1748 - Novel Small-Molecule ROR_ Agonist Immuno-oncology Agent LYC-55716: Safety and Efficacy in a Phase 2A Open-Label, Multicenter Trial

Background

LYC-55716 is a first-in-class, oral, small-molecule investigational agent that selectively activates retinoic acid receptor–related orphan receptor γ (RORγ). Preclinical studies suggest LYC-55716 reduces tumor growth and enhances survival by altering immune cell anti-tumor effector functions and immunosuppressive mechanisms. Results from the Phase 1 portion of an ongoing Phase 1/2A trial showed that LYC-55716 was well tolerated, with no dose-limiting toxicities. The trial also provided qualitative evidence of pharmacodynamic target engagement and multiple patients had disease stabilization, including patients with tumor reduction and a confirmed partial response in a patient with non–small cell lung cancer (NSCLC). The Phase 2A portion of the trial is currently recruiting patients with advanced NSCLC, head and neck (SCCHN), gastroesophageal (GE), renal cell (RCC), urothelial (UC), and ovarian (OC) cancers.

Methods

The Phase 2A portion is enrolling ∼75 adult patients who receive 28-day treatment cycles of LYC-55716 administered twice daily. The primary endpoint is evaluation of the objective response rate (ORR), determined via response evaluation criteria in solid tumors (RECIST) v1.1. Secondary endpoints include duration of response, safety, and pharmacokinetics. Immune-related biomarkers are being assessed in blood samples from all patients and in tissue biopsy samples of selected patients, using a NanoString platform and immunohistochemistry.

Results

Fifty-six patients have been enrolled as of the time of submission (NSCLC: 17, SCCHN: 4, GE: 10, RCC: 4, UC: 7, and OC: 14) and response assessments are ongoing. Three cases of Grade 3 immune-mediated rash were observed. Updated response assessment, safety, and biomarker data will be presented.

Conclusions

The ongoing Phase 2A trial of the first-in-class small-molecule RORγ agonist LYC-55716 will determine the ORR, duration of response, and effects of treatment on survival and immune biomarkers in patients with advanced NSCLC, SCCHN, GE, RCC, UC, and OC.

Clinical trial identification

NCT02929862.

Legal entity responsible for the study

Lycera Corp.

Funding

Lycera Corp.

Editorial Acknowledgement

Editorial assistance was provided by Autumn Kelly, MA, CMPP, of Simcoe Consultants, Inc, on behalf of Lycera Corp.

Disclosure

J. Wang: Speakers' Bureau: AstraZeneca. S.V. Liu: Consulting or advisory role: Genentech, Pfizer, ARIAD, Celgene, Lilly, Taiho Pharmaceutical, Bristol-Myers Squibb, AstraZeneca, Ignyta, Takeda; Research funding: Genentech/Roche, Pfizer, Threshold Pharmaceuticals, Clovis Oncology, Corvus Pharmaceuticals, Esanex, Bayer, OncoMed, Ignyta, Merck, MedImmune, Lycera Corp., AstraZeneca. H.E. Uronis: Advisory role: Bristol-Myers Squibb; Research funding to institution: Genentech/Roche, Bristol-Myers Squibb, Advaxis, Macrogenics, Merck, and Lycera Corp. C. Wu: Research funding: Amgen; Research funding to institution: Bristol-Myers Squibb, Vaccinex, Boston Biomedical. D. Mahalingam: Advisory roles: Bayer, Amgen, BMS UK; Speakers' Bureaus: Bayer, Amgen, Genentech, BMS UK; Research funding: Merck and Co., Inc. L. Carter, X. Hu, G. Weems, H.J. Wilkins: Employee and shareholder: Lycera Corp. L.R. Duska: Advisory role: Parexel, Advance Medical, ClearView Healthcare Partners, British Journal of Obstetrics and Gynecology, UpToDate, Merck; Research funding to institution: GlaxoSmithKline, Millennium, Bristol-Myers Squibb, Aeterna Zentaris, Novartis, Abbvie, Tesaro, Cerulean Pharma, Aduro Biotech, Advaxis, Syndax, Pfizer, Merck. K. Kelly: Advisory role: AstraZeneca, Ariad, Boehringer Ingelheim, Bristol-Myers Squibb, Genentech/Roche, Lilly, G1 Therapeutics, Regeneron, Abbvie, Janssen; Research funding to institution: Novartis, EMD Serono, Lilly, Genentech, Abbvie, Celgene, Five Prive Therapeutics, Transgene, Lycera Corp., Regeneron. All other authors have declared no conflicts of interest.