Lycera announced the initiation of the Phase 2a portion of Phase 1/2a ARGON study of its novel immuno-oncology therapeutic candidate, LYC-55716 is a first-in-class oral, selective retinoic acid-related orphan receptor-gamma (RORgamma) agonist, designed to reprogram the immune system in patients with advanced, relapsed or refractory solid tumors. The Phase 2a is expected to enroll a total of approximately 75 patients with advanced cancer in six tumor cohorts (Non-Small Cell Lung Cancer (NSCLC), Squamous Cell Cancer of the Head and Neck (SCCHN), Ovarian Cancer, Gastric and Esophageal Cancer, Bladder Cancer, and Renal Cancer). These tumor types were selected based on proprietary insights on RORgamma agonist mechanisms, bioinformatics, and input from global immuno-oncology experts.
"We are excited with the rapid progress of our RORgamma program, which recently reported favorable preliminary safety findings and promising clinical activity from the Phase 1 portion of the study," said Paul Sekhri, President and CEO of Lycera. "With two product programs in Phase 2 testing, LYC-55716 as well as our novel ATPase modulator LYC-30937-EC (Enteric Coated), we continue our leadership in the advancement of selective small molecule immune modulators that address unmet needs among broad patient populations."
The Phase 2a expansion trial is focused on detecting signals of clinical activity in six tumor cohorts selected based on a unique insights that Lycera brought to understanding the mechanism of action of the RORg agonist and other selected criteria related to immuno-oncology. Based on current timelines, the Phase 2a portion of the ARGON trial is expected to complete patient enrollment by mid-2018.
The ARGON trial (Trial of RORgamma Agonist LYC-55716 in Advanced Cancer) is a Phase 1/2a study of LYC-55716 in patients with advanced, relapsed or refractory solid tumors. The initial Phase 1 portion of the study enrolled a total of 32 patients, and was designed to find the biologically active or maximum tolerated dose (MTD) of LYC-55716. The study is utilizing a 3+3 study design, in which LYC-55716 is administered orally in subjects with relapsed or refractory solid tumors. The primary endpoints are safety and tolerability and determination of the recommended Phase 2a dose, while secondary endpoints include objective responses according to response evaluation criteria in solid tumors (RECIST) v1.1 criteria. Based upon determination of the recommended Phase 2a dose, LYC-55716 entered Phase 2a, which is expected to enroll approximately 75 patients. The primary efficacy endpoint of the Phase 2a portion of the study will be objective response rate according to RECIST.
In September 2017, Lycera reported favorable preliminary safety data and promising clinical activity with long-term disease stabilization in heavily pretreated patient population from the Phase 1 portion of the ARGON study at the European Society for Medical Oncology (ESMO) Congress, Madrid, Spain. Findings from the first three cohorts (N=15) in the Phase 1 portion demonstrated that LYC-55716 was well-tolerated and there were no treatment-related serious adverse events during the trial's 28-day treatment period and beyond. In the first two cohorts (N=11) eligible for response assessment, 4 patients were observed to have long-term stable disease (SD), including 2 patients with disease stabilization for greater than 7 months who remained on treatment at the time of the presentation.
LYC-55716 is a first in class oral, selective RORgamma agonist. The retinoic acid-related orphan receptor gamma (RORgamma) is a nuclear receptor transcription factor that acts as an immune cell master control switch. RORgamma agonists modulate gene expression to reprogram immune cells for improved function, as well as decrease immunosuppressive mechanisms, resulting in decreased tumor growth and enhanced survival in in vivo preclinical models of cancer.