Results from a first-in-man, open label, safety and tolerability trial of CAN04 (nidanilimab), a fully humanized monoclonal antibody against the novel antitumor target, IL1RAP, in patients with solid tumor malignancies.

person Ahmad Awada Institut Jules Bordet, Brussels, Belgium info_outline Ahmad Awada, Ferry Eskens, Debbie Robbrecht, Ulrik Niels Lassen, Morten Mau Soerensen, Neeltje Steeghs, Christiane Jungels, Philippe Georges Aftimos, Signe Øien Fretland, Lars Thorsson, Tormod Kyrre Guren

Authors person Ahmad Awada Institut Jules Bordet, Brussels, Belgium info_outline Ahmad Awada, Ferry Eskens, Debbie Robbrecht, Ulrik Niels Lassen, Morten Mau Soerensen, Neeltje Steeghs, Christiane Jungels, Philippe Georges Aftimos, Signe Øien Fretland, Lars Thorsson, Tormod Kyrre Guren Organizations Institut Jules Bordet, Brussels, Belgium, Erasmus MC Cancer Institute, Rotterdam, Netherlands, Erasmus MC, Rotterdam, Netherlands, Department of Oncology, Rigshospitalet, Copenhagen, Denmark, Netherlands Cancer Institute, Amsterdam, Netherlands, Institut Jules Bordet, Unversité Libre de Bruxelles, Brussels, Belgium, Medical Oncology Clinic, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium, Oslo University Hospital, Oslo, Norway, Cantargia AB, Lund, Sweden Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Background: Interleukin 1 receptor Accessory protein, IL1RAP, is expressed in several solid tumors, both on cancer cells and tumor-associated inflammatory cells. CAN04 is a first-in-class fully humanized monoclonal antibody targeting IL1RAP blocking IL-1 alpha and beta signaling and triggering antibody dependent cellular cytotoxicity. Methods: The primary objective was to assess safety and tolerability of weekly CAN04 in order to define the Recommended Phase 2 Dose (RP2D). Patients (pts) with relapsed or refractory non-small cell lung cancer (NSCLC), pancreatic ductal adenocarcinoma (PDAC), breast or colorectal cancer were included using a 3+3 dose escalation design. Key eligibility criteria were ECOG ≤1, normal organ function and no bleeding disorder/coagulopathy. Tumor responses were evaluated according to irRC every 8 weeks. PK and biomarkers were analyzed in serum. Results: 22 pts were enrolled across 5 cohorts (1-10 mg/kg). Demography: mean age 62 yrs (39-81); gender 14 M and 8 F; median number of prior lines of therapy 3 (range 1-11). AEs occurred mainly following the first dose and the most common AEs were: infusion related reaction (IRR) (41%), pyrexia (27%), fatigue (23%), chills (23%) and nausea (23%). AE grade 3 or 4: one IRR, one neutropenia/leukopenia and one hypokalemia, all of them grade 3. Serum CRP and IL-6 were reduced after two weeks of treatment. There were linear increases of AUC and Cmax (1-10 mg/kg) and CAN04 exposure at 10mg/kg was above levels associated with signs of efficacy in preclinical models. In pts receiving at least one dose of CAN04, 9/20 (45%) had SD by irRC (7/20 had SD by RECIST 1.1) at 8 weeks follow up. Two pts, one with NSCLC and one with PDAC, had SD for 6 and 4 months (latter still on therapy). Conclusions: CAN04 demonstrated a manageable safety profile and a RP2D of 10 mg/kg has been established. The dose expansion phase of the trial will evaluate CAN04 as monotherapy as well as in combination with relevant chemotherapy regimens in NSCLC and PDAC in separate arms. Clinical trial information: NCT03267316