NCT07485179

Emulation of the KEYNOTE-042 (NCT02220894) Trial Using Specialty Oncology Electronic Health Records Databases

• Status: Active Not Recruiting
• Phase: —
• Study type: Observational
• Enrollment: 770 (estimated)
• Sponsor: Brigham and Women's Hospital · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

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 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, which 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 KEYNOTE-042. KEYNOTE-042 was Phase III, double-blind, randomised study assessing the efficacy and safety of pembrolizumab monotherapy (200 mg intravenously every 3 weeks for up to 35 cycles) versus investigator's choice of platinum-based chemotherapy (carboplatin plus paclitaxel or pemetrexed for 4-6 cycles, with optional pemetrexed maintenance for non-squamous histology) in patients with previously untreated advanced or metastatic non-small-cell lung cancer (NSCLC) without sensitising EGFR mutations or ALK translocations, and whose tumours expressed programmed death-ligand 1 (PD-L1) with a tumour proportion score (TPS) of 1% or greater.

Conditions

• Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC)

Interventions

Type	Name	Description
DRUG	Initiation of pembrolizumab	Initiation of pembrolizumab (IV infusion) described in electronic health records is used as the exposure.
DRUG	Initiation of chemotherapy	Initiation of chemotherapy (carboplatin plus paclitaxel or pemetrexed for 4-6 cycles) described in electronic health records is used as the reference.

Timeline

• Start date: 2026-03-12
• Primary completion: 2026-09-12
• Completion: 2027-03-12
• First posted: 2026-03-20
• Last updated: 2026-03-20

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study