title: Xilonix, a novel true human antibody targeting the inflammatory cytokine interleukin-1 alpha, in non-small cell lung cancer.
abstract: 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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, dshong@mdanderson.org.
authors.forename: David S
authors.initials: DS
authors.lastname: Hong
authors.forename: Filip
authors.initials: F
authors.lastname: Janku
authors.forename: Aung
authors.initials: A
authors.lastname: Naing
authors.forename: Gerald S
authors.initials: GS
authors.lastname: Falchook
authors.forename: Sarina
authors.initials: S
authors.lastname: Piha-Paul
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Wheler
authors.forename: Siqing
authors.initials: S
authors.lastname: Fu
authors.forename: Apostolia M
authors.initials: AM
authors.lastname: Tsimberidou
authors.forename: Michael
authors.initials: M
authors.lastname: Stecher
authors.forename: Prasant
authors.initials: P
authors.lastname: Mohanty
authors.forename: John
authors.initials: J
authors.lastname: Simard
authors.forename: Razelle
authors.initials: R
authors.lastname: Kurzrock
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D001835:Body Weight / Q000187:drug effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging / Q000188:drug therapy*; D018572:Disease-Free Survival; D004734:Energy Metabolism / Q000187:drug effects; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D005260:Female; D006801:Humans; D018836:Inflammation Mediators; D053582:Interleukin-1alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D011877:Radionuclide Imaging; D016896:Treatment Outcome
chemical_list: D000906:Antibodies; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; C508584:IL1A protein, human; D018836:Inflammation Mediators; D053582:Interleukin-1alpha; D066246:ErbB Receptors; C000604877:bermekimab
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