A Prospective Study of Pembrolizumab Combining Chemotherapy in Advanced NSCLC Patients With EGFR Exon 21 Point Mutation.

November 16, 2023 updated by: Peking Union Medical College Hospital

A Phase II Study of Pembrolizumab Plus Platinum and Pemetrexed as First Line Therapy in Advanced Non-squamous Non-small Cell Lung Cancer Patients With EGFR Exon 21 Point Mutation and Programmed Cell Death Ligand 1 Expression

A phase II, single-arm, open-label study evaluating efficacy, safety and feasibility of combined chemotherapy and pembrolizumab as first line therapy and Osimertinib as second line therapy in advanced non squamous NSCLC adult patients with epidermal growth factor receptor (EGFR) exon 21 point mutation and programmed cell death receptor ligand 1 (PD-L1) positive.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Four cycles of platinum and pemetrexed in combination with pembrolizumab will be administered as first line therapy and up to 31 cycles pemetrexed and pembrolizumab maintenance therapy every 3 weeks. Osimertinib will be the sequential treatment strategy at progression.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
37

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • China
      • Peking, China
        • Peking Union Medical College Hospital
        • Contact:

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Male or female, ≥18 years old
  2. Primary non-squamous non-small cell lung cancer(NSCLC) with stage IV (AJCC stage,8th Edition) confirmed by cytology or histology
  3. Patients who have not used any anti-tumor therapy drugs such as targeted drugs, chemotherapy or immunotherapy and patients after surgery are acceptable
  4. EGFR exon 21 point mutation confirmed by gene test of tissue or blood and PD-L1 (22C3) TPS≥1% confirmed by immunohistochemical method
  5. At least one evaluable focus judged according to RECIST 1.1 standard
  6. Eastern Cooperative Oncology Group performance score (PS) 0 or 1
  7. Adequate blood function: absolute neutrophil count (ANC) ≥ 2 × 109 / L, platelet count ≥ 100 × 109 / L and hemoglobin 110 ≥ 9 g / dl. Adequate renal function: serum creatinine ≤ upper limit of normal value. Adequate liver function: total bilirubin ≤ upper limit of normal value(ULN); Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ upper limit of normal value (ULN); alkaline phosphatase ≤ upper limit of normal value (ULN)
  8. Life expectancy is not less than 6 months
  9. Male participants: Male participants must take effective contraception and do not donate sperm during the study and 180 days at least after the last dose

  10. Female participants can not be pregnant, breastfeeding, and meet at least one of the following conditions:

    1. non-fertile women or
    2. agree to use effective contraception during treatment and 180 days at least after the last dose
    3. Fertile women must perform a serum or urine pregnancy test within 72 hours before the first dose and the results must be negative (minimum sensitivity 25 IU/L or human chorionic gonadotropin (HCG) equivalent unit)
  11. Sign the informed consent form (the informed consent form needs to be approved by the independent ethics committee, and the informed consent of the patient should be obtained before starting any substantive trial procedure)

Exclusion Criteria:

  1. patients who have active autoimmune disease which needs systemic treatment like disease relievers, corticosteroids, or immunosuppressants) in the last 2 years e. Alternative therapies ( such as thyroxine, insulin, and physiologic corticosteroid replacement therapy of adrenal or pituitary function insufficiency) are permitted)
  2. History of pneumonia (non-infectious)/interstitial lung disease which require s steroid treatment or a current pneumonia/interstitial lung disease
  3. Previously diagnosed immunodeficiency diseases, such as immunoglobulin deficiency, aplastic anemia
  4. Known history of human immunodeficiency virus (HIV) infection
  5. Patients who have hepatitis B (defined as hepatitis B virus (HBV) DNA > 1000 copy number) and hepatitis C virus (HCV) (defined as HCV RNA (+) infection
  6. Known history of active tuberculosis infection
  7. Patients who received live or attenuated vaccine within 30 days prior to the first study intervention and inactivated vaccines are allowed.
  8. Patients who have other known malignancies within the past 1 year and needs treatment. Basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ that has undergone potentially curative treatment, and bladder carcinoma in situ are not included.
  9. Patients who have symptomatic central nervous system metastases and/or meningitis
  10. History of hypersensitivity ( ≥ Level 3) to pembrolizumab/pemetrexed/platinum/osimertinib and/or any of its excipients
  11. Active infection that requires systemic treatment
  12. Any medical condition that the investigator believes might do harm to the patient or not in the best interest of the patients such as poorly controlled diabetes, infection requiring treatment by injection, liver failure, mental illness or any disease, treatment, laboratory abnormality that might confuse the results or interfere with the participation of patients throughout the study.
  13. Patients with mental illness or substance abuse which are confirmed to interfere with compliance with test requirements
  14. Planed or currently pregnant or lactation during the study (from beginning of the screening visit to 180 days after the last dose of the experimental drug)
  15. Patients who have undergone allogeneic tissue/solid organ transplantation
  16. Patients who could not accept regular follow-up
  17. Patients who are participating in or have used other investigational drugs or investigational equipment

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

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: experimental group
Four cycles of platinum and pemetrexed in combination with pembrolizumab will be administered as first line therapy and up to 31 cycles pemetrexed and pembrolizumab maintenance therapy every 3 weeks. Osimertinib will be the sequential treatment strategy at progression until resistance develops.
Drug: Pembrolizumab, pemetrexed, platinum
Four cycles of platinum and pemetrexed in combination with pembrolizumab will be administered as first line therapy and up to 31 cycles pemetrexed and pembrolizumab maintenance therapy every 3 weeks.
Other Names:
  • Keytruda, pemetrexed, platinum
Drug: Osimertinib
Osimertinib will be the sequential treatment strategy at progression until resistance develops.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
progression free survival 1 (PFS1)
Time Frame: up to 8 weeks
the time length from enrollment to any of the following events: disease progression with first line therapy or death from any cause. Disease progression will be assessed according to RECIST 1.1
up to 8 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
progression free survival 2 (PFS2)
Time Frame: up to 8weeks
the time length from enrollment to any of the following events: disease progression with Osimertinib or death from any cause. Disease progression will be assessed according to RECIST 1.1
up to 8weeks
Incidence of adverse events graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
Time Frame: up to 8 weeks
Evaluate adverse events of any cause, treatment-related adverse events, immune-mediated adverse events according to NCI-CTCAE V5.0
up to 8 weeks
objective response rate (ORR)
Time Frame: up to 8 weeks
Proportion of patients with Complete and Partial Responses to first-line therapy.
up to 8 weeks
Life quality score
Time Frame: up to 8 weeks
Evaluate life quality score according to Karnofsky performance status (KPS). On a scale of 10, higher scores indicate better health. A score of 0 is defined as death, on a 100-point scale, indicating normal physical fitness with no obvious symptoms and signs.
up to 8 weeks

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Exploratory biomarker analysis
Time Frame: before treatment, at the time of disease progression on first-line therapy, and at the time of disease progression on second-line therapy.
Blood samples will be collected from patients on three occasions: before treatment, at the time of disease progression on first-line therapy, and at the time of disease progression on second-line therapy. 15ml blood samples will be collected each time for PBMC assay. Tumor samples will be collected: 10 formalin-fixed, paraffin-embedded sections. Tumor samples will be subjected to genetic testing. Blood samples will be analyzed by flow cytometry.
before treatment, at the time of disease progression on first-line therapy, and at the time of disease progression on second-line therapy.

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Peking Union Medical College Hospital

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Mengzhao Wang, MD, Peking Union Medical College Hospital

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 (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 1, 2023

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 30, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 30, 2028

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 29, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 16, 2023

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 21, 2023

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 21, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 16, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • K4510

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

The result of the study and all the supporting information will be shared in the form of publishing article.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

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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