Metastatic Non Small Cell Lung CancerNCT06585189
CARE Initiative: Real-world Emulation of the KEYNOTE-189 Trial [DS4]
An observational study of Metastatic Non Small Cell Lung Cancer, run by Aetion, Inc..
Trial summary
The goal of this non-interventional study is to emulate the KEYNOTE-189 randomized controlled trial of pembrolizumab for the treatment of metastatic non-small cell lung cancer using real-world, electronic health record data. The main questions this study aims to answer are: 1. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Non Small Cell Lung Cancer
- What is being tested?
- Pembrolizumab, Pemetrexed and Cisplatin
- How many people
- 304 participants
- Where
- No sites listed yet
- Study dates
- 1 Feb 2010to 13 Apr 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
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: Patients identified in the electronic health record data source with metastatic EGFR/ALK-negative non-small cell lung cancer initiating treatment with the study drugs (pemetrexed, cisplatin/carboplatin, pembrolizumab)
Who may be able to join
- Non-small cell lung cancer (NSCLC) diagnosis
- Histology not indicative of squamous cell carcinoma
- Metastatic disease
- Epidermal growth factor receptor (EGFR) and Anaplastic lymphoma kinase (ALK)-negative or Kirsten rat sarcoma viral oncogene homolog (KRAS)-positive
- No prior systemic treatment for metastatic NSCLC
- No record of adjuvant or neoadjuvant therapy in the 12 months before metastatic diagnosis
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or missing or Karnofsky performance status >=70 or missing
- No lab results indicating inadequate organ function, as defined in the KEYNOTE-189 RCT protocol
Who cannot join
- Histology indicative of squamous cell carcinoma or small cell elements
- Receipt of an investigational agent or device in the 4 weeks before study drug initiation
- Prior systemic treatment for metastatic NSCLC
- Prior antineoplastic biological therapy
- History of major cancer-related surgery in the 3 weeks before study drug initiation
- Radiation therapy to the lung >30 Gy in the 6 months before study drug initiation
Show all 12Show fewer
- Prior diagnosis of clinically active diverticulitis, intra-abdominal abscess, or gastrointestinal obstruction
- Diagnosis of a second primary malignant neoplasm
- Diagnosis of brain, central nervous system, and/or spinal cord metastases
- Diagnosis of rheumatic disease in the 2 years prior to study drug initiation
- Prior treatment with pembrolizumab or any other anti-PD-1, PD-L1, PDL2 agent or an antibody targeting other immuno-regulatory receptors or mechanisms
- Diagnosis of human immunodeficiency virus infection
About this study
Official title: CARE Initiative Study: Real-world Emulation of the KEYNOTE-189 Comparative Effectiveness Trial of Pembrolizumab, Pemetrexed, and Chemotherapy vs. Placebo, Pemetrexed, and Chemotherapy for the First-line Treatment of Metastatic Non-small Cell Lung Cancer
The goal of this non-interventional study is to emulate the KEYNOTE-189 randomized controlled trial of pembrolizumab for the treatment of metastatic non-small cell lung cancer using real-world, electronic health record data. The main questions this study aims to answer are:
- Do patients with metastatic non-small cell lung cancer (NSCLC) treated with pemetrexed, cisplatin/carboplatin, and pembrolizumab have improved real-world overall survival (rwOS) and real-world progression-free survival (rwPFS) compared with patients treated with pemetrexed and cisplatin/carboplatin alone?
- How do the results of this non-interventional study compare to those of the KEYNOTE-189 randomized controlled trial?
Read the detailed description
The Coalition to Advance Real-World Evidence through Randomized Controlled Trial Emulation (CARE) Initiative is a program designed to build an empirical evidence base for the use of real-world data (RWD) in clinical and regulatory decision-making. Using randomized controlled trials (RCTs) as a benchmark for causal effect estimates, a series of RCT emulations will be conducted across varying trials, real world data sources, and study design elements to better understand under what conditions non-interventional studies, using data generated during routine clinical care, can provide reliable conclusions about drug effectiveness.
In this study, real-world electronic health record (EHR) data will be used to emulate the KEYNOTE-189 efficacy trial of pembrolizumab as first-line therapy in patients with metastatic non-small cell lung cancer (NSCLC) without epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) sensitizing mutations. Similarly to the KEYNOTE-189 trial, this study will compare real-world overall survival (rwOS) and real-world progression-free survival (rwPFS) between patients who initiate pemetrexed, platinum-based chemotherapy, and pembrolizumab, and patients who initiate pemetrexed and platinum-based chemotherapy alone.
- Conditions
- Metastatic Non Small Cell Lung Cancer
- Being tested
- Pembrolizumab, Pemetrexed, Cisplatin, Carboplatin
- Keywords
- real-world evidence, real-world data, oncology, pharmacoepidemiology, comparative effectiveness research, trial emulation
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabDrug
PemetrexedDrug
CisplatinDrug
CarboplatinDrug
| Study group | Role | What they receive |
|---|---|---|
| Exposed | Patients initiating pemetrexed, cisplatin or carboplatin, and pembrolizumab as first-line treatment for metastatic NSCLC Receives: Drug: Pembrolizumab; Drug: Pemetrexed; Drug: Cisplatin; Drug: Carboplatin | |
| Comparator | Patients initiating pemetrexed and cisplatin or carboplatin as first-line treatment for metastatic NSCLC Receives: Drug: Pemetrexed; Drug: Cisplatin; Drug: Carboplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Real-world overall survival (rwOS)
Time from study treatment initiation to death
Measured: Study treatment initiation to death or censoring
Real-world progression-free survival (rwPFS)
Time from study treatment initiation to disease progression or death
Measured: Study treatment initiation to disease progression, death, or censoring
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Sep 2024
- Study start1 Feb 2010
- Primary completion13 Apr 2023
- Study completion13 Apr 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Metastatic Non Small Cell Lung CancerStudies of the same condition, open and under way.
- 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
- 304 participants (actual)
Sponsor and investigators
- Lead sponsor
- Aetion, Inc.
- Sponsor type
- University, hospital or other
- Collaborators
- AbbVie, Amgen, AstraZeneca, Bayer, Gilead Sciences, Janssen, LP, Pfizer
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06585189
- Sponsor's protocol ID
- DS4-KN189
- Status last verified
- Sep 2024
- First submitted
- 3 Sep 2024
- Last updated
- 5 Sep 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Gandhi L, Rodriguez-Abreu D, Gadgeel S, Esteban E, Felip E, De Angelis F, Domine M, Clingan P, Hochmair MJ, Powell SF, Cheng SY, Bischoff HG, Peled N, Grossi F, Jennens RR, Reck M, Hui R, Garon EB, Boyer M, Rubio-Viqueira B, Novello S, Kurata T, Gray JE, Vida J, Wei Z, Yang J, Raftopoulos H, Pietanza MC, Garassino MC; KEYNOTE-189 Investigators. Pembrolizumab plus Chemotherapy in Metastatic Non-Small-Cell Lung Cancer. N Engl J Med. 2018 May 31;378(22):2078-2092. doi: 10.1056/NEJMoa1801005. Epub 2018 Apr 16.
PubMed 29658856
Study at a glance
From the registry record, last updated by the sponsor on 5 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- CARE Initiative Study: Real-world Emulation of the KEYNOTE-189 Comparative Effectiveness Trial of Pembrolizumab, Pemetrexed, and Chemotherapy vs. Placebo, Pemetrexed, and Chemotherapy for the First-line Treatment of Metastatic Non-small Cell Lung Cancer
- ClinicalTrials.gov ID
- NCT06585189
- Acronym / sponsor ID
- DS4-KN189
- Conditions
- Metastatic Non Small Cell Lung Cancer
- Keywords
- real-world evidence, real-world data, oncology, pharmacoepidemiology, comparative effectiveness research, trial emulation
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 304 participants (actual)
- Lead sponsor
- Aetion, Inc.University, hospital or other
- Collaborators
- AbbVie, Amgen, AstraZeneca, Bayer, Gilead Sciences, Janssen, LP, Pfizer
- Study start
- 1 Feb 2010 (actual)
- Primary completion
- 13 Apr 2023 (actual)
- Study completion
- 13 Apr 2023 (actual)
- First posted
- 5 Sep 2024 (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.
The goal of this non-interventional study is to emulate the KEYNOTE-189 randomized controlled trial of pembrolizumab for the treatment of metastatic non-small cell lung cancer using real-world, electronic health record data. The main questions this study aims to answer are:
- Do patients with metastatic non-small cell lung cancer (NSCLC) treated with pemetrexed, cisplatin/carboplatin, and pembrolizumab have improved real-world overall survival (rwOS) and real-world progression-free survival (rwPFS) compared with patients treated with pemetrexed and cisplatin/carboplatin alone?
- How do the results of this non-interventional study compare to those of the KEYNOTE-189 randomized controlled trial?
Detailed description
The Coalition to Advance Real-World Evidence through Randomized Controlled Trial Emulation (CARE) Initiative is a program designed to build an empirical evidence base for the use of real-world data (RWD) in clinical and regulatory decision-making. Using randomized controlled trials (RCTs) as a benchmark for causal effect estimates, a series of RCT emulations will be conducted across varying trials, real world data sources, and study design elements to better understand under what conditions non-interventional studies, using data generated during routine clinical care, can provide reliable conclusions about drug effectiveness.
In this study, real-world electronic health record (EHR) data will be used to emulate the KEYNOTE-189 efficacy trial of pembrolizumab as first-line therapy in patients with metastatic non-small cell lung cancer (NSCLC) without epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) sensitizing mutations. Similarly to the KEYNOTE-189 trial, this study will compare real-world overall survival (rwOS) and real-world progression-free survival (rwPFS) between patients who initiate pemetrexed, platinum-based chemotherapy, and pembrolizumab, and patients who initiate pemetrexed and platinum-based chemotherapy alone.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Exposed | – | Drug: Pembrolizumab, Drug: Pemetrexed, Drug: Cisplatin, Drug: CarboplatinPatients initiating pemetrexed, cisplatin or carboplatin, and pembrolizumab as first-line treatment for metastatic NSCLC |
| Comparator | – | Drug: Pemetrexed, Drug: Cisplatin, Drug: CarboplatinPatients initiating pemetrexed and cisplatin or carboplatin as first-line treatment for metastatic NSCLC |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients identified in the electronic health record data source with metastatic EGFR/ALK-negative non-small cell lung cancer initiating treatment with the study drugs (pemetrexed, cisplatin/carboplatin, pembrolizumab)
Key inclusion criteria (8 listed)
- Non-small cell lung cancer (NSCLC) diagnosis
- Histology not indicative of squamous cell carcinoma
- Metastatic disease
- Epidermal growth factor receptor (EGFR) and Anaplastic lymphoma kinase (ALK)-negative or Kirsten rat sarcoma viral oncogene homolog (KRAS)-positive
- No prior systemic treatment for metastatic NSCLC
Key exclusion criteria (12 listed)
- Histology indicative of squamous cell carcinoma or small cell elements
- Receipt of an investigational agent or device in the 4 weeks before study drug initiation
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 |
|---|---|---|
| Pembrolizumab | Drug | Exposed |
| Pemetrexed | Drug | Comparator, Exposed |
| Cisplatin | Drug | Comparator, Exposed |
| Carboplatin | Drug | Comparator, Exposed |
Primary outcome
Real-world overall survival (rwOS)
Time frame: Study treatment initiation to death or censoring
Time from study treatment initiation to death
Real-world progression-free survival (rwPFS)
Time frame: Study treatment initiation to disease progression, death, or censoring
Time from study treatment initiation to disease progression or death
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Sep 2024.
- Background: PubMed 29658856Gandhi L, Rodriguez-Abreu D, Gadgeel S, Esteban E, Felip E, De Angelis F, Domine M, Clingan P, Hochmair MJ, Powell SF, Cheng SY, Bischoff HG, Peled N, Grossi F, Jennens RR, Reck M, Hui R, Garon EB, Boyer M, Rubio-Viqueira B, Novello S, Kurata T, Gray JE, Vida J, Wei Z, Yang J, Raftopoulos H, Pietanza MC, Garassino MC; KEYNOTE-189 Investigators. Pembrolizumab plus Chemotherapy in Metastatic Non-Small-Cell Lung Cancer. N Engl J Med. 2018 May 31;378(22):2078-2092. doi: 10.1056/NEJMoa1801005. Epub 2018 Apr 16.
- Individual participant dataSharing planned: No
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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.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
An observational study of Metastatic Non Small Cell Lung Cancer, run by Aetion, Inc..
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 8 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: finished, as of the sponsor's last update on 5 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Real-world overall survival (rwOS) (time frame: Study treatment initiation to death or censoring). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06585189, which also lists 1 linked publication.
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 5 Sep 2024.