immunotherapy clinical trial for liver cancer that, if successful, eventually could transform treatment of the usually fatal disease into an outpatient procedure.
Patients with advanced hepatocellular carcinoma, the most predominant type of liver cancer, have a very poor prognosis and limited treatment options. The rate of liver cancer diagnosis has more than tripled since 1980, according to the American Cancer Society. About 42,030 new cases are predicted and about 31,780 people are expected to die from the disease in 2019.
To improve survival rates for liver cancer, City of Hope physician-scientists have started a phase 1/2 research clinical trial that engineers a person’s own immune T cells to target an alpha fetoprotein (AFP)-peptide/HLA-A2 complex — a small protein/antigen highly expressed in hepatocellular carcinoma. It is secreted from liver tumor cells and is somewhat specific to that organ.
“The novel T cell platform has the potential to transform T cell therapy into an outpatient procedure,” said Yuman Fong, M.D., director of the Center for Surgical Innovation at City of Hope, co-investigator of the ongoing clinical trial and The Sangiacomo Family Chair in Surgical Oncology. “We, Eureka Therapeutics and others are designing T cell therapies with low toxicity.”
A True Targeted Approach
City of Hope is the first of five institutions in the United States to test Eureka Therapeutic’s experimental ET140202 ARTEMIS™ T cell therapy on patients who are AFP-positive and HLA-A2 positive. The goal is to create a true targeted approach to using immune cells to home in on only tumors, and nothing else.
The patients who are selected for the clinical trial have metastatic or locally advanced, inoperable liver cancer and have failed or not tolerated at least one line of treatment for advanced hepatocellular carcinoma. The clinical trial tests for safety and tolerability of ET140202 T cells. If the initial study participants react favorably, the trial will move into drug-efficacy testing. The study aims to assess patients for two years and to follow them for 15 years post-treatment.
“Traditional immunotherapy such as checkpoint inhibitors releases the brakes on the immune system, which allows it to sometimes attack the tumor but can also lead to attacks on other parts of the human body,” said Daneng Li, M.D., principal investigator of the ongoing study and a medical oncologist at City of Hope.
This approach engineers immune cells to directly attack a protein that is expressed on liver cancer. We are trying to individualize treatment for patients with advanced liver cancer.”
ET140202 T cell therapy was first tested in China in a first-in-human, proof-of-concept study. The ongoing study has demonstrated a favorable safety profile with no cytokine release syndrome (a serious side effect that includes overexpression of certain proteins) or drug-related neurotoxicity.
The engineered ET140202 T cells recognize and bind to the AFP peptide/HLA-A2 complex, become activated and kill the liver tumor cells.
Extending the reach of CAR T
“This clinical trial grew out of a laboratory collaboration with Eureka Therapeutics and is another example of City of Hope’s goal to extend immune-based T cell and CAR T cell therapy to people across the spectrum of human cancers,” said Stephen Forman , M.D., director of the T Cell Therapeutics Research Laboratory at City of Hope, co-investigator of the clinical trial and the Francis & Kathleen McNamara Distinguished Chair in Hematology and Hematopoietic Cell Transplantation.
The ongoing clinical trial further advances City of Hope’s portfolio of experimental treatments for advanced liver cancer. Now, City of Hope patients with liver cancer may not have to resort to standard treatments for their advanced disease until their fourth line of therapy. In total, City of Hope has 20 ongoing T cell and CAR T clinical trials.
Cheng Liu, Ph.D., founder and chief executive officer of Eureka Therapeutics, a clinical stage biopharmaceutical company developing novel T cell therapies that harness the power of the immune system, said, “We are pleased to work with City of Hope to bring ET140202 therapy to patients with advanced hepatocellular carcinoma. Our approach has been to use our ARTEMIS™ T cell platform with higher target specificity to address the safety and other challenges in the treatment of solid tumors. Hepatocellular carcinoma is a devastating disease, and we are delighted that City of Hope is using their broad expertise to potentially accelerate our efforts and provide additional opportunities to combat this and other diseases.”