Related Experiment Video

Updated: Jan 28, 2026

Evaluation of the In vivo Antitumor Activity of Polyanhydride IL-1α Nanoparticles
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Evaluation of the In vivo Antitumor Activity of Polyanhydride IL-1α Nanoparticles

Published on: June 28, 2021

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Phase 1 Open-Label, Multicenter Study of First-in-Class RORγ Agonist LYC-55716 (Cintirorgon): Safety, Tolerability,

Devalingam Mahalingam1, Judy S Wang2, Erika P Hamilton3

  • 1Department of Medicine, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|March 2, 2019
PubMed
Abstract

Insights

The RORγ agonist LYC-55716 (cintirorgon) demonstrated good safety and tolerability in a phase 1 study for advanced cancers. This supports further investigation of this novel immune modulator in a phase 2a trial.

Area of Science:

  • Immunology
  • Oncology
  • Pharmacology

Background:

  • Retinoic acid receptor-related orphan receptor γ (RORγ) is a key transcription factor regulating type 17 effector T-cell differentiation and immune responses.
  • Synthetic RORγ agonists can modulate immune cell gene expression, potentially enhancing anti-tumor immunity and reducing immune suppression.

Purpose of the Study:

  • To evaluate the safety and tolerability of LYC-55716 (cintirorgon), a novel oral RORγ agonist, in adults with relapsed/refractory metastatic cancer.
  • To determine the optimal dose for future clinical trials based on pharmacokinetic and safety profiles.

Main Methods:

  • A phase 1, dose-escalation study of oral LYC-55716 in 32 patients with advanced cancers.
  • Treatment cycles of 28 days, with dose and regimen determined by pharmacokinetic and safety assessments.
  • Primary endpoints: safety and tolerability; Secondary endpoints: pharmacokinetics and objective tumor response rate.

Main Results:

  • No dose-limiting toxicities were observed across the dose range of 150 mg to 450 mg BID.
  • Treatment-related adverse events were mostly grade 1-2, with diarrhea and fatigue being most common. Grade 3 events included anemia and elevated liver enzymes.
  • Pharmacokinetic and pharmacodynamic analyses confirmed RORγ pathway engagement. Two partial responses and disease stabilization in 11 patients were observed.

Conclusions:

  • LYC-55716 (cintirorgon) exhibits a favorable safety and tolerability profile in patients with advanced cancers.
  • The 450 mg BID dose was selected for a phase 2a study to further assess clinical activity, safety, and biomarkers in various cancer types.

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