Accelerating the Pace of Discovery…From Laboratory to Bedside

By Kerri Kaplan

As the world’s primary catalyst for pancreatic cancer research, the Lustgarten Foundation funds critical research projects where creative risks yield high rewards. Lustgarten is driving forward basic science that is being translated into potentially life-saving treatment options via the Robert F. Vizza Lustgarten Clinical Accelerator Initiative. Drs. Tyler Jacks and Brian Wolpin, leaders of the Lustgarten Lab at MIT and the Lustgarten Lab at Dana-Farber, respectively, shared their experiences moving discoveries from the laboratory bench to the patient’s bedside as part of our LustgartenLIVE! webinar series: From the Lab to You: Clinical Advances.

Clinical trials are essential to accelerating progress in developing new therapies for patients at all stages of the disease. Every new medicine and treatment began with volunteers participating in clinical trials, not only as a way to potentially help themselves, but to advance the understanding of medications for future patients.

Clinical Trials: Making New Treatments Possible

A clinical trial is a carefully planned study to determine if a specific treatment is safe and effective in humans and discover how it compares to the standard of care. Each trial is focused on finding a better way to understand, prevent, diagnose, or treat a disease. Outside experts scrutinize all clinical trials to prioritize the health and safety of the patient. Before a clinical trial can even begin, it must be approved through a rigorous scientific, medical and ethical process at the federal level and at the institution where a patient receives treatment. While the trial is ongoing, regulatory and governmental bodies monitor the trial to ensure patient safety, and a trial can be stopped any time there are safety concerns.

Clinical Trials May Provide the Best Treatment Option for Pancreatic Cancer Patients

Clinical trials provide an opportunity for participants to:

• Play an active role in their own health care
• Gain access to new research treatments before they are widely available
• Increase the options for treatment when standard therapy has failed
• Obtain expert medical care at leading health care facilities during the trial
• Help others by contributing to the advancement of medical knowledge

Robert F. Vizza Lustgarten Clinical Accelerator Initiative (CAI)

The Lustgarten Foundation offers patients and their families newfound hope through the Robert F. Vizza Lustgarten Clinical Accelerator Initiative (CAI). Clinical networks are being built to be more efficient because the best science, clinical trial expertise, biomarker expertise, and access to patients rarely exist at one institution. Each clinical trial is small and heavily aimed at understanding treatment sensitivity and resistance in pancreatic cancer.

Typical CAI studies feature an in-depth analysis of a relatively small number of patients. These smarter clinical trials generate large volumes of clinical and mechanistic data, which can help to reveal not only if a treatment is safe and effective but show how to improve treatments either by changing the treatment regimen or refining the patient population targeted. Data from CAI studies will be stored in a Lustgarten clinical data platform accessible to scientists now and in the future.

The Future Holds Hope!

Cancer researchers won the Nobel Prize in medicine in 2018 for the discovery of the checkpoint blockade, which revolutionized cancer therapy for some cancers. The body’s immune system contains T-cells that can recognize and destroy cells expressing cancerous proteins. Most tumors create a highly immunosuppressive environment that disables these T-cells and protects the tumor. Checkpoint inhibitors remove the brakes on the T-cells to attack cancer more aggressively and destroy tumors.

Checkpoint inhibitors have been very effective in treating melanoma and lung cancer. However, they have not worked well in pancreatic cancer, where many other mechanisms keep the immune system from destroying the tumors. Researchers have been looking for ways to disrupt these other mechanisms and make checkpoint inhibitors more effective in pancreatic cancer. Lustgarten-funded Distinguished Scholar, Dr. Douglas Fearon, demonstrated that a compound called plerixafor, originally developed to fight HIV, also will inhibit a pancreatic cancer pathway allowing immune cells to invade tumors in mice, enabling their destruction with checkpoint inhibitors.

Recapitulating work done in the mouse models, a phase 2 trial of plerixafor and the checkpoint inhibitor cemiplimab in metastatic pancreatic cancer opened in 2020 at Johns Hopkins. This trial may be the pivotal step toward finally opening the door to more promising immunotherapy treatment options for more patients.

This trial is supported under the Pancreatic Cancer Collective by the Stephen and Nancy Grand Philanthropic Fund.

Targeting Another Pathway Contributing to Blocking Immune Response Shows Remarkable Results

“Sometimes the immune system wins the battle and eliminates cancer before it even develops,” shared Dr. Tyler Jacks, referencing an immunotherapy strategy destroying pancreatic tumors in mice developed by his team at the Lustgarten Lab at MIT. The new therapy combines three drugs that help boost the body’s immune defenses against tumors.

The MIT team discovered a less familiar pathway, called TIGIT, provided a promising new target for cancer immunotherapy. When they combined a molecule that inhibits the TIGIT pathway with a molecule known to stimulate an immune response and an immune checkpoint inhibitor, they found pancreatic tumors shrank in about half of the mice given this treatment. Miraculously, in 25% of the mice, the tumors disappeared completely. Most importantly, the tumors did not regrow after the treatment was stopped. The mice were cured.

This triple combination will now be tested on humans at Dana-Farber as part of the CAI. The MIT team will continue to analyze which types of pancreatic tumors might respond best to this drug combination and continue further animal studies to see if they can boost the treatment’s effectiveness beyond the 50% they observed in this study.

The Synergistic Effect of Bringing Together Leading Scientists From Multiple Institutions

Dr. Wolpin credits the abundance of new trials to the Lustgarten Foundation’s past research efforts, creating opportunities in the clinic. In one specific example, Dr. Wolpin’s team at the Lustgarten Lab at Dana Farber connected with another Lustgarten-funded researcher about opening a new and improved trial to one that previously failed.

“When you are funded by the Lustgarten Foundation, you meet others funded by the Foundation, and ideas present themselves that are new and innovative,” said Dr. Wolpin.

The Dana-Farber team sought to understand why the trial did not work when they heard about similar work at the University of North Carolina. This led to a collaboration combining the drug studied at Dana Farber with the drug studied at UNC, and this research is now taking place at both sites.

Research is Fundamental

The Lustgarten Foundation funds the world’s preeminent pancreatic cancer researchers, driving the pursuit of bold and innovative science toward earlier detection and better treatments and transforming pancreatic cancer into a curable disease. Our mission is rooted in the belief that research is fundamental, in fact, it is the only way to produce real results. Our groundbreaking new research program—the Robert F. Vizza Lustgarten Clinical Accelerator Initiative—is ensuring the most pioneering research advancements in clinical trials and new treatments are possible, so patients have many more tomorrows with their families.

Learn more about clinical trials and discuss with your doctor trials that might benefit you.

LustgartenLIVE! webinar is made possible by the support of Ipsen and Elevation Oncology

Thank you to the following donors for supporting the Foundation’s Clinical Accelerator Initiative:
Eleanor Schwartz Charitable Foundation
Joseph Arena and Dr. Thomas D’Eletto Charitable Fund
Irving Hansen Foundation