While many lung and bladder cancer patients respond well to immunotherapy, they eventually succumb to the disease because the immune system can not detect the cancer cells. Two clinical trials will combine immunotherapy with epigenetic agents in order to allow the immune system to recognize and destroy the cancer cells.
Stand Up To Cancer (SU2C) announced on Thursday that nearly $5.5 million will be awarded to pursue clinical trials of epigenetic drugs to enhance tumor response to immunotherapy.
The grants, awarded to Van Andel Research Institute (VARI), will go towards 2 clinical trials that will test whether epigenetic and immunotherapy combination therapies can prolong survival in patients with lung and bladder cancer.
Bladder and lung cancer cause nearly 173,000 deaths in the United States every year. Both tend to respond favorably to immunotherapy. However, the immune system is sometimes not able to recognize or destroy the cancer cells because the cancer seizes epigenetic signals and makes itself undetectable.
“It is usually balanced by ‘on’ and ‘off’ signals that coordinate when to attack or retreat, but cancers can evade immune attack by commandeering the ‘off’ signal. We believe epigenetic modification will be able to reverse this and help bolster the body’s immune response,” said Stephen Baylin, MD, co-director of the Cancer Biology Division and associate director for research programs for Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Director’s Scholar at VARI, co-leader of the VARI-SU2C Epigenetics Dream Team, and co-leader of the lung cancer trial.
By combining drugs that connect the immune system with epigenetic agents, drugs that modulate gene regulatory systems, the trial will try to alter epigenetic signaling in tumor cells.
While both trials will combine the immunotherapy with epigenetic agents, they will address different issues. The bladder cancer trial will be focused on determining whether epigenetic drugs can reverse resistance to immunotherapy. This is an issue that an estimated 85% of patients endure. The trial will investigate whether guadecitabine can epigenetically reprogram tumors, reversing the resistance of bladder cancer to the immunotherapy drug atezolizumab.
The lung cancer trial will attempt to see whether epigenetic drugs can improve a patient’s response to immunotherapies across the board. It will combine the immunotherapy drug pembrolizumab with 2 epigenetic drugs, guadecitabine and mocetinostat.
“We have great hope that this approach will help the body’s natural immune response recognize and destroy cancer cells,” said Peter Jones, PhD, DSc, chief scientific officer of the VARI-SU2C Epigenetics Dream Team and co-principal investigator of the bladder cancer trial.
The bladder cancer grant is funded by Genentech and will afford the trial $2.9 million over 3 years. It is scheduled to open later this fall at the Fox Chase Cancer Center in Philadelphia, University of Southern California in Los Angeles, and Johns Hopkins University in Baltimore.
The lung cancer trial grant is funded by Merck and will provide $2.5 million over 3 years. It is expected to begin in the coming months and will be conducted at Memorial Sloan Kettering Cancer Center in New York, Fox Chase Cancer Center, and Johns Hopkins University Sidney Kimmel Comprehensive Cancer Center in Baltimore.