Abstract 196TiP
Background
REGN6569 is a fully human immunoglobulin G1 mAb that is highly specific for glucocorticoid-induced tumour necrosis factor receptor–related protein (GITR). GITR is expressed on several immune cell subtypes, notably regulatory T cells (Tregs). REGN6569 has demonstrated in vitro antibody-dependent cell-mediated cytotoxicity (ADCC) with greater cytotoxicity against GITR expressing Tregs than CD8+ T cells. GITR mAbs have shown preclinical antitumour efficacy. Anti-GITR and anti–programmed cell death-1 (PD-1) combination therapy has synergistic biological activity and may optimise immune checkpoint inhibitor (ICI) treatment in patients with advanced solid tumours.
Trial Design
This ongoing first-in-human study (NCT04465487) will assess safety, tolerability, pharmacokinetics, pharmacodynamics and antitumour activity of REGN6569 in combination with cemiplimab (anti-PD-1) in patients with advanced solid tumours, for which ICI therapies have not been approved or are not available. Patients must be at least 18 years old, have Eastern Cooperative Oncology Group performance status (0 or 1), and be naive to ICIs. The study includes dose-escalation (a “4+3” design; in advanced solid tumours) and dose-expansion (in patients with advanced head and neck squamous cell carcinoma) parts. The dose-escalation part will cover 5 dose levels (DL1-DL5) for REGN6569, administered intravenously (IV) every 3 weeks (Q3W). Patients will receive REGN6569 as monotherapy lead-in for the first dose followed by REGN6569 in combination with standard cemiplimab 350 mg IV Q3W. Dose expansion will open after review of safety, efficacy and pharmacodynamic data from the dose-escalation phase. The primary objective of the dose-escalation phase is to evaluate safety and tolerability. The co-primary objectives of the dose-expansion phase are to assess preliminary efficacy of REGN6569 in combination with cemiplimab, as measured by objective response rate, and preliminary pharmacodynamic activity of REGN6569 as lead-in monotherapy, as measured by intratumoural GITR+ Treg depletion. The study is currently open to enrolment.
Clinical trial identification
NCT04465487.
Editorial acknowledgement
Medical writing support was provided by Sameen Yousaf, PhD, of Prime, Knutsford, UK, funded by Regeneron Pharmaceuticals, Inc. Responsibility for all opinions, conclusions, and data interpretation lies with the authors.
Legal entity responsible for the study
Regeneron Pharmaceuticals, Inc.
Funding
Regeneron Pharmaceuticals, Inc.
Disclosure
N. Lakhani: Financial Interests, Personal, Advisory Role: Innovent Biologics; Financial Interests, Institutional, Research Grant: Alexion Pharmaceuticals, Alexo Therapeutics, Alpine Immune Sciences, Alpine Immune Sciences, Apexian Pharmaceuticals, Asana Biosciences, Ascentage Pharma, Astellas Pharma, BeiGene, Celgene, Cerulean Pharma, Constellation Pharmaceuticals, Coordination Ther. O. Hamid: Financial Interests, Personal, Other, Honoraria: Bristol Myers Squibb, Novartis, Pfizer, Sanofi and Regeneron Pharmaceuticals, Inc; Financial Interests, Personal, Advisory Role: Aduro Biotech, Akeso Biopharma, Amgen, Arcus Biosciences, Bioatla, Bristol Myers Squibb, CytomX Therapeutics, Exelixis, Genentech, GlaxoSmithKline, Idera, Immunocore, Incyte, Iovance Biotherapeutics, Merck, Merck Serono, Moderna Therapeutics, NextCure, No. I. Braña: Financial Interests, Personal, Other, Financial interests: Bicycle Therapeutics, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Debiopharm, Dragonfly therapeutics, GlaxoSmithKline, Gliknik, Immutep, Incyte, ISA pharmaceuticals, Janssen Oncology, Kura, MacroGenics, Merck Serono, Merck Sharp & Dohme (MSD), Na; Financial Interests, Personal, Advisory Board: Achilles Therapeutics, Rakuten Pharma, PCI Biotech, Merck Sharp & Dohme (MSD), eTheRNA Immunotherapies, Bristol Myers Squibb, AstraZeneca. P.L. Swiecicki: Financial Interests, Institutional, Research Grant: Ascentage Pharma and Pfizer; Financial Interests, Personal, Advisory Board: Prelude Therapeutics, Elevar Therapeutics, and Regeneron Pharmaceuticals. M.J. De Miguel Luken: Financial Interests, Personal, Advisory Board: Syneos; Financial Interests, Personal, Other, Educational fees: Roche, Janssen, MSD . H. Khong: Financial Interests, Personal, Advisory Board: Celcuity; Financial Interests, Institutional, Research Grant: AstraZeneca. V. Moreno Garcia: Financial Interests, Personal, Advisory Role: Bayer, Basilea Pharmaceuticals, Bristol Myers Squibb, Janssen and Pieris. M.J. Lostes Bardaji: Financial Interests, Personal, Advisory Role: Bayer, Basilea Pharmaceuticals, Bristol Myers Squibb, Janssen and Pieris. F. Sun: Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc. S. Sandigursky: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. M. Zambrano: Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc. M. Cristea: Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc. M. Fury: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. All other authors have declared no conflicts of interest.