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Xilonix, a novel true human antibody targeting the inflammatory cytokine interleukin-1 alpha, in non-small cell lung cancer

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Summary

Background Advanced non-small cell lung cancer (NSCLC) patients were treated as part of a Phase I dose escalation and expansion study evaluating a true human monoclonal antibody targeting IL-1α (Xilonix), which is intended to modulate the malignant phenotype—inhibiting tumor growth, spread and offering relief of symptoms. Methods Sixteen NSCLC patients were included. Patients failed a median of 4 chemotherapy regimens, including 10/16 failing anti-EGFR therapy. Disease progression was evaluated using a multi-modal approach: tumor response, patient reported outcomes (EORTC-QLQC30), and lean body mass (LBM). Patients received infusions every 2 or 3 weeks until progression, and were followed 24 months to assess survival. Results There were no infusion reactions, dose-limiting toxicities, or deaths due to therapy. Albeit not statistically significant, there was a trend in IL-6 (−2.6 ± 18.5 (0.1 [−2.8–2.4]), platelet counts (−11 ± 54 (−4[−36.0–1.0]), CRP (−3.3 ± 30.2 (0.4 [−10.7–1.8]) and LBM (1.0 ± 2.5 (0.4 [−0.5–2.6]). Self-reported outcomes revealed reductions in pain, fatigue and improvement in appetite. Median survival was 7.6 (IQR 4.4–11.5) months, stratification based on prior anti-EGFR therapy revealed a median survival of 9.4 months (IQR 7.6–12.5) for those pretreated (N = 10) versus a survival of 4.8 months (IQR 4.3–5.7) for those without (N = 6, logrank p = 0.187). Conclusion Xilonix was well tolerated, with gains in LBM and improvement in symptoms suggesting a clinically important response. Although not statistically significant, the survival outcomes observed for patients with and without prior anti-EGFR therapy raises intriguing questions about the potential synergy of IL-1α blockade and anti-EGFR therapy. Further study for this agent in NSCLC is warranted.

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Compliance with ethical standards

Funding

This study was funded by XBiotech USA, Inc.

Conflicts of interest

DSH reports grants from Xbiotech during the conduct of the study.

RK reports funding for research.

MS and PM are employees of XBiotech with stock options. JS is an employee of XBiotech with stock options, and patents related to anti-IL-1α therapy.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Authors and Affiliations

  1. Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), Division of Cancer Medicine, MD Anderson Cancer Center, Unit 455, P.O. Box 301402, Houston, TX, 77030, USA

    David S. Hong, Filip Janku, Aung Naing, Gerald S. Falchook, Sarina Piha-Paul, Jennifer J. Wheler, Siqing Fu & Apostolia M. Tsimberidou

  2. XBiotech USA, Austin, TX, USA

    Michael Stecher, Prasant Mohanty & John Simard

  3. UC San Diego Moores Cancer Center, La Jolla, CA, USA

    Razelle Kurzrock

Authors
  1. David S. Hong
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  2. Filip Janku
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  3. Aung Naing
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  4. Gerald S. Falchook
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  5. Sarina Piha-Paul
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Corresponding author

Correspondence to David S. Hong.

Additional information

One sentence summary

IL-1α blockade may help overcome resistance to anti-EGFR therapy by inhibiting the immunosuppressive effects of tumor-associated inflammation.

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Supplementary Materials and Methods S1

EORTC Questionnaire (DOC 39 kb)

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Hong, D.S., Janku, F., Naing, A. et al. Xilonix, a novel true human antibody targeting the inflammatory cytokine interleukin-1 alpha, in non-small cell lung cancer. Invest New Drugs 33, 621–631 (2015). https://doi.org/10.1007/s10637-015-0226-6

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  • DOI: https://doi.org/10.1007/s10637-015-0226-6

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