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
| العنوان: | 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 |
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| المؤلفون: | Debbie Robbrecht, Christiane Jungels, Morten Mau Sorensen, Iben Spanggaard, Ferry Eskens, Signe Ø Fretland, Tormod Kyrre Guren, Philippe Aftimos, David Liberg, Christer Svedman, Lars Thorsson, Neeltje Steeghs, Ahmad Awada |
| المساهمون: | Medical Oncology |
| المصدر: | British Journal of Cancer, 126(7), 1010-1017. Nature Publishing Group Br J Cancer |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Cancer Research, Oncology, Dose-Response Relationship, Drug, Maximum Tolerated Dose, SDG 3 - Good Health and Well-being, Neoplasms, Antibodies, Monoclonal, Humans, Antineoplastic Agents, Interleukin-1 Receptor Accessory Protein, Article |
| الوصف: | 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. |
| اللغة: | English |
| تدمد: | 0007-0920 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d36fe8599641d77b894744932ed8951a https://pure.eur.nl/en/publications/85dcc1fa-305e-46a4-889d-c10cef4ff14a |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....d36fe8599641d77b894744932ed8951a |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 00070920 |
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