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Clinical Studies

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



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.


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.


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.


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


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Fig. 1: IL1RAP is required for both IL-1α and IL-1β signalling.
Fig. 2: Analysis of cytokine levels during first infusion in relation to observed IRR with boxplots on change (ratio) in IL-6, IL-10, IFN-γ and IL2RA from baseline to peak.
Fig. 3: Analysis of relative change in biomarkers at baseline to before the third dose of CAN04, 2 weeks later.

Data availability

The datasets generated and/or analysed during the current study are available from the corresponding author on reasonable request.


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Drafting and editorial support was provided by Satyen Shenoy and Agnieszka Linkiewicz-Zegan on behalf of Proper Medical Writing, Poland.


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

Author information

Authors and Affiliations



DR, CJ, MMS, IS, FE, SØF, TKG, PA, NS and AA participated in patients’ enrolment. DR, DL, CS and LT analysed the data and wrote the manuscript. DL conducted and supervised the preclinical experiments. AA is the coordinating investigator of CANFOUR and participated in the protocol review. All authors reviewed the manuscript, approved the final version and agree to be accountable for all aspects of the work.

Corresponding author

Correspondence to Debbie Robbrecht.

Ethics declarations

Ethics approval and consent to participate

The clinical study protocol and other relevant study documents were approved by the applicable regional review boards/ethic committees (not listed because of limited word space). Written informed consent was obtained from all patients prior to any study related procedure. The study was performed in accordance with the Declaration of Helsinki.

Consent for publication

Not applicable.

Competing interests

DR, CJ, MMS, FE, SØF and TKG report no personal conflict of interest to declare regarding this manuscript. IS reports no personal conflict of interest except for travel expenses and accommodation from Roche. PA reports consulting for Boehringer Ingelheim, Macrogenics, Roche, Novartis, Amcure, Servier, G1 Therapeutics, Radius and Deloitte; honoraria from Synthon, Amgen, Novartis and Gilead; travel grants from Amgen, MSD, Pfizer and Roche. DL and LT are Cantargia employees. CS is a consultant for Cantargia. NS reports consultation or attending advisory boards for AIMM Therapeutics, Boehringer Ingelheim and Ellipses Pharma; receiving research grants for the institute from AB Science, Abbvie, Actuate Therapeutics, Amgen, Array, AstraZeneca/MedImmune, Bayer, Blueprint Medicines, Boehringer Ingelheim, Bristol-Myers Squibb, Cantargia, Cytovation, Deciphera, Genentech/Roche, GlaxoSmithKline, Incyte, InteRNA, Lilly, Merck Sharp & Dohme, Merus, Novartis, Pfizer, Pierre Fabre, Roche, Sanofi, Taiho and Takeda (outside the submitted work). AA reports advisory role, research grants to the Institute and speaker fees from: Roche, Lilly, Amgen, EISAI, BMS, Pfizer, Novartis, MSD, Genomic Health, Ipsen, AstraZeneca, Bayer and Leo Pharma. Erasmus MC Cancer Institute, Rotterdam, was financially supported by Cantargia to perform their part of this clinical trial. Department of Oncology, Rigshospitalet, Copenhagen, collaborates and received research funding from: AstraZeneca, Bristol-Myers Squibb, Loxo/Lilly, Alligator Bioscience, Cantargia, Incyte, Pfizer, Orion, Roche, MSD, Genentech, Loxa/Bayer, Symphogen, Puma Biotechnology, Genmab, and Novartis. Institut Jules Bordet—Université Libre de Bruxelles, Brussels, received research funding from Roche.

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Robbrecht, D., Jungels, C., Sorensen, M.M. et al. 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. Br J Cancer 126, 1010–1017 (2022).

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