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

November 21, 2023 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

Recruiting

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Estimated)

83

Phase

  • 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 Backup

Study Locations

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

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
Intervention / Treatment
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

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

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

Tufts Medical Center

Collaborators

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)

January 3, 2022

Primary Completion (Estimated)

December 1, 2024

Study Completion (Estimated)

December 1, 2024

Study Registration Dates

First Submitted

April 19, 2021

First Submitted That Met QC Criteria

April 19, 2021

First Posted (Actual)

April 23, 2021

Study Record Updates

Last Update Posted (Actual)

November 22, 2023

Last Update Submitted That Met QC Criteria

November 21, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID 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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