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A Multiple Antigen Vaccine (STEMVAC) for the Treatment of Patients With Stage IV Non-Small Cell Lung Cancer

ConditionsLung Non-Small Cell CarcinomaStage IV Lung Cancer AJCC v8
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorUniversity of Washington

About this trial

This phase II trial tests whether CD105/Yb-1/SOX2/CDH3/MDM2-polyepitope plasmid DNA vaccine (STEMVAC) works to shrink tumors in patients with stage IV non-small cell lung cancer. STEMVAC targets specific immunogenic proteins that help lung cancer cells to grow. STEMVAC is made up of deoxyribonucleic acid (DNA), which is a natural substance in every living organism. DNA acts like a blueprint that tells all the cells in your body how to function. The DNA used in this study contains instructions for your body to produce parts of the 5 proteins the investigators identified (CDH3, CD105, YB-1, MDM2 and SOX2). STEMVAC is given with granulocyte-macrophage colony stimulating factor (GM-CSF) which is being used as an adjuvant to help create a stronger immune response. Giving STEMVAC with GM-CSF to patients while on maintenance therapy for non-small cell lung cancer (NSCLC) may help activate certain immune cells to recognize and kill lung cancer cells.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Histologically-confirmed diagnosis of stage IV non-squamous or squamous NSCLC.

Have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 within one month of first vaccine. Target lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.

Have completed 3-4 cycles of chemoimmunotherapy, without evidence of progressive disease. Pembrolizumab has to be included in at least 3 of these cycles.

Have not received more than 2 cycles of maintenance pembrolizumab and/or pemetrexed and be a candidate for continuation of this therapy.

Disqualifiers

Symptomatic restrictive cardiomyopathy

Unstable angina within 4 months prior to enrollment

New York Heart Association functional class III-IV heart failure on active treatment

Symptomatic pericardial effusion

Trial design

Design model

Sequential

Treatments tested in this trial

  • CD105/Yb-1/SOX2/CDH3/MDM2-polyepitope Plasmid DNA Vaccine

    Biological/Vaccine

    Given ID

  • Sargramostim

    Biological/Vaccine

    Given ID

  • Computed Tomography

    Procedure/Surgery

    Undergo CT

  • Biopsy

    Procedure/Surgery

    Undergo biopsy

  • Biospecimen Collection

    Procedure/Surgery

    Undergo blood sample collection

Treatment groups

40 Participants
are divided into 2 treatment groups
Group A: Arm I (STEMVAC, sargramostim)Experimental treatment 5 interventions
Group B: Arm II (sargramostim)Active comparator 4 interventions

Trial outcomes

Primary outcomes

1

CD8 is Reported as a Fraction of CD3+ Tumor Infiltrating Lymphocytes (TIL) in 4 High-power Field (HPF)

Immunohistochemical (IHC) staining for CD8+ CD3+ will be performed on the biopsies collected pre-treatment and post 3rd vaccine administration.

Time frame
Baseline and after the third vaccine (at approximately 12 weeks)
2

Number of Participants With Recorded Adverse Event(s)

Will be evaluated using the modified National Cancer Institute (NCI) toxicity criteria. Toxicity evaluation will be based on Common Terminology Criteria for Adverse Events (CTCAE) v5.0

Time frame
Up to 20 weeks

Secondary outcomes

1

Magnitude of the Immune Response to CD105/Yb-1/SOX2/CDH3/MDM2-polyepitope Plasmid DNA Vaccine (STEMVAC)

Will measure the magnitude of the Th1 STEMVAC specific immune response using IFN-gamma enzyme-linked immunosorbent spot (ELISPOT). T-test among the 2 groups (vaccine and adjuvant alone) will be conducted to evaluate immune response if skewness is not observed.

Time frame
Up to 1 year
2

Vaccine Induced T-cells Traffic to Tumor

Will evaluate if vaccine induced T-cells traffic to tumor and eliminate cancer cells which have undergone epithelial to mesenchymal transformation (EMT). Will assess TCR-beta (TCRb) gene usage in both T-cell lines expanded from peripheral blood and in the tumor biopsy, and the expression of EMT related genes in the tumor after vaccination with STMEVAC+GM-CSF or GM-CSF alone. Shannon diversity index will be summarized and the Clopper-Pearson confidence interval will be computed for the rate of T-cell trafficking among the 10 patients subject to TCRb sequencing.

Time frame
Up to 1 year
3

Overall Response Rate (ORR)

Will evaluate potential clinical response approximately one month after the 3rd vaccine using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. An informal comparison will be conducted to compare the ORR between the two arms, with the Fisher exact test to account for small sample size.

Time frame
1 month after the 3rd vaccine (Up to 6 months)
4

Progression Free Survival (PFS)

Kaplan-Meier estimates of the survival function with 95% confidence intervals (CIs) at specific time points (using Greenwood's formula for the standard error) will be computed.

Time frame
Up to 5 years

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

University of Washington

Lead sponsor

United States Department of Defense

Collaborator

Source ClinicalTrials.gov
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