NEW YORK – LUNGevity and the Moffitt Cancer Center are making a push to better quantify and improve biomarker testing access for Black patients with non-small cell lung cancer.
Within the Joining Us Together to Improve Lung Cancer Equity (JUSTICE) initiative, researchers are conducting a 260-patient study, within which individuals with NSCLC who identify as Black or African American will receive Merck's immunotherapy Keytruda (pembrolizumab) at 19 or so community treatment sites. Within this study, the patient advocacy and research organization LUNGevity, together with Moffitt, hopes to home in on biomarkers of response to Keytruda specifically among Black NSCLC patients. The study is funded by cancer genomic profiling company Foundation Medicine and Merck.
According to Upal Basu Roy, the executive director of research at the LUNGevity Foundation, looking uniquely at this patient population is crucial given that historically most immunotherapy trials, including those that led to regulatory approvals, have had woeful underrepresentation when it comes to Black and African American patients.
"From a clinical trial perspective, if you look at all the immunotherapy clinical trials in the US that led to approvals of these drugs for advanced stage lung cancer, only about 3 percent of the total population was African American," Basu Roy said. "That leads to a very pressing question: How does immunotherapy behave in the African American population?"
According to Basu Roy, Moffitt and LUNGevity initially launched the trial seeking to better understand how Black patients with advanced NSCLC respond to Keytruda. Patients in the trial will undergo circulating tumor DNA testing throughout their treatment to help researchers home in on blood-based markers associated with Keytruda response. But within this study, researchers are also trying to find solutions to a far more intractable problem in precision oncology: the lack of biomarker test access for Black patients.
Given how many biomarker-directed targeted drugs and immunotherapies there are for NSCLC, biomarker testing and treatment should go hand in hand in this setting for all patients. For example, according to Keytruda's label, patients should undergo PD-L1 expression testing to determine if they are eligible for single-agent therapy. Additionally, patients should also undergo biomarker testing to see if they have mutations in EGFR, ALK, or ROS1, and therefore, receive targeted therapy.
"Immunotherapy is often a treatment of exclusion," Basu Roy said. "You need to get tested to receive immunotherapy, so there's a precision medicine aspect of that." Access to biomarker testing, however, has historically been so low among Black patients that these patients miss out on these precision treatments. This is where Moffitt and LUNGevity's ambitions to better understand biomarker testing barriers for Black patients come into play. Nested within the larger study to understand Keytruda's efficacy in Black NSCLC patients, LUNGevity and Moffitt have launched an effort, dubbed the Community Outreach to Empower Black Patients with Non-Small Cell Lung Cancer (COMPASS), in which they are systematically trying to quantify testing barriers and identify actionable solutions. This effort is backed by a $200,000 Foundation Medicine grant announced last month, which will be split evenly between LUNGevity and the Moffitt Cancer Center.
"We are not trying to quantify rates of disparities and levels of disparities," Basu Roy said. "That's already been quantified." Instead, LUNGevity and Moffitt want to quantify what they're calling "patient activation," a measure of patients' knowledge, skills, and confidence about managing their healthcare.
"The patient activation guideline is a very precise quantitative construct that lets us measure how empowered patients feel about making decisions about their healthcare at a given point in time," he said. The COMPASS study will use this scale to longitudinally measure "patient activation" at the point of diagnosis, and then again after they've received two to three cycles of immunotherapy within the trial.
Patients will anonymously complete surveys, which include both multiple choice and open-ended questions, to not only track their levels of activation but also gauge their knowledge and awareness of biomarker testing and clinical trials; understand the barriers they face in participating in research; and learn about the changes they'd like to see within the medical community to improve access.
"The most important part will be learning from the patient community about what actions we as the healthcare ecosystem can take to reduce some of those barriers to awareness about biomarker testing," Basu Roy said. "We see COMPASS as a great opportunity, as this is an enriched population obviously, to really learn from the African American community." The goal in administering the surveys several times throughout the study, he added, is to evaluate if patients' awareness and activation changes during the course of the study.
The researchers are also querying patients' providers, most of whom will be community oncologists, about the barriers they have experienced in trying to access biomarker testing and why they may not be providing precision medicine to Black patients specifically, Basu Roy said.
"This study is not a general sweep of barriers to precision medicine in clinical trials; it is very focused on this community," he said. Providers will answer questions about whether they offer special programs to members of the Black community and whether they offer financial support or extra education surrounding clinical trials and biomarker testing.
A key component of these surveys, Basu Roy added, involves asking patients about their perceptions of racism when it comes to their healthcare teams. "That's an incredibly critical part of this project," he said. "It's vital to understand this issue as holistically as possible."
LUNGevity and Moffitt are now waiting for final IRB protocol approval, after which they can begin actively enrolling patients. One major caveat to the COMPASS trial, which Basu Roy recognized as an ironic limitation, is that in recruiting patients to a study designed to understand barriers to participating in studies, COMPASS researchers will themselves need to grapple with these very barriers.
It may be that the community sites that participate in COMPASS will be those that already have established outreach programs in place and can recruit minority patient communities, Basu Roy said. Does this inherently skew the study population away from the neediest communities? He can't say for sure, but he's hoping that the learnings from COMPASS will ultimately help reach those patients who have never had the opportunity to participate in a study like this.
The true gold standard for identifying barriers to participating in clinical trials, Basu Roy noted, would be a randomized-controlled study, in which one arm includes patients from the Black community who did enroll in a trial and a control arm includes patients who never enrolled in a trial or don't have access to one at all. But of course, that's impossible to accomplish, he said, since the minute those patients are recruited onto a control arm of that theoretical trial, they become part of a trial.
"We know that the barriers will be impediments to accruing patients [on COMPASS]," he said. "We've spent a lot of time trying to figure that out. It's a tricky problem, and we're trying to piece together this entire puzzle."
Despite these ironies challenging patient recruitment, in Basu Roy's view, the research community still has a moral imperative to better understand and address race-based disparities in accessing precision cancer medicine.