First-in-human phase 1 dose-escalation study of CAN04, a first-in-class interleukin-1 receptor accessory protein (IL1RAP) antibody in patients with solid tumours

Debbie Robbrecht*, Christiane Jungels, Morten Mau Sorensen, Iben Spanggaard, Ferry Eskens, Signe Fretland, Tormod Kyrre Guren, Philippe Aftimos, David Liberg, Christer Svedman, Lars Thorsson, Neeltje Steeghs, Ahmad Awada

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

15 Citations (Scopus)

Abstract

Background: Interleukin-1 (IL-1) signalling is involved in various protumoural processes including proliferation, immune evasion, metastasis and chemoresistance. CAN04 is a first-in-class monoclonal antibody that binds IL-1 receptor accessory protein (IL1RAP), required for IL-1 signalling. In this first-in-human phase 1 study, we assessed safety, recommended phase 2 dose (RP2D), pharmacokinetics, pharmacodynamics and preliminary anti-tumour activity of CAN04 monotherapy. Methods: Patients with advanced solid tumours known to express IL1RAP and refractory to standard treatments were enrolled in a dose-escalation study with 5 dose levels (1.0–10.0 mg/kg) of weekly CAN04. Results: Twenty-two patients were enrolled. Most common adverse events were infusion-related reactions (41%), fatigue (32%), constipation (27%), diarrhoea (27%), decreased appetite (23%), nausea (23%) and vomiting (23%). One dose limiting toxicity was reported. No maximum tolerated dose was identified. Pharmacokinetics analyses indicate higher exposures and slower elimination with increasing doses. Decreases in serum IL-6 and CRP were observed in most patients. Twenty-one patients were evaluable for response, 43% had stable disease per immune-related response criteria with no partial/complete responses. Conclusions: The IL1RAP targeting antibody CAN04 can be safely administered to patients up to 10.0 mg/kg weekly, which was defined as the RP2D. Serum biomarkers supported target engagement and IL-1 pathway inhibition. Clinical trial registration: NCT03267316.

Original languageEnglish
Pages (from-to)1010-1017
Number of pages8
JournalBritish Journal of Cancer
Volume126
Issue number7
Early online date13 Dec 2021
DOIs
Publication statusPublished - 1 Apr 2022

Bibliographical note

Funding Information: This work was supported by Cantargia. Supplementary information is available at the British Journal of Cancer’s website.

Publisher Copyright: © 2021, The Author(s), under exclusive licence to Springer Nature Limited.

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