Lycera has started a Phase 1b clinical trial to assess the safety of a combination of its immunotherapy LYC-55716 and Merck’s Keytruda (pembrolizumab) as a lung cancer therapy.
The trial will involve patients whose non-small cell lung cancer, or NSCLC, has spread to other parts of their body.
LYC-55716 reprograms the immune system to fight solid tumors better.
It is an agonist, or substance that binds with a receptor to trigger a response. Its full scientific name is selective retinoic acid-related orphan receptor-gamma agonist — or RORgamma agonist for short.
RORgramma is a protein that acts as an immune cell master control switch. A RORgamma agonist reprograms immune cells to give them more punch against cancer. It also dampens their immunosuppressive mechanisms.
Essentially, LYC-55716 lifts the brakes on immune function and steps on the accelerator.
The tumors of mice treated with it grew slower, and the animals lived longer, Lycera said.
Keytruda works by blocking a pathway that cancer cells use to evade immune system detection. That pathway is the PD-1 protein, which is found on the surface of many cancer cells.
When Keytruda blocks the pathway, immune T-cells are able to find and destroy cancer cells again.
“The oncology [cancer treatment] community is very interested in finding novel immunotherapy approaches that can stand alone or complement the activity of PD-1” inhibitors, Dr. Ross Camidge, the trial investigator, said in a press release.
“PD-1 inhibition has completely changed oncology, but use of these agents alone appears to have convincing activity only in a minority of patients,” he said. “Many different combinations of specific novel immunotherapies are being tried, but the challenge has been selecting which combination is right for which patient.
“In theory, the very broad immune reprogramming potential of RORgamma agonists is, therefore, very attractive to explore for synergy with PD-1 inhibition. I am very pleased to be involved with this research initiative and look forward to assessing this agent [LYC-55716] in this novel combination.”
About 18 patients whose lung cancer progressed after previous treatment are expected to take part in the trial. In addition to assessing the LYC-55716-Keytruda combo’s safety, the trial will look at patients’ ability to tolerate the treatment.
Another trial objective will be to see how patients respond to the combination.
Researchers will also study the combo’s effect on levels of immune system biomarkers in tumor tissue and blood. They will do this by comparing the levels in tissue and blood samples they collect before and after treatment.
Meanwhile, Lycera is evaluating LYC-55716’s effectiveness as a stand-alone cancer treatment in the Phase 2a portion of a Phase 1/2a trial (NCT02929862). Researchers are continuing to enroll patients with six kinds of advanced cancer in the study, including NSCLC.
“We are thrilled with the progress of our cancer immunotherapy program, which is now advancing in two proof-of-concept clinical studies of LYC-55716 in monotherapy [as a stand-alone treatment] and combination treatment,” said Paul Sekhri, Lycera’s president and chief executive officer. He said the company expects “to report interim findings from ARGON by the second half of this year, and early safety and efficacy data from the Phase 1b combination study in the middle of 2019.”
