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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04856176
Recruitment Status : Recruiting
First Posted : April 23, 2021
Last Update Posted : January 21, 2022
Sponsor:
Collaborator:
Partner Therapeutics, Inc.
Information provided by (Responsible Party):
Tufts Medical Center

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Advanced Lung Non-Small Cell Carcinoma Non-Small Cell Carcinoma of Lung, TNM Stage 4 Drug: Granulocyte-Macrophage Colony-Stimulating Factor Drug: Pembrolizumab Drug: pemetrexed Drug: Paclitaxel Drug: Carboplatin Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 83 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: This is a Phase II open-label, multi- center, single arm trial using a Simon two-stage optimal design.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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%
Actual Study Start Date : January 3, 2022
Estimated Primary Completion Date : May 2024
Estimated Study Completion Date : May 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

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
250ug/m2

Drug: Pembrolizumab
200mg every 3 weeks

Drug: pemetrexed
500mg/m2

Drug: Paclitaxel
200mg/m2

Drug: Carboplatin
AUC 5/6




Primary Outcome Measures :
  1. Progression free survival (PFS) [ Time Frame: 24 Months ]
    Progression is measured according to RECIST 1.1 criteria.

  2. Overall Survival (OS) [ Time Frame: 24 months ]
    Patient survival status throughout their participation in the study


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04856176


Contacts
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Contact: Lori Pai, MD 617-636-5000 ext 8148 lpai@tuftsmedicalcenter.org
Contact: Latoya Lashley, MPH 617-636-5000 ext 5409 llashley@tuftsmedicalcenter.org

Locations
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United States, Massachusetts
Tufts Medical Center Recruiting
Boston, Massachusetts, United States, 02111
Contact: Lori Pai, MD    617-636-5000 ext 8148    lpai@tuftsmedicalcenter.org   
Contact: Latoya Lashley, MPH    617-636-5000 ext 5409    llashley@tuftsmedicalcenter.org   
Sponsors and Collaborators
Tufts Medical Center
Partner Therapeutics, Inc.
Publications:
Nemunaitis, J., Schiller, H., Ross, H., et. al. A Phase 2 Randomized Study of GM-CSF Gene-Modified Autologous Tumor Cell Immunotherapy (CG8123) with and without Low-Dose Cyclophosphamide in Advanced Stage Non-Small Cell Lung Cancer (NSCLC). Molecular Therapy 2006; Volume 13, Supplement 1

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Responsible Party: Tufts Medical Center
ClinicalTrials.gov Identifier: NCT04856176    
Other Study ID Numbers: GM-CSF
First Posted: April 23, 2021    Key Record Dates
Last Update Posted: January 21, 2022
Last Verified: January 2022

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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
Additional relevant MeSH terms:
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Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Molgramostim
Sargramostim
Carcinoma
Carcinoma, Bronchogenic
Respiratory Tract Diseases
Paclitaxel
Carboplatin
Pembrolizumab
Pemetrexed
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological
Enzyme Inhibitors
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors
Immunologic Factors