Meet our new ECMC Network Lead, Professor Gary Middleton

05 Mar 2024
The ECMC has recently recruited Professor Gary Middleton to the role of ECMC Network Lead. Gary is a medical oncologist who specialises in lung cancer and colorectal cancer. Gary is Director of the Birmingham ECMC and Lead for the Birmingham CRUK Clinical Academic Training Programme. A key interest in stratified approaches to patient treatment, Gary has a strong presence in UK stratified medicine clinical trials. We spoke to Gary to find out a bit more about his initial thoughts on the role.
What are you most passionate about in your work?
I am an academic clinician in a 50:50 role. In spite of becoming a consultant before some of the attendees at the recent JING meeting were born, I still really enjoy the patient contact. There is no other medical discipline where in the course of a single clinical hour one is thinking about and trying to apply yet another scientific, translational or clinical advance whilst at the same time offering symptom control alongside emotional and psychological support to people with cancer and their loved ones at this most vulnerable of times. This is a great privilege and the rapport you develop with those you try and care for is truly unique. This experience intimately informs my research. At present this revolves around 3 main areas: predictive biomarkers for severe immune related adverse events, understanding the mechanisms, and how to target them, and how to more effectively target squamous lung cancer.
I am also passionate about supporting the future generation, and working with my PhD students, many of whom are clinical, during and beyond their PhD studies, is arguably my greatest academic pleasure and one I most certainly get out of bed for in the morning. Running the local Clinical Academic Training Programme is a true passion. 
What do you think are the biggest opportunities for the ECMC network to make a real difference to the early phase research environment/to patients?
The unique collective intellectual power, clinical trials expertise, experience and scientific knowledge of the ECMC network must be harnessed to tackle the significant current challenges in oncology. We should continue to grow the Network’s role as a globally important tissue and age agnostic co-operative group recognised by our pharma partners as a natural venue for their entire early phase pipelines and a powerhouse to design a suite of translationally rich early phase trials and answer globally relevant translational questions.  
Collaboration is essential, and we need to function as a truly co-operative network that actively approaches industry to try and negotiate access to their entire early phase pipeline, on a proffered provider basis. This effort absolutely must be thoroughly informed and co-developed by those with lived experience of cancer, who are crucial to shaping the questions that are relevant to them. 
Within the translational research space, what would you like to see the Network achieve in your first 12 months? 
The Network’s translational expertise and broader collective wisdom represents a unique opportunity to generate novel trial concepts, through an ECMC Translational Research Forum to focus on:
(i) Using this Forum as a Target Assessment Panel, at which novel targets or co-targeting approaches identified pre-clinically are prioritised and the appropriate biomarker programme relevant to that target developed to allow us to actively approach industry partners with the aim to obtain the best in class agents or to inform novel drug design efforts. 
The vision is to leverage both industry finance but also generate high quality grant applications based on the wealth of Network-wide scientific and clinical expertise rather than of that of a single investigator. We simply have the to ensure through this group that the significant UK funding in basic science in specific areas of unmet need are fully leveraged to inform the design of a next wave of phase I trials. To improve outcomes we must move the science to the bedside and the ECMC network can be the vehicle to drive this transition.
(ii) Capitalising on the experience, reach, and expertise of this Forum as a route to provide advice on biomarker-led activity. Specifically, advising on the right translational technologies and questions which must be incorporated into trial design. We must avoid failure at late phase by ensuring we have an excellent and tissue-relevant understanding of the pharmacodynamics of trialled agents at the early phase. 
How do you believe we can leverage the potential of the Network and its portfolio of trials to further drive impact and improve patient outcomes?
Through the ECMC network the translational work of the Network’s trials should continue to seek, amongst other more fundamental questions about cancer biology, supplemental biomarkers of exceptional response versus primary progression in a more contextualised precision medicine that looks for greater precision, and which will allow us to more adequately manage expectations of people with cancer and their loved ones treated with apparently the right treatment for their particular cancer.
Our network serves a large and highly diverse population and yet collaborative efforts using real world evidence (RWE) leveraging this is lacking. We have fallen behind, particularly the US, in this space and we urgently need widespread deep genomic testing to be available as standard of care and extensive collaboration to achieve the sample size necessary to power the analyses. As an ECMC network, we must work to triage the key translational questions of network-wide relevance and to generate grant applications to fund such studies co-authored by a highly expert national collaborative consortium which will then mobilise its network to provide the samples and technical capacity and expertise to answer these questions. The clinical, scientific and technical excellence of the ECMC working as a collaborative group combined with its patient population can place us at the forefront of the delivery of practice changing and highly clinically relevant translational science. The ECMC can become a crucible of big translational science harnessing big data to answer big questions.
The Network also has a key role in ensuring the UK remains a top European destination for clinical research. Currently a critical limiting factor in delivering on the full promise of the network is the challenge associated with setting up and conducting research in a system as complex as the NHS. Addressing operational delivery concerns including accelerating study start up, increased use of technology in trial delivery (e.g. decentralised trials) and creating transparent and appropriate delivery metrics will be important not just in retaining our global position but in improving it.
Underwriting every single one of these initiatives is that they must impact wholly for the well-being of all people affected by cancer. Membership of historically marginalised communities and/or those living in conditions of socio-economic deprivation can both present barriers not only to clinical trial entry but also to cancer screening, genomic testing and cancer therapy itself. We need to ensure we use the national reach of the ECMC network to begin to address this key issue. 
What do you see as some of the most pressing challenges currently facing the oncology research environment? 
The steady decline in oncologists with strong research backgrounds is a huge concern given that a scientific training provides crucial tools to develop discovery, translational and clinical research programmes in cancer and to introduce novel technologies into clinical practice. Early last year Baroness Brown stated, “the clinical research environment in the NHS is on a dangerous precipice”. She stated that clinical academics “bring the latest medical understanding to the frontline of clinical care, such as genomic medicine leading to innovations in cancer treatment.” Oncology is no exception to this worrying dearth of future academics. 
The maintenance of a steady flow of clinical academics and clinician scientists is fundamental to the future of experimental cancer medicine in the UK. Initiatives such as the ECMC JING (Junior Investigators Network Group) and CRUK’s Clinical Academic Training Programmes are exemplars of how to build cohort identity and support and drive the oncology research agenda from the earliest stages of the development of ECRs. It will be essential to leverage the impact these initiatives are having to develop a pipeline of engaged and enthusiastic researchers for the future. 
How can the ECMC network position itself to improve equity of access to clinical research?
Working with the Programme Office we plan to identify and break down the barriers resulting in a lack of diversity in clinical trials and to propose meaningful solutions to enhance equality, diversity and inclusion. This work will look at the relevance to early phase cancer trials of recently published toolkits that attempt to capture a representative and equitable sample in health research and recommendation guidelines aimed at improving Equality, Diversity and Inclusion (EDI) in clinical trials. Centres and individuals across the Network are already heavily engaged in this space at multiple intersecting levels and the Network initiatives must be informed by these activities. The importance of this critical endeavour has been beautifully described by ASCO/ACCC as: “removing barriers to enrolment and participation for people historically under-represented in clinical trials is a critical scientific and ethical imperative for the cancer community”.
Besides the obvious ethical issues around unrepresentative referral for phase I trials, there are scientific and clinical reasons that this is unacceptable as I have already mentioned, but also deeper moral reasons. We have seen from work delivered by Cancer Research UK, and others that socio-economic deprivation limits referral to and benefit from clinical trials and yet is a major driver of cancer development and of the co-morbidities that allow effective treatment of these cancers. We intend to bring the Network together to address and begin to reverse this awful situation. We will also consider how best the collective ECMC voice can influence and advise on wider UK-wide discussion on this important issue.
What do you foresee as the main challenge in the first 12 months? 
Humans are by nature competitive and oncologists and scientists are human, all too human! So, I see the greatest challenge will be to continue to bring all of the experts in the ECMCs to come together so as to work collaboratively and co-operatively to realise these ambitions. I hope that that together with the ECMC programme office we can mobilise the enormous potential of the ECMC network so as to truly impact on the lives of people with cancer. Some of these areas I’ve mentioned here are part of systematic bold challenges and require every individual to focus their minds and efforts, but the ECMC network does have the potential to begin to tackle these challenges if we pull together as a collaborative and co-operative network. 
The next 12 months of what will be intense discussion and collaborative working with all the stakeholders will be critical in discerning whether this 2023-2028 ECMC quinquennium can go some way to realising its aims of accelerating innovative translational research, of realising globally competitive research delivery and of increasing patient centred and accessible research.
Gary will be meeting with ECMC Leads over the next few weeks/months, if you have any feedback do send it through to and we can pass it on.