Xilonix, a novel true human antibody targeting the inflammatory cytokine interleukin-1 alpha, in non-small cell lung cancer. Invest New Drugs 2015 Jun;33(3):621-31
Date
03/31/2015Pubmed ID
25822109Pubmed Central ID
PMC4482235DOI
10.1007/s10637-015-0226-6Scopus ID
2-s2.0-84937760589 (requires institutional sign-in at Scopus site) 55 CitationsAbstract
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.
Author List
Hong DS, Janku F, Naing A, Falchook GS, Piha-Paul S, Wheler JJ, Fu S, Tsimberidou AM, Stecher M, Mohanty P, Simard J, Kurzrock RAuthor
Razelle Kurzrock MD Center Associate Director, Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdultAged
Aged, 80 and over
Antibodies
Antibodies, Monoclonal
Antibodies, Monoclonal, Humanized
Antineoplastic Agents
Body Weight
Carcinoma, Non-Small-Cell Lung
Disease-Free Survival
Energy Metabolism
ErbB Receptors
Female
Humans
Inflammation Mediators
Interleukin-1alpha
Kaplan-Meier Estimate
Lung Neoplasms
Male
Middle Aged
Quality of Life
Radionuclide Imaging
Treatment Outcome