Emulation of the CheckMate 017/057 (NCT01642004 and NCT01673867) Trials Using Specialty Oncology Electronic Health Records Databases

Randomized controlled trials (RCTs) are generally regarded as the gold-standard of evidence for establishing efficacy of medical products. However, real-world data (RWD) are increasingly used to complement evidence from RCTs. Yet, to have confidence in the accuracy of non-interventional studies of medical products and their outcomes in oncology, investigators need to know what questions can be validly answered, with which non-interventional study designs, and which analysis methods are appropriate, given the data that is available. Building on a process from the RCT DUPLICATE initiative, EmulatioN of Comparative Oncology trials with Real-world Evidence (ENCORE) is the trial emulation discussed in this protocol is part of the expansion project specific to oncology and aims to emulate 12 randomized oncology RCTs using multiple EHR data sources.

The purpose of this protocol is to describe the emulation of the pooled analysis of CheckMate 017 and CheckMate 057. CheckMate 017/057 were two Phase III, double-blind, randomised studies assessing the efficacy and safety of Nivolumab (3 mg/kg IV every 2 weeks) versus Docetaxel (75 mg/m² IV every 3 weeks) in patients with squamous (CheckMate 017) and nonsquamous (CheckMate 057) advanced Non-small Cell Lung Cancer (NSCLC) and disease progression during or after prior platinum-based chemotherapy.

Study Period:

ENCORE database 1 (EDB1): Patient identification period: 01/01/2011-04/30/2024 with follow-up information through data cut-off date on 04/30/2024

ENCORE database 2 (EDB2): Follow-up information through February 2023 (there is no specific time period restrictions for patient eligibility)

ENCORE database 4 (EDB4): Patient identification period: 10/01/2018-09/30/2023 with follow-up information through data cut-off date on 09/30/2023.

Inclusion criteria

• Age ≥18 years at treatment initiation
• Line-of-therapy setting is "advanced" (EDB1), "metastatic" (EDB2), or evidence of metastatic disease at treatment initiation (EDB4)
• Subjects with NSCLC who present with advanced/metastatic (Stage IIIB/ Stage IV) disease and received treatment with nivolumab or docetaxel is 2L for advanced/metastatic diseases
• ECOG 0 or 1 in the 90 days before/on treatment initiation

Exclusion criteria

• Patients without documentation of disease progression between initiation of 1L platinum doublet-based chemotherapy and initiation of nivolumab or docetaxel
• Patients with documentation of docetaxel or nivolumab use before treatment initiation
• Patients with documentation of immunotherapy use before treatment initiation
• Patients with any prior non-lung malignancy diagnosis (except non-melanoma skin cancers and specified in situ cancers: bladder, gastric, colon, cervical/dysplasia, endometrial, melanoma, or breast)
• Patients with documented autoimmune diseases within 2 years before/on treatment initiation
• Patients with documented interstitial lung disease before/on treatment initiation
• Patients with documented CNS metastases before/on treatment initiation
• Patients with any other anti-cancer therapy during the treatment assessment window