April 4, 2014 - Developing new treatments for diseases like cancer is always a race against time. We must get effective and safe medicines to patients as quickly as possible.
Rooted in a deep understanding of tumor biology, we are now developing smarter cancer-fighting strategies. And as a result, we’re beginning to see signals of efficacy earlier than ever before – as early as Phase I clinical trials. We can now rapidly identify which investigational medicines have the strongest potential to help people with cancer because we’re reimagining how we approach Phase I in the first place.
Let the science move the medicine
Phase I clinical trials are the melting pot of basic science and clinical medicine. Entering Phase I with strong scientific hypotheses and smart trial designs is the key to moving a medicine forward as quickly as possible.
As we learn earlier which medicines do or do not have the potential to help patients, we must adapt the path forward based on those results. For instance, advances in molecular biomarkers and diagnostics allow us to “personalize” trials, identifying patient sub-groups who are most likely to respond to treatment. When an investigational medicine shows promising efficacy in a biomarker-guided Phase I study, we may skip Phase II studies entirely, and move into the definitive test in Phase III.
Today, all of Genentech’s investigational cancer medicines entering Phase I have a biomarker strategy component to their development.
In addition, some of our other investigational medicines are designed to have potential for broader populations. In this case the best strategy may be to first conduct a trial across a number of cancer types. Once an efficacy signal is identified, Phase I extension studies could further evaluate the investigational medicine in tumor types that seem to be responding well. For example, we recently conducted large Phase I studies in hundreds of patients in more than five different tumor types from which we were able to identify select tumor types to further evaluate.
It’s critical that we take advantage of opportunities to shorten the lengthy process of drug development when the science supports it.
We’re even seeing a shift in the way regulatory authorities think about the role of Phase I data in the path to approval, as my colleague Michelle Rohrer discusses here. This can have a huge impact on patients’ lives, and it’s changing the way we are looking at developing new medicines.
Go back to the start
These are major changes. As a result, we may need to fundamentally rethink what a Phase I trial is at its core.
Are there combination therapies we can take advantage of from Day 1? Does our understanding of the tumor biology give us clues about whether we should be hitting two or more targets at once rather than testing them separately first?
Can we obtain biopsies on progression and then add a second drug to target a resistance pathway?
Do we forego the traditional Phase I cancer efficacy endpoint of response rate (RR) or pharmacological measures in favor of overall survival or perhaps a potential surrogate endpoint like progression-free survival (PFS) or pathological complete response (PCR)?
Should the trial include people with any kind of solid tumor or blood cancer, or can we zero in on a single tumor type that’s most likely to benefit?
Can we go even further and only include patients selected based on specific biomarkers?
These decisions about how to change Phase I trials can’t be taken lightly. And the answers aren’t always clear. But this isn’t just about changing the way we conduct trials –it’s about elevating treatment options for people with cancer, as quickly as possible. And that’s always worth the effort.
Stuart Lutzker is the Vice President of Oncology Exploratory Clinical Development and oversees the early clinical development of Genentech's oncology pipeline molecules. He joined Genentech in 2004 as an assistant medical director and assumed leadership of the Oncology Exploratory Clinical Development Group in 2008. He has represented Genentech on a number of outside panels evaluating oncology drug development and is a member of the NCI Clinical Trial Design Task Force.
Stuart earned his BA (Summa Cum Laude) in Chemistry from Columbia University and an MD-PhD degree in Biochemistry from Columbia University College of Physicians and Surgeons. He completed his internal medicine and medical oncology training at Yale and then pursued a research fellowship in the Department of Molecular Biology at Princeton University. He then joined Robert Wood Johnson Medical School with a dual appointment in Internal Medicine and Biochemistry and co-directed the Lung Cancer Clinic at the Cancer Institute of New Jersey (a NCI Comprehensive Cancer Center). Stuart is the recipient of numerous awards including an ASCO Young Investigator Award and was previously named a V Foundation Scholar and Pfizer New Faculty Scholar.