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

Investigators are building an empirical evidence base for real-world data through large-scale emulation of randomized controlled trials. The investigators' goal is to understand for what types of clinical questions real-world data analyses can be conducted with confidence and how to implement such studies.

Study Overview

• Status: Active, not recruiting
• Conditions: Advanced Non-squamous Non-small-cell Lung Cancer; Advanced Squamous Non Small Cell Lung Cancer
• Intervention / Treatment: Drug: Initiation of nivolumab; Drug: Initiation of docetaxel

Detailed Description

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 Type: Observational
• Enrollment (Estimated): 810

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Somerville, Massachusetts, United States, 02145
      • Brigham and Women's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

Subjects with NSCLC who present with advanced/metastatic (Stage IIIB/ Stage IV) disease and have experienced disease recurrence or progression during or after the prior platinum doublet-based chemotherapy regimen

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Initiation of nivolumab; Exposure group	Drug: Initiation of nivolumab; Initiation of nivolumab described in electronic health records is used as the exposure.
Initiation of docetaxel; Reference group	Drug: Initiation of docetaxel; Initiation of docetaxel described in electronic health records is used as the reference.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival [OS] - Time to all-cause mortality	Hazard ratio (95% CI) for overall survival	Through the earliest of outcome, censoring, or end of data (April 2024)

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Collaborators: Food and Drug Administration (FDA)
• Investigators: Principal Investigator: Shirley Wang, PhD, ScM, Brigham and Women's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 12, 2026
• Primary Completion (Estimated): September 12, 2026
• Study Completion (Estimated): March 12, 2027

Study Registration Dates

• First Submitted: March 13, 2026
• First Submitted That Met QC Criteria: March 16, 2026
• First Posted (Actual): March 20, 2026

Study Record Updates

• Last Update Posted (Actual): May 8, 2026
• Last Update Submitted That Met QC Criteria: May 7, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Other Study ID Numbers: 2022P002556-ENC-CheckMate1757

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No