Making cancer history: an interview with Tim Yap

Sarah: You’ve had an extraordinary career – and it’s still very much ongoing. What first drew you to oncology and early-phase drug development?

Tim: Thank you, Sarah. Going back many years now, my first real exposure to oncology came during my senior house officer (SHO) rotation at the Churchill and John Radcliffe Hospitals in Oxford. I absolutely loved it. I was struck both by the deep, long-term relationships you build with patients and their caregivers, and by the scientific richness of the field – the biology, the pharmacology, the genomics. 

That combination of human connection and cutting-edge science really hooked me. I often cite the quote from Edward Livingston Trudeau, “To cure sometimes, to relieve often, to comfort always”, which I adapted to include “using scientific and clinical knowledge”.

After that rotation, I went on to a senior SHO role at the Royal Marsden Hospital, working with Martin Gore – an extraordinary mentor. His humour, charisma and deep humanity shaped so many of us. He taught me not just how to think about oncology, but how to be with patients and how to collaborate joyfully with colleagues.

At that time, Stan Kaye had just established the Drug Development Unit at the Royal Marsden and the Institute of Cancer Research (ICR) and I was immediately inspired by him, Johann de Bono and Ian Judson. I joined the unit for a year, conducting and designing early-phase trials, and then went on to do a lab PhD in molecular pharmacology at the ICR with Michelle Garrett and Paul Workman, working on the preclinical development of AKT inhibitors discovered at the ICR, one of which eventually led to capivasertib. We also investigated novel predictive and pharmacodynamic biomarkers in tumour and surrogate tissue, testing blood and eyebrow hair follicles. I didn’t have any eyebrow hairs for about six months – not so good for my social life!

Between my fellowship and PhD, I spent four and a half years entirely immersed in Phase 1 and lab drug development research. That time shaped my career and I remain deeply grateful to Cancer Research UK for funding my PhD. I feel a strong sense of giving back to the organisation that helped launch my career. 

I was subsequently appointed as a consultant medical oncologist and clinician-scientist at the Royal Marsden and the ICR, before moving to MD Anderson in 2016.

You’ve now worked extensively in both the UK and US systems. What do you think the two can learn from each other to accelerate innovation?

The health systems are, of course, very different, which affects everything – from access to standard therapies to how research is funded and conducted.

In the UK, funding is often more focused and coordinated, and remarkable discovery science comes out of that environment. The Experimental Cancer Medicine Centres (ECMC) network and the national infrastructure for research allow coordinated, efficient trials across the country. Researchers like Charlie Swanton have demonstrated beautifully what that can achieve.

In the US, the scale is different. There are more sources of funding and more opportunities to run very large or highly specialised molecularly driven trials. MD Anderson, where I have been working since 2016, can feel like a fire hydrant turned on full blast – there is so much happening. 

We’re also seeing rapid growth in China as a hub for early-phase trials. How do you see global collaboration shortening the path from discovery to patient benefit?

China has evolved extraordinarily quickly in the last few years. They start trials fast, they recruit efficiently, and costs can be significantly lower. But the future has to be global. At MD Anderson, for instance, we work closely with Chinese biotech companies as well as partners across Europe, Asia and the US. Global trials allow us to recruit diverse populations and understand important biological differences between ethnic groups. 

Another key issue is molecular testing. In the US, virtually every patient with metastatic disease receives next-generation sequencing as part of their standard-of-care cancer management. That model needs to expand globally. If we don’t know the molecular drivers of a patient’s tumour, we simply can’t match them rationally to the right therapies.

You are currently a member of the CDD's New Agents Committee and the chair of the DETERMINE Trial Steering Committee. From that vantage point, how can Cancer Research UK and the CDD best work with academia, biotech and pharma to accelerate new medicines?

Cancer Research UK and the CDD are uniquely positioned to act as conveners – to bring pharma, biotech, diagnostics and academic investigators together. We’re already seeing how Cancer Research UK’s umbrella platform trials like DETERMINE and the National Lung Matrix studies allow multiple companies and investigators to collaborate within a cohesive framework, matching molecular targets to rational therapeutics across tumour types.

Cancer Research UK’s reputation and national infrastructure make it an ideal organisation to unite stakeholders and support trials both operationally and financially. I fondly recall leading the the ComPAKT trial to investigate the combination of olaparib and capivasertib in molecularly selected patients. AstraZeneca provided the funding through the ECMC Combinations Alliance and we were able to very efficiently conduct this trial at multiple sites across the UK. There’s enormous potential for Cancer Research UK and the CDD to continue shaping the landscape of early-phase clinical and translational research in the UK.

You also sit on the Clinical Advisory Board for Cancer Research Horizons’ drug discovery division. Why is early clinical evaluation so critical?

Everything we do should have a clear line of sight to patient benefit. Drug discovery is expensive – financially and operationally. We simply can’t progress every programme. Early clinical insight helps prioritise which projects have potential and which should be stopped early. Making timely go/no-go decisions ensures that resources are focused on the most promising, clinically relevant compounds, reducing the risk of investing heavily in drugs that ultimately aren’t safe or effective.

Innovation in trial design is becoming increasingly important. What approaches do you think will have the greatest impact on efficiency?

We’re moving away from the classic Phase 1–2–3 trials model toward integrated early-phase programmes, followed by efficient late-phase registrational trials.

A major driver is the FDA’s Project Optimus initiative, which recommends formal dose optimisation before late-phase trials. That means not just identifying a maximum tolerated dose but understanding safety, tolerability, pharmacokinetics, pharmacodynamics, efficacy signals, and molecular responses.

While this makes early trials more complex, protracted and more expensive, in the long run it prevents costly post-approval dose or schedule changes. Importantly, this ensures that patients receive the safest and most effective dose and schedule of the drug from the start of late-phase registrational trials.

If a young doctor today wanted to pursue a career in drug development, what would you advise?

Do it if it is something you truly enjoy. It’s a long training path, and passion is essential. Having great mentors is also critical for lifelong guidance and support. I would seek clinical exposure to as many tumour types as possible, and if you can, spend time in dedicated Phase 1 trials units. It is a remarkably kind, close-knit and highly supportive community. I genuinely believe that early-phase clinical and translational drug development is the most exciting area in oncology, because we are at the forefront of making new drugs for patients and hopefully making cancer history.