therapies that will be effective for them,” said Michele Cleary, Ph.D., CEO of The Mark Foundation for Cancer Research. “The results of this team’s work could eventually change how clinical studies are conducted and decisions about patient treatments are made.”
“Accurately assessing who may be benefiting from treatment is challenging, especially for immunotherapy as the change in tumor size may not reflect the anti-cancer effect. This trial will identify whether testing blood for evidence of tumor DNA correlates with patient benefit. If so, it can lead to better assessment of patient status, whether patients are benefiting from treatment or should consider a different treatment and result in fewer imaging tests and exposure to X-rays,” said Janet Dancey, M.D., FRCPC, director of the Canadian Cancer Trials Group.
Building on a groundbreaking study
Evidence of ctDNA as a clinically relevant dynamic biomarker for assessment and prediction of cancer patient responses to immunotherapy was recently first demonstrated in a groundbreaking paper published last March in the journal Cancer Research. Lead author Anagnostou and colleagues showed that post-treatment changes in ctDNA levels reliably predicted later clinical responses.
Specifically, Anagnostou and her team reported that patients whose ctDNA levels fell after receiving immunotherapy had better clinical responses, whereas patients whose ctDNA levels remained unchanged or increased responded poorly or not at all. Importantly, ctDNA measurement allowed for a more accurate prediction of patient responses up to 8.7 weeks earlier on average than is possible with current conventional CT imaging.
Key industry and academic partners
This clinical trial is the second to result from the collaboration formed in 2018 between CRI and CCTG, a Canada-based cooperative oncology group that is sponsoring the study. It is also the second CRI Clinical Accelerator trial to leverage in-kind support from industry partner PGDx, which is supplying centralized analysis of patient-derived liquid biopsies.
About the trial
Title: Study of Molecular Response Adaptive Immuno-Chemotherapy in Patients With NSCLC (NCT04093167)
- Vancouver Cancer Centre (Canadian Study Chair: Cheryl Ho, M.D., FRCPC)
- CancerCare Manitoba
- Juravinski Cancer Centre at Hamilton Health Sciences
- The Ottawa Hospital Research Institute
- University Health Network Princess Margaret Cancer Centre
- Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University (Study Chair: Valsamo Anagnostou, M.D., Ph.D.)
Canadian Cancer Trials Group: Lisa Gallinaro, Study Coordinator,