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

NCT05242965 | Active Not Recruiting Phase 2 DMC FDA Drug

• 4 other identifiers: RG1013946NCI-2021-1415910726W81XWH2110271
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Lung Non-Small Cell Carcinoma; Stage IV Lung Cancer AJCC v8

Outcome Measures

Primary Outcomes (2)

• Change from baseline percentage of CD8+ TIL in patients between the two arms

  Immunohistochemical (IHC) staining for CD3, CD4, and CD8 will be performed on the biopsies collected pre-treatment and post 3 vaccine administration. Two-sample Student's t-test with a 1-sided 0.05 significance level will be used to assess the difference. The distribution of the differences of CD8 T-cells between baseline and post treatment will be examined to check the normality assumption and outliers. If the outliers are substantial or the distribution is skewed, Wilcoxon nonparametric test will be used to assess the difference between the two treatment arms. Depending on the correlation between baseline and post-treatment measures, alternative analytical method will be adopted using an ordinary least square regression for the post-treatment CD8 T-cells percentage while adjusting for the baseline measure.

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

• Incidence of adverse events

  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

  Up to 1 year

Secondary Outcomes (6)

• Magnitude of the immune response to CD105/Yb-1/SOX2/CDH3/MDM2-polyepitope Plasmid DNA Vaccine (STEMVAC)

  Up to 1 year

• Vaccine induced T-cells traffic to tumor

  Up to 1 year

• Overall response rate (ORR)

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

• Progression free survival (PFS)

  Up to 5 years

• Overall survival (OS)

  Up to 5 years

Study Arms (2)

Arm I (STEMVAC, sargramostim)

EXPERIMENTAL

Patients receive STEMVAC ID and sargramostim ID on day 14 (+3 days) of the 21-day maintenance therapy cycle for a series of 3 vaccine doses and a booster vaccine 9 weeks after the third vaccine dose. Patients also undergo CT and biopsy during screening and on the trial, as well as blood sample collection on trial and during follow-up.

Biological: CD105/Yb-1/SOX2/CDH3/MDM2-polyepitope Plasmid DNA Vaccine; Biological: Sargramostim; Procedure: Computed Tomography; Procedure: Biopsy; Procedure: Biospecimen Collection

Arm II (sargramostim)

ACTIVE COMPARATOR

Patients receive sargramostim ID on day 14 (+3 days) of the 21-day maintenance therapy cycle for a series of 3 vaccine doses and a booster vaccine 9 weeks after the third vaccine dose. Patients also undergo CT and biopsy during screening and on the trial, as well as blood sample collection on trial and during follow-up.

Biological: Sargramostim; Procedure: Computed Tomography; Procedure: Biopsy; Procedure: Biospecimen Collection

Interventions

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

Given ID

Also known as: CD105/Yb-1/SOX2/CDH3/MDM2 Plasmid Vaccine, STEMVAC, STEMVAC Th1 Polyepitope Plasmid-based Vaccine

Arm I (STEMVAC, sargramostim)

Sargramostim BIOLOGICAL

Given ID

Also known as: 23-L-Leucinecolony-Stimulating Factor 2, DRG-0012, Leukine, Prokine, rhu GM-CFS, Sagramostim, Sargramostatin

Arm I (STEMVAC, sargramostim); Arm II (sargramostim)

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT Scan, Computed Axial Tomography, CT Scan

Arm I (STEMVAC, sargramostim); Arm II (sargramostim)

Biopsy PROCEDURE

Undergo biopsy

Also known as: Bx

Arm I (STEMVAC, sargramostim); Arm II (sargramostim)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection

Arm I (STEMVAC, sargramostim); Arm II (sargramostim)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• At least 1 site of disease that could be biopsied during treatment. This site should not be a site that is used to determine measurable disease for efficacy purposes. Lesions that will be biopsied should not be on a previously irradiated area unless progression has been demonstrated in such lesions.
• Patients must be at least 28 days post systemic steroids prior to enrollment, unless this is a steroid administered concurrently with chemotherapy or used as part of prophylaxis to prevent intravenous (IV) contrast reactions.
• Patients must have Eastern Cooperative Oncology Group (ECOG) Performance Status Score of 0 or 1.
• Patients must have recovered from major infections and/or surgical procedures, and in the opinion of a principle investigator (PI)/co-PI/study physician/physician extender, not have any significant active concurrent medical illnesses precluding protocol treatment.
• Willing to undergo up to two serial biopsies while on study.
• Estimated life expectancy of more than 6 months.
• White blood cells (WBC) \>= 3000/mm\^3 (within 60 days of first vaccination).
• Lymphocyte count \>= 800/mm\^3 (within 60 days of first vaccination).
• Platelet count \>= 75,000/mm\^3 (within 60 days of first vaccination).
• Hemoglobin (Hgb) \>= 9 g/dl (within 60 days of first vaccination).
• Serum creatinine =\< 1.2 mg/dl or creatinine clearance \> 50 ml/min (within 60 days of first vaccination).

You may not qualify if:

• Patients with any of the following cardiac conditions:
• 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
• Patients with central nervous system (CNS) metastasis that have not been treated. Patients with previously treated brain metastases may participate provided they are clinically stable for at least 4 weeks and, have no evidence of new or enlarging brain metastases and also are off steroids for 2 weeks prior to dosing with study medication.
• Patients with any contraindication to receiving recombinant human granulocyte-macrophage colony stimulating factor (rhuGM-CSF) based products.
• Patients with any clinically significant autoimmune disease that requires active treatment with immunosuppressants. Replacement therapy (e.g., thyroxine, insulin) is not considered a form of systemic treatment. Administration of systemic steroids (i.e., for allergic reactions, computed tomography (CT) scans, or the management of immune related adverse events \[irAEs\]) is allowed.
• Has a known history of another prior invasive malignancy within 2 years, except subjects with early stage cancer that has undergone potentially curative therapy with no evidence of that disease recurrence for 2 years since initiation of that therapy.
• Patients who are simultaneously enrolled in any other treatment study.
• Patients who are pregnant or breastfeeding.
• Patients with genetic driver alterations (e.g EGFR, ALK, ROS1, BRAF, MET ex 14, RET) for which targeted treatment exist and are Food and Drug Association (FDA) approved, except if the subject is not eligible or has progressed through those therapies.

Sponsors & Collaborators

• University of Washington: lead
• United States Department of Defense: collaborator

Study Sites (2)

VA Puget Sound Health Care System

Seattle, Washington, 98108, United States

Location

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

sargramostim; Colony-Stimulating Factors; Biopsy

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Shaveta Vinayak

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

• Rafael Santana-Davila

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 18, 2022
• First Posted: February 16, 2022
• Study Start: March 24, 2023
• Primary Completion: August 13, 2024
• Study Completion (Estimated): December 31, 2026
• Last Updated: August 24, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)