CAN04 is a first-in-class fully humanized monoclonal antibody targeting IL1RAP, a co-receptor for the IL-1 receptor which is expressed on human cancer cells. CAN04 binds to IL1RAP with high affinity in a manner that blocks signal transduction from IL-1 and IL-33 into the cells. Binding of CAN04 to IL1RAP also allows NK-cells to recognize tumor cells and subsequent killing by antibody dependent cellular cytotoxicity (ADCC).
The primary objective was to assess safety and tolerability of weekly CAN04 in order to define the Maximum Tolerated Dose/Recommended Phase 2 Dose. Patients with relapsed or refractory non-small cell lung cancer (NSCLC), pancreatic ductal adenocarcinoma (PDAC), breast or colorectal cancer were included in the initial part of the trial using a 3 + 3 dose escalation design. Key eligibility criteria were ECOG ≤1, normal organ function and no bleeding disorder or coagulopathy. Tumor responses were evaluated according to irRC every 8 weeks. Plasma samples were obtained for pharmacokinetic evaluation and for assessment of circulatory biomarkers of immunological activity (e g IL-1α, IL-1β, IL-1RA, IL-6, IL-8, IL-33 and TNF-α).
Nine subjects were enrolled across 3 initial cohorts (1-3 mg/kg). Demography: mean age 66 yrs (48-77); gender 5 M and 4 F; median number of prior lines of therapy 5 (range 2-11). No dose limiting toxicities (DLTs) were observed and MTD has not been reached yet. AEs occurred mainly following the first dose and the most common AEs were: fatigue (67%), nausea (44%), pyrexia (44%), infusion related reaction (IRR) (44%) and pruritus (44%). AE grade 3 or 4: one grade 3 IRR following an initial dose of 1.0 mg/kg in cohort 3. Stable disease was achieved in 2/6 and progressive disease in 4/6 patients after 8 weeks of treatment.
CAN04 demonstrated a manageable safety profile in the initial 3 cohorts with no DLTs observed and the dose escalation will be continued as planned. The dose expansion phase of the trial will then evaluate CAN04 as monotherapy as well as in combination with standard of care therapy for NSCLC and PDAC in separate arms.
Clinical trial identification
Legal entity responsible for the study
A. Awada: Honorarium for advisory board: Cantargia AB. P.G. Aftimos: Honoraria: Synthon, Boehringer Ingelheim, Macrogenics, Amgen, Novartis; Travel grants: Amgen, Merck, Roche. L. Thorsson: Employee and shareholder: Cantargia AB. All other authors have declared no conflicts of interest.