It bears repeating: Clinical trials are essential to the development of new treatments.
These trials also find the most effective ways to detect and diagnose disease. And even when a trial “fails,” important information is gained about the disease itself, information that cannot be gained in the laboratory. But let’s be honest; clinical trials are a huge undertaking. Years may pass while a trial moves from the lab into various clinical phases. And for aggressive, tough-to-treat diseases like pancreatic cancer, time is of the essence.
Time is the overarching theme of the Robert F. Vizza Lustgarten Clinical Accelerator Initiative. Vizza led the Lustgarten Foundation as its first President and CEO and, later, as Chairman of the Board of Directors until his retirement in 2020. The Initiative focuses on launching new clinical studies in a way that not only shortens the time required to move from concept to study, but also to develop new trials so that as much data as possible is generated in that shorter time frame. Its goal, of course, is to improve the lives of pancreatic cancer patient outcomes.
“I have to say that I am really excited about this effort,” comments Elizabeth M. Jaffee, M.D., of Johns Hopkins, in Baltimore, Maryland, who serves as Lustgarten’s Chief Medical Advisor. Jaffee will lead the Initiative’s Translational Advisory Group (TAG), which is tasked with identifying both innovative concepts and potential therapeutic approaches and then accelerating their testing. The Advisory Group currently includes representatives from Dana-Farber Cancer Institute (Boston), Duke University (Durham, North Carolina), Johns Hopkins, Massachusetts General Hospital (Boston), Memorial Sloan Kettering Cancer Center (New York), Northwell Health (New Hyde Park, New York), NYU Langone (New York), Oregon Health & Science University (Portland), University of California San Diego, University of Pennsylvania (Philadelphia), and Yale University (New Haven, Connecticut).
“Lustgarten has a great track record, based on their past research efforts,” says Jaffee, who also serves as the Dana and Albert “Cubby” Broccoli Professor of Oncology at Johns Hopkins and Deputy Director, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins. “We have a lot of opportunities now to move things more quickly out of the lab and into the clinic with well-designed and very efficient clinical studies.”
Why Use Small Trials?
A core concept of the Clinical Accelerator Initiative is keeping the trials small—about 10-20 patients—at a network of sites that can execute the trials. “These trials will be and are being designed to inform our investigators very quickly whether patients are responding to treatment or not,” explains Jaffee.
“We can do that with these smaller trials. Each member of the Translational Advisory Group has an incredible amount of experience in designing and leading trials. The most important thing, though, is that the information we gather will ultimately improve our therapies that we test in clinical trials and eventually move to standard of care.”
The Accelerator in Action
In early 2021, Lustgarten awarded $5.1 million to fund three new clinical studies under the Clinical Accelerator Initiative. One of the studies will take place at Dana-Farber and builds on preclinical work conducted at the Lustgarten Foundation Pancreatic Cancer Research Laboratory at MIT. Cancer cells often use immune checkpoint proteins such as PD-L1 to suppress and evade an immune system attack, essentially blinding T cells, the body’s natural immune system defenders, to their presence. This is where a class of drugs called checkpoint inhibitors comes into play. In this preclinical study, the MIT researchers confirmed work from previous studies showing that PD-L1 is not highly expressed on pancreatic cancer cells. But they found that most pancreatic cancer cells express a protein called CD155, which activates a receptor on T cells known as TIGIT. When TIGIT is activated, the T cells enter a state known as “T cell exhaustion,” in which they are unable to mount an attack on pancreatic tumor cells.
The goal of the upcoming clinical trial at Dana-Farber will look to “reawaken” T cells that penetrate the pancreatic tumors but are rendered “exhausted” and ineffective by signals from the tumor. The clinical study will test a novel combination of drugs designed to simultaneously activate the T cells and block the inhibitory signals from the tumor.
Two studies at Johns Hopkins will build on work coming from Jaffee’s team exploring the use of vaccines in the treatment of pancreatic cancer. Both newly funded studies will look at novel combinations of vaccines and drugs targeting the immune system to determine if they can overcome pancreatic tumors’ resistance to immune therapies. The two studies build on clinical data generated in ongoing clinical trials at Johns Hopkins and will target specific immune barriers identified as part of those studies. One study will enroll metastatic patients, while the other will target patients who are eligible for surgery.
The vaccine was developed more than a decade ago in Jaffee’s laboratory and given to patients in trials by Johns Hopkins oncologist Daniel Laheru, M.D. Jaffee and Laheru are co-directors of the Skip Viragh Center for Pancreatic Cancer.
Since the vaccine was developed, Jaffee and her research colleagues are continuing to study cancer vaccines and vaccine combinations that overcome tumor-associated immune tolerance. “I think it’s fair to say that within the next few months we are going to get these studies off the ground,” Jaffee says. “And we are going to know quickly whether we are on the right track.” And that “knowing” is vital if the needle is going to move in the right direction for patients.
“It’s really no secret that we need better treatments for pancreatic cancer patients,” Jaffee observes. “But I think it’s so important to remember how far we’ve come in just a few years. We do have better chemotherapies, but we still need to improve on them. We have a better understanding of the biology of the disease, which will lead us to those better treatments. And we are certainly learning important information on the immune system’s role in pancreatic cancer.
“The patients need a win, and this Lustgarten Initiative is going to certainly help us get there.”