TY - JOUR
T1 - 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
AU - Robbrecht, Debbie
AU - Jungels, Christiane
AU - Sorensen, Morten Mau
AU - Spanggaard, Iben
AU - Eskens, Ferry
AU - Fretland, Signe
AU - Guren, Tormod Kyrre
AU - Aftimos, Philippe
AU - Liberg, David
AU - Svedman, Christer
AU - Thorsson, Lars
AU - Steeghs, Neeltje
AU - Awada, Ahmad
N1 - 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.
PY - 2022/4/1
Y1 - 2022/4/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85121034856&partnerID=8YFLogxK
U2 - 10.1038/s41416-021-01657-7
DO - 10.1038/s41416-021-01657-7
M3 - Article
C2 - 34903842
AN - SCOPUS:85121034856
SN - 0007-0920
VL - 126
SP - 1010
EP - 1017
JO - British Journal of Cancer
JF - British Journal of Cancer
IS - 7
ER -