Missing content? – Request curation!
Request curation for specific Genes, variants, or PubMed publications.
Have questions, comments or suggestions? - Let us know!
Email us at : email@example.com
|Ref Type||Journal Article|
|Authors||Mahalingam D, Wang JS, Hamilton EP, Sarantopoulos J, Nemunaitis J, Weems G, Carter L, Hu X, Schreeder M, Wilkins HJ|
|Title||Phase 1 Open-Label, Multicenter Study of First-in-Class RORγ Agonist LYC-55716 (Cintirorgon): Safety, Tolerability, and Preliminary Evidence of Antitumor Activity.|
|Journal||Clinical cancer research : an official journal of the American Association for Cancer Research|
|Date||2019 06 15|
|Abstract Text||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 (cintirorgon), a first-in-class, oral, small-molecule RORγ agonist in adults with relapsed/refractory metastatic cancer.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.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 gamma-glutamyl 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).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.|
|Molecular Profile||Treatment Approach|
|Gene Name||Source||Synonyms||Protein Domains||Gene Description||Gene Role|
|Therapy Name||Drugs||Efficacy Evidence||Clinical Trials|
|Drug Name||Trade Name||Synonyms||Drug Classes||Drug Description|
|LYC-55716||Cintirorgon|LYC55716||Cintirorgon (LYC-55716) is a retinoic acid-related orphan receptor gamma agonist, which may increase T-cell mediated anti-tumor immune response, potentially leading to inhibition of tumor growth (AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5566, PMID: 30819679).|
|Gene||Variant||Impact||Protein Effect||Variant Description||Associated with drug Resistance|
|Molecular Profile||Indication/Tumor Type||Response Type||Therapy Name||Approval Status||Evidence Type||Efficacy Evidence||References|
|Unknown unknown||lung non-small cell carcinoma||not applicable||LYC-55716||Case Reports/Case Series||Actionable||In a Phase I trial, Cintirorgon (LYC-55716) treatment resulted in a partial response in a patient with non-small cell lung cancer who was previously treated with Keytruda (pembrolizumab) and had progressed (PMID: 30819679).||30819679|
|Unknown unknown||Advanced Solid Tumor||not applicable||LYC-55716||Phase I||Actionable||In a Phase I trial, Cintirorgon (LYC-55716) treatment resulted in a partial response in 8% (2/25) and stable disease in 44% (11/25) of patients with an advanced solid tumor, with stable disease lasting 2 to 12 months (PMID: 30819679).||30819679|
|Unknown unknown||spindle cell carcinoma||not applicable||LYC-55716||Case Reports/Case Series||Actionable||In a Phase I trial, Cintirorgon (LYC-55716) treatment resulted in a partial response in a patient with metastatic spindle cell carcinoma, demonstrating decreased tumor burden (PMID: 30819679).||30819679|