Precision oncology, with its vision of treating each patient with the exact right medicine, is within reach yet still remote. This paradox has forever hung over my career as an academic researcher, oncologist, and biopharmaceutical industry executive.
When I read the recent news about chimeric antigen receptor (CAR) T cell therapies targeting specific gene mutations in aggressive brain cancer, the vision seemed thrillingly close at hand. Patients with glioblastoma, a notoriously intractable, fatal malignancy, experienced “dramatic and rapid”—albeit short-lived—shrinkage of their tumors.1,2 The results are unprecedented in this setting.
But the vision seems far away when I remember that, despite advances in trial design and the vast volume of genomic data we have accumulated, precision oncology still cannot help most cancer patients.3,4 The heterogeneity of cancer, our still-limited understanding of its interaction with the immune system, and inequalities in access to testing and medicines remain persistent barriers to fulfilling the dream.5
One challenge at a time, we navigate multi-omics profiling, clinical trial design, companion diagnostics, regulatory strategy, and commercialization. And we do all this while staying focused on improving the patient journey, which is our North Star.
Exciting science must benefit patients and their families
When I was about eight years old, my brother died of spinal sarcoma. I remember his pain and my parents’ grief. That event made me keenly aware of the damage cancer inflicts on people’s lives.
As a professor in the Department of Medicine at the University of Calgary, I founded the Precision Oncology Experimental Therapeutics (POET) program to help advance precision oncology with biomarkers. However, I was frustrated that what I achieved in the lab did not directly benefit patients. There is a massive lag between momentous molecular discoveries and their usefulness to patients.
As a practicing oncologist, I was inspired by my patients' willingness to participate in clinical research and help advance the field. I had the privilege of treating Terry Morey, a lung cancer patient who has survived for 12 years since his diagnosis thanks to precision therapies for anaplastic lymphoma kinase (ALK)-positive lung cancer.6 Terry shares his journey in this report.
Ultimately, I found the best way to translate scientific innovations into therapies that help patients is to harness the biopharmaceutical industry’s powerful drive for a return on investment. I moved to industry from academia to be a part of that.
In my work with sponsors here at Parexel, I regularly confront a second paradox of precision oncology: we move closer to the tantalizing long-term vision only by solving practical short-term problems (some mundane, some near impossible). We navigate multi-omics profiling, clinical trial design, companion diagnostics, regulatory strategy, and commercialization one challenge at a time. And we do all this while staying focused on improving the patient journey, which is our North Star.
Precision oncology has been—and will continue to be—a slow unfurling. Patients are our guides and partners in this quest. They don’t have a say in which next-generation sequencing test or seamless study protocol is optimal, and they can’t make a drug commercially viable if it’s not. But without their willingness to contribute their time, energy, biological samples, and genetic data—and to enroll in clinical trials—the field won’t advance. A streamlined development program won’t matter if a product does not address what patients care about.
New developments in biomarker identification and innovative approaches to targeting them continue apace. The promise of AI assistance in unlocking molecular structures and the increasing use of readily modifiable nucleic acid sequences as therapeutics are two of the most promising avenues of advancing precision oncology. Our challenge is plotting a route through this volatile landscape.
Precision oncology has been—and will continue to be—a slow unfurling. Patients are our guides and partners in this quest.
Building a roadmap to the vision
The ideal precision oncology therapy will deliver maximum benefits with minimum off-target toxicities and be universally accessible. We have a long way to go.
This report examines some obstacles drug developers—academic researchers, small innovative biotech companies, and well-established pharma giants—encounter on the road to that ideal and how we help overcome them. I am proud to showcase the insights of Parexel’s talented, committed team of oncology-focused patient advocates, clinical and translational scientists, drug development experts, statisticians, data managers, and former regulators. I hope sponsors will find their experience helpful in bringing precision cancer medicines to market so that an ever-increasing proportion of cancer patients can benefit.
- Terry Morey is a charming 76-year-old Canadian lung cancer patient who has benefitted from participating in clinical trials of immunotherapy drugs. He provides an inspiring example of precision oncology’s power—in his case, the power of tyrosine kinase inhibitors—to change outcomes for patients and their families.
- Parexel’s Chief Patient Officer and a cancer survivor, Stacy Hurt, argues that democratizing access to genetic testing and the data it generates—plus enabling patients to find relevant clinical trials quickly— are critical to advancing precision oncology. We could achieve this with a few practical improvements to current care pathways.
- Angela Hirst and Karen McIntyre, Parexel site management experts, reveal five risk mitigation strategies for sponsors who want to conduct precision oncology studies at regional and community sites instead of relying on the usual major academic research centers. By bringing trials closer to patients, we give them access to cutting-edge treatments. Sponsors also benefit from faster enrollment times, more diverse patient populations, and the same high-quality trial data.
- We asked Parexel’s Global Head of Biomarkers & Genomic Medicine, Angela Qu, how advances in multi-omics data and computational analytics are accelerating the discovery and utilization of new biomarkers. After early exploratory biomarker research, companies often underestimate the effort required for the biomarker's technical, analytical, and clinical validation.
- Amy McKee, Sinan Sirac, and Pengfei Song are three former regulators who have collectively reviewed dozens of precision oncology applications. They offer three strategies for companies struggling to meet the FDA’s Project Optimus requirements. Extensive dose optimization requires sponsors to enroll more patients, gather more data, conduct more thorough analyses, and spend more time and resources on early-stage oncology trials.
- Parexel’s medical devices expert, Trisha Eustaquio, explains why sponsors must manage resources and take the least burdensome regulatory path to validate companion diagnostics (CDx). Making a seamless transition from research- to clinical-grade assays requires multiple strategic interactions with regulators.
- Winning regulatory approval without reimbursement is a Pyrrhic victory. In a roundtable with Wyatt Gotbetter, Parexel’s Worldwide Head of Access Consulting, I discuss how rapidly expanding testing capabilities have impacted access to personalized medicines and the role of large-scale datasets and real-world evidence in advancing the field.
The promise of AI assistance in unlocking molecular structures and the increasing use of readily modifiable nucleic acid sequences as therapeutics are two of the most promising avenues of advancing precision oncology.
Contributing Experts