Car T Cell Therapy Being Tested in Pancreatic Cancer

March 23, 2017
Beth Fand Incollingo

CURE, GI-Special-Issue, Volume 1, Issue 1

Experimental treatment uses engineered T cells to target prostate stem cell antigen.

A FLEDGLING BUT PROMISING form of immunotherapy known as CAR T cell therapy has been adapted to hit a new biologic target in the hopes that it will effectively fight advanced pancreatic cancer. The technique is being tested in a phase 1 trial designed to enroll up to 30 patients with the disease.

In CAR (chimeric antigen receptor) T cell therapy, immune cells, also known as T cells, are removed from a patient’s body and engineered in a lab to recognize a specific biologic marker that drives a cancer, and to destroy cells that carry it; these special T cells are then returned to the patient to multiply and do that work. The therapy being tested in this trial, BPX-601, targets prostate cancer stem cell antigen.

Despite its name, the prostate stem cell antigen (PSCA), a protein-coding gene, is naturally produced by the bodies of both men and women, and it does, indeed, have a relationship to pancreatic cancer. “It is a protein found on the surfaces of cells that was initially identified as a tumor antigen in prostate cancer, but subsequent investigations have revealed an upregulation in other cancers, including pancreatic cancer,” said the trial’s principal investigator, Carlos Becerra, M.D., of Baylor Health Care System, in Dallas. In fact, he said, 60 to 80 percent of pancreatic cancers express PSCA. “Studies have shown it to be effective in treating human pancreas cancer tumors in mice.” Those studies were conducted by Bellicum Pharmaceuticals, Inc., the developer of the CAR T- cell therapy that targets PSCA and the sponsor of the new trial.

Trial Details

The trial (NCT02744287) is being conducted solely at Dallas’ Baylor Sammons Cancer Center, through the Baylor Scott & White Research Institute. It is testing BPX-601 in humans for the first time. Other CAR T cell therapies have already been tested in humans in early-phase trials for a variety of cancer types, but no such therapy has yet been approved by the U.S. Food and Drug Administration.

Four patients have been enrolled in the trial of BPX-601, and recruitment is continuing. Participants must be adults with nonresectable pancreatic adenocarcinoma, and their tumors must test positive for expression of PSCA. Patients may have experienced disease progression after surgery or while taking chemotherapy or an investigational therapy, or they may have refused standard treatments. They must have adequate organ function and a life expectancy of more than 12 weeks; as part of the trial, they will be followed for up to two years.

Autologous T cells will be collected from the patients via blood withdrawal and genetically modified using a retrovirus to express the anti-PSCA chimeric antigen receptor. Then, the T cells will be reinfused into each patient according to a dose-finding schedule, assuming the recipient has a T cell count that’s low enough to allow the engineered cells to multiply and work. The aim of the trial is to test BPX-601 for feasibility, safety and dosing. The trial will also evaluate the safety of rimiducid, a drug that will be infused after BPX-601 is administered; investigators will consider how long the engineered CAR T cells remain at work following a single rimiducid infusion.

Rimiducid, developed by Bellicum, is designed to trigger T cell activation and proliferation in patients administered BPX-601. It helps enable control over the activity and potency of the therapy.

“It is the activation switch and has dual functions,” Becerra said. “Once administered, it dimerizes, or couples the proteins together, to create a cluster that triggers the signaling cascade. Rimiducid also increases the activation of the T cell, expanding its number and allowing it to survive longer.”

The side effects of rimiducid are similar to those of placebo, and are to be determined for BPX-601, although they may be similar to those of CAR T cell therapies, Becerra said. The most dangerous of those is cytokine release syndrome, which can cause fever, nausea, chills, low blood pressure, headache and rash.

Trial Could Open Doors

Becerra said he’s hopeful about the trial because there’s a great need for new methods of treating pancreatic cancer. When looking at all stages of the disease combined, patients have a one-year relative survival rate of 20 percent and a five-year relative survival rate of 7 percent.

Standard treatment includes combinations of surgery, chemotherapy and/or radiation, depending on cancer stage. “It’s important because we constantly strive to find ways to improve survival for our patients,” he said. “The Baylor Scott & White Research Institute’s mission is to support research that brings innovative treatments to the bedside. This trial is one of several strategies we are using to attack one of the deadliest forms of cancer. It helps open the door for new ways of treating pancreatic cancer using a person’s own immune system.”

He added a note of restraint, however.

“We are cautiously optimistic about this trial moving forward,” Becerra said. “Although we believe this treatment holds great promise, it is only the beginning of the clinical trial process, and only through the completion of these trials will we know if it’s effective.”

Those interested in learning whether they might be eligible for the trial can find a complete list of eligibility and exclusion requirements at clinicaltrials.gov. Alternatively, prospective enrollees can contact patient navigators at the Sammons Cancer Center at (214) 820-3535.