A Phase II Randomized Study of Safety and Efficacy of a Multiple Antigen Vaccine (STEMVAC) in Non-Small-Cell Lung Cancer Patients

Plain English Summary

A Multiple Antigen Vaccine (STEMVAC) for the Treatment of Patients With Stage IV Non-Small Cell Lung Cancer is a Phase 2 clinical trial sponsored by University of Washington studying Lung Non-Small Cell Carcinoma, Stage IV Lung Cancer AJCC v8. This trial tests a new DNA vaccine called STEMVAC, combined with a drug called GM-CSF, to see if it can help shrink tumors in patients with advanced non-small cell lung cancer. It is for patients with stage IV non-small cell lung cancer who have completed initial chemotherapy and immunotherapy and are stable. Participation involves receiving the vaccine and GM-CSF, undergoing regular check-ups, and potentially having biopsies and blood draws. Alternative treatments may include continued standard chemotherapy, immunotherapy, or other clinical trials. The trial aims to enroll 5 participants.

Official 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.

Who Can Participate

Here is what you need to know about eligibility for this trial. You can join if you have stage IV non-small cell lung cancer (either squamous or non-squamous type) that has spread. You must have completed 3-4 cycles of chemotherapy and immunotherapy (including pembrolizumab) without the cancer getting worse. You cannot join if you have untreated brain metastases, certain heart conditions, or active autoimmune diseases requiring immunosuppressants. This trial is studying Lung Non-Small Cell Carcinoma, Stage IV Lung Cancer AJCC v8, so participants generally need a confirmed diagnosis.

What They're Measuring

The primary outcome measures will tell us how well the vaccine activates specific immune cells (CD8 T-cells) within the tumor and how many participants experience side effects, indicating the vaccine' The specific primary outcome measures are: CD8 is Reported as a Fraction of CD3+ Tumor Infiltrating Lymphocytes (TIL) in 4 High-power Field (HPF) (Baseline and after the third vaccine (at approximately 12 weeks)); Number of Participants With Recorded Adverse Event(s) (Up to 20 weeks). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial aims to fill a treatment gap by exploring a novel vaccine approach to stimulate the immune system to fight advanced lung cancer, potentially offering a new option for patients who have comp Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Lung Non-Small Cell Carcinoma, Stage IV Lung Cancer AJCC v8, where improved treatment options are needed.

Investor Insight

This Phase II trial, sponsored by the University of Washington, investigates a novel DNA vaccine for a significant unmet need in Stage IV NSCLC, suggesting potential for future development and market Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor about the potential benefits and risks of the STEMVAC vaccine and GM-CSF, and how they might interact with your current health. Be prepared for regular clinic visits for vaccine administration, blood tests, and imaging scans to monitor your cancer and any side effects. You may need to undergo biopsies of your tumor during the study to help researchers understand how the vaccine is working. The trial is being conducted at 2 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: SEQUENTIAL
• Masking: DOUBLE
• Enrollment: 5 participants

Interventions

• BIOLOGICAL: CD105/Yb-1/SOX2/CDH3/MDM2-polyepitope Plasmid DNA Vaccine — Given ID
• BIOLOGICAL: Sargramostim — Given ID
• PROCEDURE: Computed Tomography — Undergo CT
• PROCEDURE: Biopsy — Undergo biopsy
• PROCEDURE: Biospecimen Collection — Undergo blood sample collection

Primary Outcomes

• CD8 is Reported as a Fraction of CD3+ Tumor Infiltrating Lymphocytes (TIL) in 4 High-power Field (HPF) (Baseline and after the third vaccine (at approximately 12 weeks))
• Number of Participants With Recorded Adverse Event(s) (Up to 20 weeks)

Secondary Outcomes

• 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)

Full Eligibility Criteria

Inclusion Criteria:

* 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).
* Total bilirubin =\< 1.5 mg/dl (within 60 days of first vaccination).
* Aspartate aminotransferase/serum glutamic oxaloacetic transaminase (AST/SGOT) =\< 2 times upper limit of normal (ULN) or SGOT =\< 5 times upper limit of normal (ULN) in the presence of liver metastasis (within 60 days of first vaccination).
* If female of childbearing potential has a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication.
* All patients who are having sex that can lead to pregnancy must agree to contraception for the duration of study.
* Patients must be at least 18 years of age.

Exclusion Criteria:

* 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.

Trial Locations

• University of Nebraska Medical Center, Omaha, Nebraska, United States
• Fred Hutch/University of Washington Cancer Consortium, Seattle, Washington, United States

Frequently Asked Questions

Related Conditions

• Lung Cancer
• Non-Small Cell Lung Cancer
• Stage IV Cancer
• Metastatic Lung Cancer
• Immunotherapy
• Chemotherapy
• Cancer Vaccines
• Tumor Microenvironment
• Immune Response
• Oncology

More Lung Non-Small Cell Carcinoma Trials

View all Lung Non-Small Cell Carcinoma clinical trials