American Association for Cancer Research
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Supplementary Figure 4 from Activating Inducible T cell Co-stimulator (ICOS) yields anti-tumor activity alone and in combination with anti-PD-1 checkpoint blockade

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journal contribution
posted on 2023-07-19, 13:00 authored by Sapna Yadavilli, Jeremy D Waight, Sara Brett, Meixia Bi, Tianqian Zhang, Yao-Bin Liu, Catherine Ellis, David C Turner, Ashleigh Hahn, Hong Shi, Laura Seestaller-Wehr, Junping Jing, Qing Xie, Jafar Sadik Shaik, Xiao Ji, Robert Gagnon, William Fieles, Laura Hook, Steven Grant, Stephanie Hopley, M. Phillip DeYoung, Christina Blackwell, Michael Chisamore, Robert Biddlecombe, David J Figueroa, Christopher B Hopson, Roopa Srinivasan, James Smothers, Michele Maio, Danny Rischin, Daniel Olive, Elaine Paul, Patrick A. Mayes, Axel Hoos, Marc Ballas

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In recent years there has been considerable interest in monoclonal antibody (mAb)-based induction of co-stimulatory receptor signaling as an approach to combat cancer. However, promising nonclinical data have yet to translate to a meaningful clinical benefit. Inducible T cell co-stimulator (ICOS) is a co-stimulatory receptor important for immune responses. Using a novel clinical-stage anti-ICOS immunoglobulin G4 mAb (feladilimab), which induces but does not deplete ICOS+ T cells and their rodent analogs, we provide an end-to-end evaluation of the antitumor potential of antibody-mediated ICOS co-stimulation alone and in combination with programmed cell death protein 1 (PD-1) blockade. We demonstrate, consistently, that ICOS is expressed in a range of cancers, and its induction can stimulate growth of antitumor reactive T cells. Further, feladilimab, alone and with a PD-1 inhibitor, induced antitumor activity in mouse and humanized tumor models. In addition to nonclinical evaluation, we present three patient case studies from a first-time-in-human, phase 1, open label, dose escalation and dose expansion clinical trial (INDUCE-1; NCT02723955), evaluating feladilimab alone and in combination with pembrolizumab in patients with advanced solid tumors. Preliminary data showing clinical benefit in patients with cancer treated with feladilimab alone or in combination with pembrolizumab was reported previously; with example cases described here. Additional work is needed to further validate the translation to the clinic, which includes identifying select patient populations that will benefit from this therapeutic approach, and randomized data with survival endpoints to illustrate its potential, similar to that shown with CTLA-4 and PD-1 blocking antibodies.