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Supplementary Data from First-in-Human Phase I/II ICONIC Trial of the ICOS Agonist Vopratelimab Alone and with Nivolumab: ICOS-High CD4 T-Cell Populations and Predictors of Response

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posted on 2023-03-31, 23:49 authored by Timothy A. Yap, Justin F. Gainor, Margaret K. Callahan, Gerald S. Falchook, Russell K. Pachynski, Patricia LoRusso, Shivaani Kummar, Geoffrey T. Gibney, Howard A. Burris, Scott S. Tykodi, Osama E. Rahma, Tanguy Y. Seiwert, Kyriakos P. Papadopoulos, Mariela Blum Murphy, Haeseong Park, Amanda Hanson, Yasmin Hashambhoy-Ramsay, Lara McGrath, Ellen Hooper, Xiaoying Xiao, Heather Cohen, Martin Fan, Daniel Felitsky, Courtney Hart, Rachel McComb, Karen Brown, Ali Sepahi, Judith Jimenez, Weidong Zhang, Johan Baeck, Haley Laken, Richard Murray, Elizabeth Trehu, Christopher J. Harvey
Supplementary Data from First-in-Human Phase I/II ICONIC Trial of the ICOS Agonist Vopratelimab Alone and with Nivolumab: ICOS-High CD4 T-Cell Populations and Predictors of Response

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NIH

NCI

Clinical Translational Science Award

Cancer Prevention Research Institute of Texas

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ARTICLE ABSTRACT

The first-in-human phase I/II ICONIC trial evaluated an investigational inducible costimulator (ICOS) agonist, vopratelimab, alone and in combination with nivolumab in patients with advanced solid tumors. In phase I, patients were treated with escalating doses of intravenous vopratelimab alone or with nivolumab. Primary objectives were safety, tolerability, MTD, and recommended phase II dose (RP2D). Phase II enriched for ICOS-positive (ICOS+) tumors; patients were treated with vopratelimab at the monotherapy RP2D alone or with nivolumab. Pharmacokinetics, pharmacodynamics, and predictive biomarkers of response to vopratelimab were assessed. ICONIC enrolled 201 patients. Vopratelimab alone and with nivolumab was well tolerated; phase I established 0.3 mg/kg every 3 weeks as the vopratelimab RP2D. Vopratelimab resulted in modest objective response rates of 1.4% and with nivolumab of 2.3%. The prospective selection for ICOS+ tumors did not enrich for responses. A vopratelimab-specific peripheral blood pharmacodynamic biomarker, ICOS-high (ICOS-hi) CD4 T cells, was identified in a subset of patients who demonstrated greater clinical benefit versus those with no emergence of these cells [overall survival (OS), P = 0.0025]. A potential genomic predictive biomarker of ICOS-hi CD4 T-cell emergence was identified that demonstrated improvement in clinical outcomes, including OS (P = 0.0062). Vopratelimab demonstrated a favorable safety profile alone and in combination with nivolumab. Efficacy was observed only in a subset of patients with a vopratelimab-specific pharmacodynamic biomarker. A potential predictive biomarker of response was identified, which is being prospectively evaluated in a randomized phase II non–small cell lung cancer trial.See related commentary by Lee and Fong, p. 3633

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    Clinical Cancer Research

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    cancer

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