Michael Barbella, Managing Editor12.12.23
Patient enrollment is continuing in Owlstone Medical's EVOLUTION Phase 2 clinical trial, which aims to support development of a breath test early lung cancer detection.
In the EVOLUTION trial, diagnostic potential of D5-ethyl-ßD-glucuronide (D5-EthGlu) as an exogenous volatile organic compound (EVOC) probe for lung cancer detection is being evaluated. This probe is metabolized by ß-glucuronidase, an enzyme found in the tumor microenvironment around lung cancer cells, into D5-ethanol serving as a unique lung cancer biomarket on exhaled breath. Potential also exists for the test to be used to differentiate benign from malignant lung nodules identified through incidental findings or low dose computed tomography (LDCT) screening.
The Phase 2 clinical trial will assess the test's diagnostic performance and will enable its optimization through testing protocol refinement. Supporting this, the study has been designed to allow differentiation between individuals with lung cancer and relevant contrast groups (e.g. COPD) representative of the clinical populations in which the test is intended to be used. This phase of the trial will recruit up to 150 cases and 200 controls from three sites in Europe and six sites in the United Kingdom. including Royal Papworth Hospital, Cambridge, and Norfolk and Norwich University Hospital, where Professor Eleanor Mishras’ team recruited the first patient.
Previous work has demonstrated the ability to detect D5-ethanol on breath in human cancer xenografted mice and established extracellular ß-glucuronidase presence in tissue samples from early-stage human lung cancers. Phase 1 of the EVOLUTION1 study showed excellent safety and tolerability of the probe, provided guidance on optimal dose and sampling time, and demonstrated in-human proof of mechanism for D5-ethanol release on breath following probe administration in the presence of lung cancers as early as stage 1.2
“The best way to increase the current poor survival probabilities for patients with lung cancer is to detect the disease early when it can be treated with curative intent by surgery or radiotherapy," said Robert Rintoul, professor of Thoracic Oncology, University of Cambridge and Honorary Consultant Respiratory Physician, Royal Papworth Hospital. "Low dose CT (LDCT) for lung cancer screening has been shown to detect more cancers at an early stage, increase survival rates and be cost-effective. An effective breath test for lung cancer could further increase the efficacy, reach and accessibility of lung cancer screening.”
Breath Biopsy represents a new way to determine breath's chemical makeup by measuring volatile organic compounds (VOCs), gaseous molecules that can be sampled quickly and non-invasively. VOCs originate from all body parts as the end product of metabolic processes, making Breath Biopsy applicable to a wide disease range including lung cancer, liver disease, and digestive disease. Breath also contains microscopic aerosol particles from the lungs and airways, which can contain a various biomarkers including for infectious disease. The nature of Breath Biopsy therefore makes it well-suited to addressing two of healthcare's major challenges: early disease detection and precision medicine.
Lung cancer is one of the most common cancers in the world with 2.2 million new cases in 2020, and is a leading cause of death (1.8 million globally in 20203), with five-year survival at 25% in the United States4 and just 15% in the U.K.5 Early diagnosis can greatly improve the clinical outlook as patients diagnosed at an early stage have a 56% five-year survival rate compared to 5% for late stage.6 While there are guidelines in place for the use of LDCT in the United States, and a similar program is being launched in the U.K.,7 uptake is less than 6%8 due to inconvenience, radiation dose, test performance, and in some cases cost. For this reason, there is an acute need for reliable and non-invasive screening solutions, and breath has emerged as a highly promising potential solution.
“Results from Phase 1 of the EVOLUTION trial demonstrated the relevance of the molecular pathway targeted by D5-EthGlu and provided crucial evidence to support further test development," Owlstone Medical Co-Founder/CEO Billy Boyle stated. "With the recruitment of the first patient into Phase 2, we are excited to continue to progress a test that has the potential to transform lung cancer diagnosis by substantially increasing the uptake of testing, leading to more cases of lung cancer being caught early and significantly reducing mortality and costs. Our nodule management test also holds the potential for more effective identification of benign nodules, reducing unnecessary biopsies and surgery.”
Exogenous VOC (EVOC) Probes are a reliable and highly sensitive alternative to endogenous biomarker detection, as is standard in liquid biopsy, which are often found at very low levels and are difficult to detect in early disease. EVOC Probes are engineered to release a volatile reporter on breath after cleavage by a specific target pathway. This approach offers the advantage that compounds not normally found at significant levels in breath can be introduced into the body (individually or as a cocktail) to explore how they are absorbed, metabolized or excreted. Further, high levels can be administered, substantially improving signal-to-noise ratios compared to signals from endogenous sources and thus greatly improving detection reliability.
Owlstone Medical is pioneering breath-based diagnostics by developing and applying Breath Biopsy, a unique platform capable of both biomarker discovery and use in routine clinical testing. The platform includes ReCIVA, a proprietary sample collection device that can take stable breath samples anywhere, the world’s only commercial Breath Biopsy Laboratory located in Cambridge, U.K., and the Breath Biopsy VOC Atlas, an extensive catalogue of identified volatile organic compounds (VOCs) commonly found on breath. The company’s technology is protected by over 140 granted and pending patents and has been used in more than 100 research papers. Owlstone Medical’s research products and services are being deployed at over 100 sites worldwide. Projects are supported by Breath Biopsy OMNI, an advanced solution for reliable end-to-end global breath VOC analysis, which is helping researchers advance biomarker discovery and disease research and maximizing the chances of finding clinically relevant breath biomarkers. The company has a portfolio of Breath Biopsy tests in development for early lung cancer and liver disease detection. In digestive health, under the OMED Health brand, clinical tests for Small Intestinal Bacterial Overgrowth and carbohydrate malabsorption are on market in the U.K., and a handheld device and app for longitudinal monitoring of digestive health is in development.
References
1 https://classic.clinicaltrials.gov/ct2/show/NCT05510674?term=evolution+lung+cancer+evoc&draw=2&rank=1
2 https://www.owlstonemedical.com/about/news/2023/jun/14/owlstone-medical-presents-data-demonstrating-progr/
3 https://www.who.int/news-room/fact-sheets/detail/cancer
4 https://www.lung.org/research/state-of-lung-cancer/key-findings
5 https://www.cancerresearchuk.org/about-cancer/lung-cancer/survival
6 http://www.lung.org/lung-health-and-diseases/lung-disease-lookup/lung-cancer/resource-library/lung-cancer-fact-sheet.html
7 https://www.gov.uk/government/news/new-lung-cancer-screening-roll-out-to-detect-cancer-sooner
8 https://www.lung.org/media/press-releases/state-of-lung-cancer-2022
In the EVOLUTION trial, diagnostic potential of D5-ethyl-ßD-glucuronide (D5-EthGlu) as an exogenous volatile organic compound (EVOC) probe for lung cancer detection is being evaluated. This probe is metabolized by ß-glucuronidase, an enzyme found in the tumor microenvironment around lung cancer cells, into D5-ethanol serving as a unique lung cancer biomarket on exhaled breath. Potential also exists for the test to be used to differentiate benign from malignant lung nodules identified through incidental findings or low dose computed tomography (LDCT) screening.
The Phase 2 clinical trial will assess the test's diagnostic performance and will enable its optimization through testing protocol refinement. Supporting this, the study has been designed to allow differentiation between individuals with lung cancer and relevant contrast groups (e.g. COPD) representative of the clinical populations in which the test is intended to be used. This phase of the trial will recruit up to 150 cases and 200 controls from three sites in Europe and six sites in the United Kingdom. including Royal Papworth Hospital, Cambridge, and Norfolk and Norwich University Hospital, where Professor Eleanor Mishras’ team recruited the first patient.
Previous work has demonstrated the ability to detect D5-ethanol on breath in human cancer xenografted mice and established extracellular ß-glucuronidase presence in tissue samples from early-stage human lung cancers. Phase 1 of the EVOLUTION1 study showed excellent safety and tolerability of the probe, provided guidance on optimal dose and sampling time, and demonstrated in-human proof of mechanism for D5-ethanol release on breath following probe administration in the presence of lung cancers as early as stage 1.2
“The best way to increase the current poor survival probabilities for patients with lung cancer is to detect the disease early when it can be treated with curative intent by surgery or radiotherapy," said Robert Rintoul, professor of Thoracic Oncology, University of Cambridge and Honorary Consultant Respiratory Physician, Royal Papworth Hospital. "Low dose CT (LDCT) for lung cancer screening has been shown to detect more cancers at an early stage, increase survival rates and be cost-effective. An effective breath test for lung cancer could further increase the efficacy, reach and accessibility of lung cancer screening.”
Breath Biopsy represents a new way to determine breath's chemical makeup by measuring volatile organic compounds (VOCs), gaseous molecules that can be sampled quickly and non-invasively. VOCs originate from all body parts as the end product of metabolic processes, making Breath Biopsy applicable to a wide disease range including lung cancer, liver disease, and digestive disease. Breath also contains microscopic aerosol particles from the lungs and airways, which can contain a various biomarkers including for infectious disease. The nature of Breath Biopsy therefore makes it well-suited to addressing two of healthcare's major challenges: early disease detection and precision medicine.
Lung cancer is one of the most common cancers in the world with 2.2 million new cases in 2020, and is a leading cause of death (1.8 million globally in 20203), with five-year survival at 25% in the United States4 and just 15% in the U.K.5 Early diagnosis can greatly improve the clinical outlook as patients diagnosed at an early stage have a 56% five-year survival rate compared to 5% for late stage.6 While there are guidelines in place for the use of LDCT in the United States, and a similar program is being launched in the U.K.,7 uptake is less than 6%8 due to inconvenience, radiation dose, test performance, and in some cases cost. For this reason, there is an acute need for reliable and non-invasive screening solutions, and breath has emerged as a highly promising potential solution.
“Results from Phase 1 of the EVOLUTION trial demonstrated the relevance of the molecular pathway targeted by D5-EthGlu and provided crucial evidence to support further test development," Owlstone Medical Co-Founder/CEO Billy Boyle stated. "With the recruitment of the first patient into Phase 2, we are excited to continue to progress a test that has the potential to transform lung cancer diagnosis by substantially increasing the uptake of testing, leading to more cases of lung cancer being caught early and significantly reducing mortality and costs. Our nodule management test also holds the potential for more effective identification of benign nodules, reducing unnecessary biopsies and surgery.”
Exogenous VOC (EVOC) Probes are a reliable and highly sensitive alternative to endogenous biomarker detection, as is standard in liquid biopsy, which are often found at very low levels and are difficult to detect in early disease. EVOC Probes are engineered to release a volatile reporter on breath after cleavage by a specific target pathway. This approach offers the advantage that compounds not normally found at significant levels in breath can be introduced into the body (individually or as a cocktail) to explore how they are absorbed, metabolized or excreted. Further, high levels can be administered, substantially improving signal-to-noise ratios compared to signals from endogenous sources and thus greatly improving detection reliability.
Owlstone Medical is pioneering breath-based diagnostics by developing and applying Breath Biopsy, a unique platform capable of both biomarker discovery and use in routine clinical testing. The platform includes ReCIVA, a proprietary sample collection device that can take stable breath samples anywhere, the world’s only commercial Breath Biopsy Laboratory located in Cambridge, U.K., and the Breath Biopsy VOC Atlas, an extensive catalogue of identified volatile organic compounds (VOCs) commonly found on breath. The company’s technology is protected by over 140 granted and pending patents and has been used in more than 100 research papers. Owlstone Medical’s research products and services are being deployed at over 100 sites worldwide. Projects are supported by Breath Biopsy OMNI, an advanced solution for reliable end-to-end global breath VOC analysis, which is helping researchers advance biomarker discovery and disease research and maximizing the chances of finding clinically relevant breath biomarkers. The company has a portfolio of Breath Biopsy tests in development for early lung cancer and liver disease detection. In digestive health, under the OMED Health brand, clinical tests for Small Intestinal Bacterial Overgrowth and carbohydrate malabsorption are on market in the U.K., and a handheld device and app for longitudinal monitoring of digestive health is in development.
References
1 https://classic.clinicaltrials.gov/ct2/show/NCT05510674?term=evolution+lung+cancer+evoc&draw=2&rank=1
2 https://www.owlstonemedical.com/about/news/2023/jun/14/owlstone-medical-presents-data-demonstrating-progr/
3 https://www.who.int/news-room/fact-sheets/detail/cancer
4 https://www.lung.org/research/state-of-lung-cancer/key-findings
5 https://www.cancerresearchuk.org/about-cancer/lung-cancer/survival
6 http://www.lung.org/lung-health-and-diseases/lung-disease-lookup/lung-cancer/resource-library/lung-cancer-fact-sheet.html
7 https://www.gov.uk/government/news/new-lung-cancer-screening-roll-out-to-detect-cancer-sooner
8 https://www.lung.org/media/press-releases/state-of-lung-cancer-2022