A Phase III Study of Durvalumab (MEDI4736) With or Without Tremelimumab for Previously Treated Patients With Advanced NSCLC: Rationale and Protocol Design of the ARCTIC Study.
Anti-programmed cell death-1 and anti-programmed cell death ligand-1 (PD-L1) monotherapies have shown promising clinical activity in advanced, refractory non-small-cell lung cancer (NSCLC), but antitumor activity appears to be greater in patients with PD-L1(+) tumors compared with patients harboring PD-L1(-) tumors. Combining the anti-PD-L1 antibody durvalumab and the anti-cytotoxic T-lymphocyte antigen 4 antibody tremelimumab offers the potential for antitumor activity in patients with advanced NSCLC, regardless of PD-L1 tumor status. ARCTIC (NCT02352948) is a global, phase III, randomized, open-label multicenter study in patients with advanced NSCLC assessing the safety and clinical activity of durvalumab versus standard of care (SoC; erlotinib, gemcitabine, or vinorelbine) in patients with PD-L1(+) tumors (≥25% of tumor cells with membrane staining using VENTANA PD-L1 [SP263] CDx Assay) (Sub-study A) and the combination of durvalumab + tremelimumab or either agent as monotherapy versus SoC in patients with PD-L1(-) tumors (Sub-study B). Eligible patients are those with locally advanced or metastatic NSCLC (Stage IIIB/IV), without epidermal growth factor receptor tyrosine kinase activating mutations or anaplastic lymphoma kinase rearrangements, who have received at least 2 prior systemic regimens, including 1 platinum-based chemotherapy regimen. Co-primary endpoints are progression-free survival and overall survival. Secondary endpoints include the proportion of patients alive at 12 months, objective response rate, duration of response, progression-free survival at 6 and 12 months, safety and tolerability, pharmacokinetics, immunogenicity, and quality of life. The exploratory endpoints will assess potential biomarkers of treatment response. Recruitment started in January 2015 and is ongoing.
Department of Medical Oncology, Gustave Roussy, Villejuif, France. Electronic address: David.PLANCHARD@gustaveroussy.fr.
David
D
Planchard
First Department of Internal Medicine, Kansai Medical University, Osaka, Japan.
Takashi
T
Yokoi
Florida Cancer Specialists and Research Institute, Fort Myers, FL.
Michael J
MJ
McCleod
Department of Internal Medicine II, Lungenklinik Löwenstein GmbH, Löwenstein, Germany.
Jürgen R
JR
Fischer
Department of Internal Medicine, Chonnam National University Medical School, Hwasun Hospital, Hwasun, Jeonnam, South Korea.
Young-Chul
YC
Kim
Global Medical Development (GMD), AstraZeneca, Gaithersburg, MD.
Marc
M
Ballas
Biometrics and Information Sciences, AstraZeneca, Gaithersburg, MD.
Kelvin
K
Shi
DITEP (Département d'Innovations Thérapeutiques et Essais Précoces), Gustave Roussy, Villejuif, France.
Jean-Charles
JC
Soria
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D060890:B7-H1 Antigen / Q000276:immunology; D060908:CTLA-4 Antigen / Q000037:antagonists & inhibitors; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D004358:Drug Therapy; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D017671:Platinum Compounds / Q000627:therapeutic use; D012107:Research Design; D016019:Survival Analysis; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D060890:B7-H1 Antigen; D060908:CTLA-4 Antigen; D017671:Platinum Compounds; C000613593:durvalumab; C520704:tremelimumab
ALK; Anti-CTLA-4; Anti-PD-L1; EGFR; Tumor membrane staining