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Advanced Lung Non-Small Cell CarcinomaPhase 2NCT04856176

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

A Phase 2 study testing Granulocyte-Macrophage Colony-Stimulating Factor, Pembrolizumab and pemetrexed in people with Advanced Lung Non-Small Cell Carcinoma and Non-Small Cell Carcinoma of Lung, TNM Stage 4, run by Tufts Medical Center at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Granulocyte-Macrophage Colony-Stimulating Factor, Pembrolizumab and pemetrexed
Could I receive a placebo?
No, everyone receives an active treatment
How many people
5 participants
Where
1 siteUnited States
Study dates
3 Jan 2022to 6 Dec 2024
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

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

Who cannot join

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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Tufts Medical Center

    Boston, Massachusetts, 02111

Other trials in United States

About this study

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%

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.

Read the 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.

Being tested
Granulocyte-Macrophage Colony-Stimulating Factor, Pembrolizumab, pemetrexed, Paclitaxel, Carboplatin
Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT04856176
Study groupRoleWhat they receive
GM-CSF Plus Maintenance Pembrolizumab +/- PemetrexedExperimentalAll patients will receive GM-CSF plus maintenance pembrolizumab with or without pemetrexed, following completion of 4 cycles of chemo-immunotherapy
Receives: Drug: Granulocyte-Macrophage Colony-Stimulating Factor; Drug: Pembrolizumab; Drug: pemetrexed; Drug: Paclitaxel; Drug: Carboplatin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression free survival (PFS)

    Progression is measured according to RECIST 1.1 criteria.

    Measured: 24 Months

  2. Overall Survival (OS)

    Patient survival status throughout their participation in the study

    Measured: 24 months

Secondary outcomes (6)

  1. To evaluate changes in monocytes at different time points during study treatment

    Time points include study weeks 0, 12, 14 and 15

    Measured: 24 Months

  2. To evaluate changes in myeloid derived suppressor cells at different time points during study treatment

    Time points include study weeks 0, 12, 14 and 15

    Measured: 24 Months

  3. To evaluate changes in CD4 T at different time points during study treatment

    Time points include study weeks 0, 12, 14 and 15

    Measured: 24 Months

  4. To evaluate changes in CD8 T at different time points during study treatment

    Time points include study weeks 0, 12, 14 and 15

    Measured: 24 Months

  5. To evaluate changes in PD-1+ CD4 at different time points during study treatment

    Time points include study weeks 0, 12, 14 and 15

    Measured: 24 Months

  6. To evaluate changes in PD-1+ CD8 at different time points during study treatment

    Time points include study weeks 0, 12, 14 and 15

    Measured: 24 Months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Apr 2021
  2. Study start3 Jan 2022
  3. Primary completion6 Dec 2024
  4. Study completion6 Dec 2024

Why it stopped: Futility

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
This is a Phase II open-label, single-center, single arm trial using a Simon two-stage optimal design.
Masking
None (open label)
Enrolment
5 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04856176
Sponsor's protocol ID
GM-CSF
Status last verified
Oct 2026
First submitted
19 Apr 2021
Last updated
30 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Reck M, Rodriguez-Abreu D, Robinson AG, Hui R, Csoszi T, Fulop A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Leiby MA, Lubiniecki GM, Shentu Y, Rangwala R, Brahmer JR; KEYNOTE-024 Investigators. Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. N Engl J Med. 2016 Nov 10;375(19):1823-1833. doi: 10.1056/NEJMoa1606774. Epub 2016 Oct 8.

    PubMed 27718847

  • Gandhi L, Rodriguez-Abreu D, Gadgeel S, Esteban E, Felip E, De Angelis F, Domine M, Clingan P, Hochmair MJ, Powell SF, Cheng SY, Bischoff HG, Peled N, Grossi F, Jennens RR, Reck M, Hui R, Garon EB, Boyer M, Rubio-Viqueira B, Novello S, Kurata T, Gray JE, Vida J, Wei Z, Yang J, Raftopoulos H, Pietanza MC, Garassino MC; KEYNOTE-189 Investigators. Pembrolizumab plus Chemotherapy in Metastatic Non-Small-Cell Lung Cancer. N Engl J Med. 2018 May 31;378(22):2078-2092. doi: 10.1056/NEJMoa1801005. Epub 2018 Apr 16.

    PubMed 29658856

  • Paz-Ares L, Luft A, Vicente D, Tafreshi A, Gumus M, Mazieres J, Hermes B, Cay Senler F, Csoszi T, Fulop A, Rodriguez-Cid J, Wilson J, Sugawara S, Kato T, Lee KH, Cheng Y, Novello S, Halmos B, Li X, Lubiniecki GM, Piperdi B, Kowalski DM; KEYNOTE-407 Investigators. Pembrolizumab plus Chemotherapy for Squamous Non-Small-Cell Lung Cancer. N Engl J Med. 2018 Nov 22;379(21):2040-2051. doi: 10.1056/NEJMoa1810865. Epub 2018 Sep 25.

    PubMed 30280635

  • Shi X, Zhang X, Li J, Mo L, Zhao H, Zhu Y, Hu Z, Gao J, Tan W. PD-1 blockade enhances the antitumor efficacy of GM-CSF surface-modified bladder cancer stem cells vaccine. Int J Cancer. 2018 May 15;142(10):2106-2117. doi: 10.1002/ijc.31219. Epub 2017 Dec 26.

    PubMed 29243219

  • Hodi FS, Butler M, Oble DA, Seiden MV, Haluska FG, Kruse A, Macrae S, Nelson M, Canning C, Lowy I, Korman A, Lautz D, Russell S, Jaklitsch MT, Ramaiya N, Chen TC, Neuberg D, Allison JP, Mihm MC, Dranoff G. Immunologic and clinical effects of antibody blockade of cytotoxic T lymphocyte-associated antigen 4 in previously vaccinated cancer patients. Proc Natl Acad Sci U S A. 2008 Feb 26;105(8):3005-10. doi: 10.1073/pnas.0712237105. Epub 2008 Feb 19.

    PubMed 18287062

  • Fong L, Kwek SS, O'Brien S, Kavanagh B, McNeel DG, Weinberg V, Lin AM, Rosenberg J, Ryan CJ, Rini BI, Small EJ. Potentiating endogenous antitumor immunity to prostate cancer through combination immunotherapy with CTLA4 blockade and GM-CSF. Cancer Res. 2009 Jan 15;69(2):609-15. doi: 10.1158/0008-5472.CAN-08-3529.

    PubMed 19147575

  • 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

  • Hodi FS, Lee S, McDermott DF, Rao UN, Butterfield LH, Tarhini AA, Leming P, Puzanov I, Shin D, Kirkwood JM. Ipilimumab plus sargramostim vs ipilimumab alone for treatment of metastatic melanoma: a randomized clinical trial. JAMA. 2014 Nov 5;312(17):1744-53. doi: 10.1001/jama.2014.13943.

    PubMed 25369488

  • Simon R. Optimal two-stage designs for phase II clinical trials. Control Clin Trials. 1989 Mar;10(1):1-10. doi: 10.1016/0197-2456(89)90015-9.

    PubMed 2702835

  • Kwek SS, Kahn J, Greaney SK, Lewis J, Cha E, Zhang L, Weber RW, Leonard L, Markovic SN, Fong L, Spitler LE. GM-CSF and ipilimumab therapy in metastatic melanoma: Clinical outcomes and immunologic responses. Oncoimmunology. 2015 Oct 29;5(4):e1101204. doi: 10.1080/2162402X.2015.1101204. eCollection 2016 Apr.

    PubMed 27141383

  • Ohradanova-Repic A, Machacek C, Fischer MB, Stockinger H. Differentiation of human monocytes and derived subsets of macrophages and dendritic cells by the HLDA10 monoclonal antibody panel. Clin Transl Immunology. 2016 Jan 8;5(1):e55. doi: 10.1038/cti.2015.39. eCollection 2016 Jan.

    PubMed 26900469

  • Soiffer R, Lynch T, Mihm M, Jung K, Rhuda C, Schmollinger JC, Hodi FS, Liebster L, Lam P, Mentzer S, Singer S, Tanabe KK, Cosimi AB, Duda R, Sober A, Bhan A, Daley J, Neuberg D, Parry G, Rokovich J, Richards L, Drayer J, Berns A, Clift S, Cohen LK, Mulligan RC, Dranoff G. Vaccination with irradiated autologous melanoma cells engineered to secrete human granulocyte-macrophage colony-stimulating factor generates potent antitumor immunity in patients with metastatic melanoma. Proc Natl Acad Sci U S A. 1998 Oct 27;95(22):13141-6. doi: 10.1073/pnas.95.22.13141.

    PubMed 9789055

  • Scagliotti GV, Parikh P, von Pawel J, Biesma B, Vansteenkiste J, Manegold C, Serwatowski P, Gatzemeier U, Digumarti R, Zukin M, Lee JS, Mellemgaard A, Park K, Patil S, Rolski J, Goksel T, de Marinis F, Simms L, Sugarman KP, Gandara D. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. J Clin Oncol. 2008 Jul 20;26(21):3543-51. doi: 10.1200/JCO.2007.15.0375. Epub 2008 May 27.

    PubMed 18506025

  • Kaplan D, Sun Z, Tallman MS, Flinn IW, Xiao W, Caimi PF, Kaye NM, Lazarus HM. Prognostic information and biological insights in chronic lymphocytic leukemia by high-resolution immunophenotypic analysis of ZAP70. Cytometry A. 2014 Sep;85(9):798-808. doi: 10.1002/cyto.a.22485. Epub 2014 May 20.

    PubMed 24845539

  • Kaplan D, Smith D. Enzymatic amplification staining for flow cytometric analysis of cell surface molecules. Cytometry. 2000 May 1;40(1):81-5. doi: 10.1002/(sici)1097-0320(20000501)40:13.0.co;2-k.

    PubMed 10754521

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Granulocyte-Macrophage Colony-Stimulating Factor, Pembrolizumab and pemetrexed in people with Advanced Lung Non-Small Cell Carcinoma and Non-Small Cell Carcinoma of Lung, TNM Stage 4, run by Tufts Medical Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 30 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Futility). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression free survival (PFS) (time frame: 24 Months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04856176, which also lists 17 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Oct 2026.

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