Abstract CT035: ICONIC: Phase 1/2 trial of ICOS agonist JTX-2011 alone and in combination with nivolumab (nivo)
Authors: Sears Olivia , Burris Howard , Tolcher Anthony , Callahan Margaret , Yap Timothy , Kummar Shivanni , Falchook Gerald , Pachynski Russell , Tykodi Scott , Siewert Tanguy , Gibney Geoffrey , Gainor Justin , LoRusso Patricia , Lazaro Emmanuel , Clancy Myles , Li Ella , Ding Baoyu , Trehu Elizabeth 
Published: July 2017

Abstract
Background: JTX-2011 is an agonist monoclonal antibody that targets ICOS, Inducible CO-Stimulator of T cells. A dual mechanism of action is intended to induce proliferation and stimulation of CD4 T effector cells and selectively deplete intratumoral T regulatory cells. JTX-2011 has shown preclinical antitumor effects both as a single agent and in combination with anti-PD-1 antibodies, with single agent efficacy correlated with % of ICOS expressing T cells in tumors. An ICOS IHC assay was used to identify human tumor types with the highest levels of ICOS expressing T cells.
Methods: ICONIC is a first-in-human Phase 1/2, open label, adaptive clinical study of JTX-2011 alone or in combination with a fixed dose of nivo in subjects with advanced solid tumors. It is designed to assess safety and tolerability, determine the maximal tolerated dose (MTD) and recommended Phase 2 dose, and evaluate preliminary efficacy.
Part A: 3+3 dose escalation of JTX-2011, with Safety/PK/PD expansion cohorts at 2 or more dose levels.
Part B: 3+3 dose escalation of JTX-2011 in combination with nivo, with Safety/PK/PD expansion cohorts at two or more dose levels.
Part C: ≥3 JTX-2011 cohorts in tumors expected to have higher levels of ICOS expressing T cells (non small cell lung cancer [NSCLC], head and neck squamous cell cancer [HNSCC], and others), with ICOS enrichment by IHC.
Part D: ≥ 5 JTX-2011 + nivo cohorts in tumors expected to have higher levels of ICOS expressing T cells NSCLC, HNSCC, triple negative breast cancer, melanoma, gastric, and others), with ICOS enrichment by IHC.
Major Inclusion Criteria
Confirmed cancer that is recurrent, metastatic, or persistent after at least one line of therapy and with no further standard treatment optionsA&B: available and consent to provide archival tumor tissueC&D: available and consent to provide archival tumor tissue, have a lesion that can be biopsied at acceptable clinical risk (as judged by the investigator), and agree to a fresh biopsy
Major Exclusion Criteria
Refused standard therapy Hx of intolerance, hypersensitivity, or treatment discontinuation due to severe immune adverse events on prior immunotherapyImmunodeficiencyActive or prior history of autoimmune diseaseSymptomatic or uncontrolled brain metastases, leptomeningeal disease, or spinal cord compression
Endpoints
Safety and tolerability PK, target engagement, and other PD markers Efficacy by RECIST 1.1 and irR
Overall response rateDuration of ResponseDisease Control RateProgression Free Survival (PFS)Landmark PFSOverall Survival
Trial Progress
Enrollment began in August 2016 and is continuing as planned.
Citation Format: Olivia Sears, Howard Burris, Anthony Tolcher, Margaret Callahan, Timothy Yap, Shivanni Kummar, Gerald Falchook, Russell Pachynski, Scott Tykodi, Tanguy Siewert, Geoffrey Gibney, Justin Gainor, Patricia LoRusso, Emmanuel Lazaro, Myles Clancy, Ella Li, Baoyu Ding, Elizabeth Trehu. ICONIC: Phase 1/2 trial of ICOS agonist JTX-2011 alone and in combination with nivolumab (nivo) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr CT035. doi:10.1158/1538-7445.AM2017-CT035