Phase 1 open-label, multicenter study of first-in-class RORγ agonist LYC-55716 (Cintirorgon): Safety, tolerability, and preliminary evidence of antitumor activity

Devalingam Mahalingam, Judy S. Wang, Erika P. Hamilton, John Sarantopoulos, John Nemunaitis, Garry Weems, Laura Carter, Xiao Hu, Marshall Schreeder, H. Jeffrey Wilkins

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1 Scopus citations


Purpose: Transcription factor retinoic acid receptor-related orphan receptor γ (RORγ) regulates type 17 effector T-cell differentiation and function and is key to immune cell regulation. Synthetic RORγ agonists modulate immune cell gene expression to increase effector T-cell activity and decrease immune suppression. A phase 1 study evaluated the safety and tolerability of LYC-55716 (cintiRORγon), a first-in-class, oral, small-molecule RORγ agonist in adults with relapsed/ refractory metastatic cancer. Patients and Methods: Patients received 28-day treatment cycles of oral LYC-55716; dose and dosing regimen were determined according to pharmacokinetic profile and safety. Primary endpoints were safety and tolerability. Secondary endpoints included pharmacokinetics and objective tumor response rate. Results: No dose-limiting toxicities occurred among the 32 enrolled patients who received LYC-55716 150 mg BID to 450 mg BID. Treatment-related adverse events (AE) were primarily grade 1-2 and included diarrhea (n = 11), fatigue (n=7), anemia (n=4), decreased appetite (n=4), and nausea (n = 4). Grade 3 AEs were anemia (n = 2), elevated gammaglutamyl transferase (n = 1), and hypophosphatemia (n = 1). Pharmacokinetic concentrations achieved levels expected for target gene regulation. Pharmacodynamic results indicated RORγ pathway engagement. Two patients (NSCLC and sarcomatoid breast cancer) had confirmed partial responses; 11 had disease stabilization for 2 to 12 months (6 received >4 months of treatment). Conclusions: These data support the safety and tolerability of LYC-55716 and selection of 450 mg BID dose for a phase 2a study assessing LYC-55716 clinical activity, safety, and biomarkers in patients with NSCLC, head and neck, gastroesophageal, renal cell, urothelial, and ovarian cancers.

Original languageEnglish (US)
Pages (from-to)3508-3516
Number of pages9
JournalClinical Cancer Research
Issue number12
StatePublished - Jun 15 2019


ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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