CARE Initiative: Real-world Emulation of the KEYNOTE-189 Trial [DS3]

September 19, 2024 updated by: Aetion, Inc.

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:

  1. 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?
  2. How do the results of this non-interventional study compare to those of the KEYNOTE-189 randomized controlled trial?

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Observational

Enrollment (Actual)

851

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

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)

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • Histology indicative of squamous cell carcinoma or small cell elements
  • 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
  • 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 autoimmune disease and treatment with corticosteroids or immunosuppressive drugs after diagnosis and within the 2 years prior to study drug initiation
  • Treatment with a non-topical systemic steroid in each of the 6 months prior to study drug initiation
  • Prior treatment with pembrolizumab or any other anti-PD-1, PD-L1, PD-L2 agent or an antibody targeting other immuno-regulatory receptors or mechanisms
  • Treatment with non-topical antibiotics, antifungals, or antivirals within 2 weeks after an infection diagnosis in the month prior to study drug initiation
  • Diagnosis of human immunodeficiency virus infection
  • Diagnosis of acute hepatitis B or C
  • Diagnosis of ascites or plural effusion in the 3 months prior to study drug initiation
  • Prior diagnosis of interstitial lung disease or diagnosis of pneumonitis and record of treatment with glucocorticoids within 30 days

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Exposed
Patients initiating pemetrexed, cisplatin or carboplatin, and pembrolizumab as first-line treatment for metastatic NSCLC
Drug: Cisplatin
Drug: Pemetrexed
Drug: Pembrolizumab
Drug: Carboplatin
Comparator
Patients initiating pemetrexed and cisplatin or carboplatin as first-line treatment for metastatic NSCLC
Drug: Cisplatin
Drug: Pemetrexed
Drug: Carboplatin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Real-world overall survival (rwOS)
Time Frame: From study treatment initiation until the date of death from any cause or censoring, whichever came first, assessed up to 20.4 months.
Time from study treatment initiation to death
From study treatment initiation until the date of death from any cause or censoring, whichever came first, assessed up to 20.4 months.
Real-world progression-free survival (rwPFS)
Time Frame: From study treatment initiation until the date of disease progression, death from any cause or censoring, whichever came first, assessed up to 20.4 months.
Time from study treatment initiation to disease progression or death
From study treatment initiation until the date of disease progression, death from any cause or censoring, whichever came first, assessed up to 20.4 months.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Aetion, Inc.

Collaborators

Bayer
Pfizer
AbbVie
Gilead Sciences
AstraZeneca
Amgen
Janssen, LP

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 1, 2010

Primary Completion (Actual)

June 28, 2023

Study Completion (Actual)

June 28, 2023

Study Registration Dates

First Submitted

September 3, 2024

First Submitted That Met QC Criteria

September 19, 2024

First Posted (Actual)

September 23, 2024

Study Record Updates

Last Update Posted (Actual)

September 23, 2024

Last Update Submitted That Met QC Criteria

September 19, 2024

Last Verified

September 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DS3-KN189

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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