TY - JOUR
T1 - Phase I/II Trial of Immunotherapy With Durvalumab and Tremelimumab With Continuous or Intermittent MEK Inhibitor Selumetinib in NSCLC
T2 - Early Trial Report
AU - Gaudreau, Pierre Olivier
AU - Lee, J. Jack
AU - Heymach, John V.
AU - Gibbons, Don L.
N1 - Funding Information:
Funding for this investigator-initiated trial is provided by AstraZeneca , with funding provided by the National Cancer Institute for correlative analyses of the tumor biopsies, R37CA214609 to D.L.G. P.-O.G. is supported by the Fonds de Recherche Québec-Santé ’s Resident Physician Health Research Career Training Program (32667).
Funding Information:
J.V. Heymach has received research support from AstraZeneca, Bayer, GlaxoSmithKline, and Spectrum; participated in advisory committees for AstraZeneca, Boehringer Ingelheim, Exelixis, Genentech, GlaxoSmithKline, Guardant Health, Hengrui, Lilly, Novartis, Specrtum, EMD Serono, and Synta; and received royalties and/or licensing fees from Spectrum. D.L. Gibbons has received research funding from AstraZeneca, Janssen, Ribon Therapeutics, and Takeda; and has participated in advisory boards for AstraZeneca and Sanofi.Funding for this investigator-initiated trial is provided by AstraZeneca, with funding provided by the National Cancer Institute for correlative analyses of the tumor biopsies, R37CA214609 to D.L.G. P.-O.G. is supported by the Fonds de Recherche Québec-Santé’s Resident Physician Health Research Career Training Program (32667).
Publisher Copyright:
© 2020 Elsevier Inc.
PY - 2020/7
Y1 - 2020/7
N2 - Current strategies to improve clinical outcomes in v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog-mutant non–small-cell lung cancer (NSCLC) patients include mitogen-activated protein kinase kinase 1 inhibitor and programmed death (PD) 1 (PD-1)/PD ligand 1 (PD-L1) immune checkpoint blockade combinations. Experience from treatment of melanoma suggests that anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and anti-PD-1/PD-L1 combinations improve outcomes, but similar benefits remain to be seen for treatment of NSCLC. This report describes a single center, investigator-initiated phase I/II clinical trial to compare 2 combination schedules of intermittent or continuous selumetinib (AZD6244, ARRY-142886), tremelimumab (anti-CTLA-4), and durvalumab (anti-PD-L1) treatment with historical controls in patients with previously treated, unresectable NSCLC. Forty patients will be accrued at the University of Texas M.D. Anderson Cancer Center. Primary objectives include maximum tolerated dose (dose escalation phase) and progression-free survival (dose expansion phase). Secondary objectives include response rate according to Response Evaluation Criteria In Solid Tumors version 1.1, disease control rate, overall survival, safety, and duration of response. Exploratory objectives are to assess biomarkers of response and resistance on the basis of biopsies and peripheral blood taken before and after treatment using immune profiling, transcriptome, and protein readouts.
AB - Current strategies to improve clinical outcomes in v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog-mutant non–small-cell lung cancer (NSCLC) patients include mitogen-activated protein kinase kinase 1 inhibitor and programmed death (PD) 1 (PD-1)/PD ligand 1 (PD-L1) immune checkpoint blockade combinations. Experience from treatment of melanoma suggests that anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and anti-PD-1/PD-L1 combinations improve outcomes, but similar benefits remain to be seen for treatment of NSCLC. This report describes a single center, investigator-initiated phase I/II clinical trial to compare 2 combination schedules of intermittent or continuous selumetinib (AZD6244, ARRY-142886), tremelimumab (anti-CTLA-4), and durvalumab (anti-PD-L1) treatment with historical controls in patients with previously treated, unresectable NSCLC. Forty patients will be accrued at the University of Texas M.D. Anderson Cancer Center. Primary objectives include maximum tolerated dose (dose escalation phase) and progression-free survival (dose expansion phase). Secondary objectives include response rate according to Response Evaluation Criteria In Solid Tumors version 1.1, disease control rate, overall survival, safety, and duration of response. Exploratory objectives are to assess biomarkers of response and resistance on the basis of biopsies and peripheral blood taken before and after treatment using immune profiling, transcriptome, and protein readouts.
KW - Anti-CTLA-4
KW - Anti-PD-L1
KW - Non–small-cell lung cancer
UR - http://www.scopus.com/inward/record.url?scp=85083089252&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85083089252&partnerID=8YFLogxK
U2 - 10.1016/j.cllc.2020.02.019
DO - 10.1016/j.cllc.2020.02.019
M3 - Article
C2 - 32299768
AN - SCOPUS:85083089252
SN - 1525-7304
VL - 21
SP - 384
EP - 388
JO - Clinical Lung Cancer
JF - Clinical Lung Cancer
IS - 4
ER -