TY - JOUR
T1 - Xilonix, a novel true human antibody targeting the inflammatory cytokine interleukin-1 alpha, in non-small cell lung cancer
AU - Hong, David S.
AU - Janku, Filip
AU - Naing, Aung
AU - Falchook, Gerald S.
AU - Piha-Paul, Sarina
AU - Wheler, Jennifer J.
AU - Fu, Siqing
AU - Tsimberidou, Apostolia M.
AU - Stecher, Michael
AU - Mohanty, Prasant
AU - Simard, John
AU - Kurzrock, Razelle
N1 - Funding Information:
This study was funded by XBiotech USA, Inc.
Publisher Copyright:
© 2015 Springer Science+Business Media.
PY - 2015/6/22
Y1 - 2015/6/22
N2 - 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.
AB - 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.
KW - Checkpoint inhibitor
KW - EGFR inhibtor
KW - Inflammation
KW - Interleukin 1
KW - Interleukin 1 alpha
KW - Non small cell lung cancer
KW - Resistance
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U2 - 10.1007/s10637-015-0226-6
DO - 10.1007/s10637-015-0226-6
M3 - Article
C2 - 25822109
AN - SCOPUS:84937760589
SN - 0167-6997
VL - 33
SP - 621
EP - 631
JO - Investigational New Drugs
JF - Investigational New Drugs
IS - 3
ER -