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Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

4992 - A first-in-class, first-in-human phase I/IIa trial of CAN04, targeting Interleukin-1 Receptor Accessory Protein (IL1RAP), in patients with solid tumors

Date

20 Oct 2018

Session

Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

Topics

Clinical Research;  Cytotoxic Therapy

Tumour Site

Presenters

Ahmad Awada

Citation

Annals of Oncology (2018) 29 (suppl_8): viii400-viii441. 10.1093/annonc/mdy288

Authors

A. Awada1, F.A.L.M. Eskens2, D.G. Robbrecht2, U.N. Lassen3, M. Sorensen3, J.H.M. Schellens4, J.S. de Groot4, C. Jungels1, P.G. Aftimos1, S.O. Fretland5, L. Thorsson6, T.K. Guren5

Author affiliations

  • 1 Medical Oncology Clinic, Institut Jules Bordet, Université Libre de Bruxelles, 1000 - Brussels/BE
  • 2 Department Of Medical Oncology, Erasmus MC Cancer Institute, 3015 CE - Rotterdam/NL
  • 3 Onkologisk Klinik/dept. Of Oncology, Rigshospitalet, Copenhagen University Hospital, 2100 - Copenhagen/DK
  • 4 Division Of Clinical Pharmacology, Department Of Medical Oncology, The Netherlands Cancer Institute, Amsterdam/NL
  • 5 Radiumhospitalet, Oslo University Hospital, 424 - Oslo/NO
  • 6 Clinical Development, Cantargia AB, SE-22381 - Lund/SE
More

Resources

Abstract 4992

Background

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).

Methods

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).

Results

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.

Conclusions

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

NCT03267316.

Legal entity responsible for the study

Cantargia AB.

Funding

Cantargia AB.

Editorial Acknowledgement

Disclosure

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.

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