Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC)NCT07485179
Emulation of the KEYNOTE-042 (NCT02220894) Trial Using Specialty Oncology Electronic Health Records Databases
An observational study of Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC), run by Brigham and Women's Hospital at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC)
- What is being tested?
- Initiation of pembrolizumab and Initiation of chemotherapy
- Type of treatment
- Injection or infusion
- How many people
- 770 participants
- Where
- 1 siteUnited States
- Study dates
- 12 Mar 2026to 12 Mar 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Subjects with histologically or cytologically confirmed advanced or metastatic NSCLC that is not amenable to curative-intent treatment
Who may be able to join
- Age ≥18 years at treatment initiation
- Subjects with histologically or cytologically confirmed advanced or metastatic NSCLC that is not amenable to curative-intent treatment
- ECOG 0 or 1
- Line of therapy setting classified as "advanced" (EDB1) or "metastatic" (EDB2), or evidence of metastatic disease at treatment initiation (EDB4)
- PD-L1 ≥ 50%
Who cannot join
- Patients with documentation of prior chemotherapy administration for advanced/metastatic NSCLC
- Pembrolizumab group: patients with documented EGFR/ALK positivity
- Chemotherapy group: patients with documented EGFR/ALK positivity or missing/unknown EGFR/ALK status
- Missing/unknown or PD-L1 < 50%
- Patients with any documentation of an investigational agent within 4 weeks prior to initiation of first-line pembrolizumab/chemotherapy
- Squamous patients with any documentation of prior carboplatin plus paclitaxel
Show all 12Show fewer
- Patients with any documentation of chemotherapy or biologic therapy within 3 weeks prior to initiation of first-line pembrolizumab/chemotherapy
- Patients with documentation of prior immunotherapy administration
- Patients with any prior non-lung malignancy diagnosis (exceptions: basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, and in situ cervical cancer)
- Patients with documented autoimmune diseases within 2 years prior to treatment initiation
- Patients with documented interstitial lung disease
- Patients with documented CNS metastases
Trial locations and contacts
1 site in 1 country.
United States1 site
Brigham and Women's Hospital
Somerville, Massachusetts, 02145
About this study
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.
Read the 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-042.5 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. The trial had 3 co-primary analyses that focused on patients with PD-L1 TPS ≥50%, PD-L1 TPS ≥20%, and PD-L1 TPS ≥1%, respectively. The investigators will focus on the PD-L1 ≥50% subgroup as the primary analysis for this emulation because the vast majority of patients treated with pembrolizumab in clinical practice have PD-L1 ≥50%.
- Being tested
- Initiation of pembrolizumab, Initiation of chemotherapy
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Initiation of pembrolizumabDrug
Initiation of pembrolizumab (IV infusion) described in electronic health records is used as the exposure.
Initiation of chemotherapyDrug
Initiation of chemotherapy (carboplatin plus paclitaxel or pemetrexed for 4-6 cycles) described in electronic health records is used as the reference.
| Study group | Role | What they receive |
|---|---|---|
| Initiation of pembrolizumab | Exposure group Receives: Drug: Initiation of pembrolizumab | |
| Initiation of chemotherapy | Reference group Receives: Drug: Initiation of chemotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall survival [OS] - Time to all-cause mortality (OS)
Hazard ratio (95% CI) for overall survival
Measured: Time from the end of the treatment assessment window defined by the vendor's business rules to identify the line of therapy until the earliest of outcome, censoring, or end of data availability
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Mar 2026
- Study start12 Mar 2026
- Primary completion12 Mar 2027 (estimated)
- Study completion12 Mar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC)Studies of the same condition, open and under way.
- More trials run by Brigham and Women's HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 770 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Brigham and Women's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Food and Drug Administration (FDA)
- Responsible party
- Principal investigator, Shirley Vichy Wang, Brigham and Women's Hospital
- Investigators
- Shirley Wang, PhD, ScM, Principal investigator, Brigham and Women's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07485179
- Sponsor's protocol ID
- 2022P002556-ENC-KEYNOTE-042
- Status last verified
- Feb 2026
- First submitted
- 13 Mar 2026
- Last updated
- 15 Oct 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Emulation of the KEYNOTE-042 (NCT02220894) Trial Using Specialty Oncology Electronic Health Records Databases
- ClinicalTrials.gov ID
- NCT07485179
- Acronym / sponsor ID
- 2022P002556-ENC-KEYNOTE-042
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 770 participants (estimated)
- Lead sponsor
- Brigham and Women's HospitalUniversity, hospital or other
- Collaborators
- Food and Drug Administration (FDA)
- Study start
- 12 Mar 2026 (actual)
- Primary completion
- 12 Mar 2027 (estimated)
- Study completion
- 12 Mar 2027 (estimated)
- First posted
- 20 Mar 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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-042.5 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. The trial had 3 co-primary analyses that focused on patients with PD-L1 TPS ≥50%, PD-L1 TPS ≥20%, and PD-L1 TPS ≥1%, respectively. The investigators will focus on the PD-L1 ≥50% subgroup as the primary analysis for this emulation because the vast majority of patients treated with pembrolizumab in clinical practice have PD-L1 ≥50%.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Initiation of pembrolizumab | – | Drug: Initiation of pembrolizumabExposure group |
| Initiation of chemotherapy | – | Drug: Initiation of chemotherapyReference group |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Subjects with histologically or cytologically confirmed advanced or metastatic NSCLC that is not amenable to curative-intent treatment
Key inclusion criteria (5 listed)
- Age ≥18 years at treatment initiation
- Subjects with histologically or cytologically confirmed advanced or metastatic NSCLC that is not amenable to curative-intent treatment
- ECOG 0 or 1
- Line of therapy setting classified as "advanced" (EDB1) or "metastatic" (EDB2), or evidence of metastatic disease at treatment initiation (EDB4)
- PD-L1 ≥ 50%
Key exclusion criteria (12 listed)
- Patients with documentation of prior chemotherapy administration for advanced/metastatic NSCLC
- Pembrolizumab group: patients with documented EGFR/ALK positivity
- Chemotherapy group: patients with documented EGFR/ALK positivity or missing/unknown EGFR/ALK status
- Missing/unknown or PD-L1 < 50%
- Patients with any documentation of an investigational agent within 4 weeks prior to initiation of first-line pembrolizumab/chemotherapy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Initiation of pembrolizumabInitiation of pembrolizumab (IV infusion) described in electronic health records is used as the exposure. | Drug | Initiation of pembrolizumab |
| Initiation of chemotherapyInitiation of chemotherapy (carboplatin plus paclitaxel or pemetrexed for 4-6 cycles) described in electronic health records is used as the reference. | Drug | Initiation of chemotherapy |
Primary outcome
Overall survival [OS] - Time to all-cause mortality (OS)
Time frame: Time from the end of the treatment assessment window defined by the vendor's business rules to identify the line of therapy until the earliest of outcome, censoring, or end of data availability
Hazard ratio (95% CI) for overall survival
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Oct 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Shirley Wang, PhD, ScM principal investigator
Brigham and Women's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC), run by Brigham and Women's Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 15 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall survival [OS] - Time to all-cause mortality (OS) (time frame: Time from the end of the treatment assessment window defined by the vendor's business rules to identify the line of therapy until the earliest of outcome, censoring, or end of data availability). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Oct 2026.