A Study of Sargramostim Plus Pembrolizumab with or Without Pemetrexed in Patients with Advance Non-small Cell Lung Cancer After Completion of Chemoimmunotherapy

December 31, 2024 updated by: Tufts Medical Center

A Phase II Trial of GM-CSF Plus Maintenance Pembrolizumab +/- Pemetrexed After Completion of First Line Chemo-Immunotherapy in Advanced Non-Small Cell Lung Cancer Patients with PDL-1 of 1%-49%

Metastatic lung cancer is the leading cause of cancer mortality worldwide with a 5-year survival of less than 5%. With the approval of programmed cell death 1 (PD-1) inhibitors in advanced lung cancer, such as pembrolizumab, there has been an improvement in overall response rates (ORR) and survival compared to chemotherapy.

However, there is still a need for improvement in response rates in first-line treatments for patients with stage 4 NSCLC without genetically targetable alterations, especially in those patients with PDL-1 <50%.

This trial is important because it seeks to discover whether the responses seen in first line treatments with PD-1 inhibitors + chemotherapy can be augmented with the addition of GM-CSF during the maintenance phase with pembrolizumab +/- pemetrexed.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

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

Lung cancer is the most commonly diagnosed cancer worldwide. Metastatic lung cancer is the leading cause of cancer mortality worldwide with a 5-year survival of less than 5%. With the approval of programmed cell death 1 (PD-1) inhibitors in advanced lung cancer, there has been an improvement in overall response rates and survival compared to chemotherapy.

Checkpoint inhibition has become a primary treatment modality for vast number of cancers including lung cancer, prolonging survival in some patients. However, an important consideration is how to best select those patients who will respond to checkpoint inhibition. The biomarker that has been studied most extensively is PD-L1 expression. Studies have shown trends for increased response rates to PD-1 blockade in PD-L1 positive tumors.

NSCLC patients are now approved for pembrolizumab monotherapy (PDL-1>1%) or for pembrolizumab in combination with chemotherapy (carboplatin/pemetrexed for non-squamous or carboplatin/paclitaxel) (no minimum PDL-1). As the ORR and PFS in both these trials indicate, however, there is a need for improvement in response rates and PFS in first-line treatments for patients with stage 4 NSCLC without genetically targetable alterations especially in those patients with PDL-1 <50%.

There are both pre-clinical and clinical evidence supporting the combination of granulocyte macrophage colony stimulating factor (GM-CSF) with immunotherapy. GM-CSF is a hematopoietic growth factor that triggers proliferation and differentiation of hematopoietic progenitor cells, mainly neutrophils, monocytes/macrophages and myeloid-derived dendritic cells, and is approved by the FDA for this purpose.

A phase II randomized clinical trial of unresectable stage III or IV melanoma patients comparing the effects of ipilimumab plus GM-CSF vs ipilimumab alone was shown to be both safe and had longer overall survival with lower toxicity than immunotherapy alone; 1 year survival for ipilimumab plus sargramostim was 68.9% (95% CI, 60.6%-85.5%) compared to 52.9% (95% CI, 43.6%-62.2%) for ipilimumab alone.

It is hypothesized that the use of GM-CSF along with a PD-1 inhibitor +/- pemetrexed is safe and will increase the overall response rate and progression-free survival in advanced NSCLC patients with PDL-1 of 1%-49%. This will establish the basis for further evaluation of GM-CSF+PD-1 in advanced NSCLC patients.

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 (Actual)

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.
5

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

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02111
        • Tufts Medical Center

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

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. 18 years of age or older
  2. Histologically confirmed stage 4 NSCLC or stage 3B/3C not able to receive chemoradiation with no sensitizing EGFR or ALK mutations.
  3. PDL-1 of 1%-49%
  4. No previous history of immunotherapy treatment
  5. ECOG PS 0-1
  6. At least one measurable lesion according to RECIST version 1.1
  7. Life expectancy of at least 3 months.
  8. Able to self-administer daily GM-CSF injections
  9. Eligible for treatment with 4 cycles of chemoimmunotherapy followed by maintenance therapy with pembrolizumab +/- pemetrexed.

Exclusion Criteria:

  1. Receiving systemic glucocorticoids or other immunosuppressive treatment
  2. Untreated brain metastases
  3. Active autoimmune disease
  4. Active interstitial lung disease, pneumonitis
  5. Solid organ transplant recipients
  6. Subject may not participate in another drug research study while participating in this research study
  7. Pregnant patients
  8. Known hypersensitivity to GM-CSF (sargramostim)

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: GM-CSF Plus Maintenance Pembrolizumab +/- Pemetrexed
All patients will receive GM-CSF plus maintenance pembrolizumab with or without pemetrexed, following completion of 4 cycles of chemo-immunotherapy
Drug: Granulocyte-Macrophage Colony-Stimulating Factor
250 mcg
Drug: Pembrolizumab
200mg every 3 weeks
Drug: pemetrexed
500mg/m2
Drug: Paclitaxel
200mg/m2
Drug: Carboplatin
AUC 5/6

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 (PFS)
Time Frame: 24 Months
Progression is measured according to RECIST 1.1 criteria.
24 Months
Overall Survival (OS)
Time Frame: 24 months
Patient survival status throughout their participation in the study
24 months

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
To evaluate changes in monocytes at different time points during study treatment
Time Frame: 24 Months
Time points include study weeks 0, 12, 14 and 15
24 Months
To evaluate changes in myeloid derived suppressor cells at different time points during study treatment
Time Frame: 24 Months
Time points include study weeks 0, 12, 14 and 15
24 Months
To evaluate changes in CD4 T at different time points during study treatment
Time Frame: 24 Months
Time points include study weeks 0, 12, 14 and 15
24 Months
To evaluate changes in CD8 T at different time points during study treatment
Time Frame: 24 Months
Time points include study weeks 0, 12, 14 and 15
24 Months
To evaluate changes in PD-1+ CD4 at different time points during study treatment
Time Frame: 24 Months
Time points include study weeks 0, 12, 14 and 15
24 Months
To evaluate changes in PD-1+ CD8 at different time points during study treatment
Time Frame: 24 Months
Time points include study weeks 0, 12, 14 and 15
24 Months

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.
Tufts Medical Center

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Partner Therapeutics, Inc.

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)

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.
January 3, 2022

Primary Completion (Actual)

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.
December 6, 2024

Study Completion (Actual)

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.
December 6, 2024

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).
April 19, 2021

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.
April 19, 2021

First Posted (Actual)

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.
April 23, 2021

Study Record Updates

Last Update Posted (Actual)

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.
March 25, 2025

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.
December 31, 2024

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.
December 1, 2024

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.
  • GM-CSF

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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