The oncology field has come a long way in the last 15 years, with the identification of novel targets, continued advancements in immuno-oncology and cell therapy, and the discovery of new ways to inhibit oncogenic proteins once thought of as un-druggable. As sponsors transition from preclinical to clinical development, they face numerous challenges—understanding the competition and evolving standard of care, designing effective protocols, navigating the regulatory landscape, identifying investigators and sites, recruiting and retaining patients, and collecting and analyzing data.
It is important for sponsors to work with partners who can leverage firsthand experience to develop strategies for addressing not only these known obstacles, but also unexpected hurdles that arise throughout the clinical trial journey.
Evolution of the cancer treatment landscape
Oncology therapies are often categorized into five pillars (see Figure 1). For thousands of years, surgery was the primary pillar, and it remains a foundational treatment for oncology patients. In the late 1800s, radiotherapy—which uses high-energy particles to destroy cancer cells—was established. Current estimates show that approximately half of patients with cancer receive some form of radiotherapy. Cytotoxic chemotherapy followed in the 1940s when, following World War II, a derivative of mustard gas was used to treat patients with lymphomas. Shortly thereafter, Sidney Farber used a compound related to folic acid to drive remissions in children with acute lymphocytic leukemia (ALL). In the years that followed, long-term remissions and cures of patients with Hodgkin’s lymphoma (HL) and testicular cancer were observed.
As basic research yielded insights into oncogenic drivers, molecularly targeted therapy became the fourth pillar of cancer treatment. Most of these therapies—including treatments targeting CD20, HER2, BCR-Abl, EGFR, RAS, ALK, ROS, NRTK, MET, and RET—are commonly used today as standards of care. Directly targeting drivers of cancer has generally led to greater efficacy and fewer side effects than cytotoxic chemotherapy.
Finally, immunotherapy is coming of age as the fifth pillar. The history of immunotherapy dates to over 100 years ago when William Coley, a surgeon at Memorial Hospital, developed a treatment using heat-killed bacteria to stimulate a patient’s immune system against cancer. Today, there is a wide and growing variety of immunotherapies, ranging from IL-2 and checkpoint inhibitors to bispecific T- and NK-cell engagers, oncolytic viruses, cancer vaccines, and different types of genetically modified cell therapies.
Current oncology clinical trial environment
The regulatory and commercial success of checkpoint inhibitors has fueled tremendous growth in the field, as demonstrated by the 1,430 open US trials involving these immunotherapies.2 Many of these studies involve follow-on therapies hitting the same targets as approved treatments with similar mechanisms of action (see Table 1).
| Target | Number of Therapies | Open/Planned Trials |
|---|---|---|
| PD-(L)1 | 88 | >3,000 |
| CD3 (bispecific) | 53 | 160 |
| EGFR | 48 | 540 |
| HER2 | 47 | 231 |
| CD19 | 37 | 161 |
| BCMA | 28 | 124 |
Table 1. Top oncology therapeutic targets for US corporations with oncology therapies with Phase I approval2
Competition is intense across validated targets and while this approach reduces technical risk, it involves significant commercial risk. The crowded research environment in single targets—coupled with a downturn in investments and mergers and acquisitions (M&A)—increases regulatory scrutiny and puts even more pressure on sponsors to make informed, rational decisions on what to bring forward in their pipelines and how to efficiently execute their clinical trials.
Driving execution of oncology clinical trials
Recognizing known obstacles to trial execution and putting plans in place to address them is critical for increasing study efficiency. As competition increases, there is a clear and present challenge in finding sites and patients that are willing to participate in clinical trials. According to a recent analysis of a national sample of data from 1,200 institutions, the estimated participation rate in cancer treatment trials was
6.3%. Not surprisingly, enrollment was highest at National Cancer Institute (NCI)-designated comprehensive cancer centers, with a nearly 19% participation rate. A comparatively large number of oncology patients in the US are treated at community cancer programs, but the participation rate is only 4.4%, suggesting that there is an opportunity to use novel data sources and innovative technology to strategically identify the right patients and sites for clinical trial enrollment.
Too often, we have seen community sites selected for clinical trials based on investigator interest and historically short activation timelines. Site selection—especially at the community level—requires close attention to detail across the following five dimensions:
- Patient population. Does the site have access to the patient population under investigation? What is the proximity of those patients to the site? Are there other trials at the site that would compete for the same pool of patients?
- Site staff experience and resources. Does the staff have the necessary availability, credentials, and experience with regulatory, contracts, budgeting, and protocol-specific requirements and procedures? Does the site have adequate space and storage, as well as the essential equipment?
- Historic performance. How has the site performed in the past with respect to enrollment? Quality? Site activation? Data entry?
- Trial experience. Does the site have experience with the indication? The treatment modality? What about benchmark trials?
- Screening and enrollment. Does the site utilize specific strategies and tools to support these key study activities?
Incorporating innovative approaches to identifying patients at active sites
At Precision for Medicine, we are exploring new data-driven strategies for identifying experienced investigators and sites that can help promote clinical trial awareness, access, and participation, including among underrepresented patient populations. By incorporating claims data and social determinants of health (SDOH) from over 350 million patients—representing 98% of payers and over 1.8 million healthcare providers—into a validated process, we help researchers and sponsors develop lists of potential sites. After qualifying those investigators and sites, we build site- and protocol-specific patient lists within our proprietary EHRConnect™ technology. EHRConnect offers the same core functionality as other electronic health records, with the added capability of generating high probability lists of eligible patients that meet defined clinical and demographic criteria, maximizing enrollment and diversity.
Conclusion
In a clinical trial landscape where competition is high and access to capital is difficult, sponsors need to incorporate pragmatic use of tools that help them overcome known obstacles. Qualified sites and eligible, willing participants are critical to the success of any oncology trial. Leveraging technologies that transform real world data—from claims and SDOH to clinical and molecular information—into insights that support identification of patients at active trial sites and engagement with community oncology networks not only optimizes awareness and recruitment, but also enhances access and much-needed diversity.
