STEMVAC Vaccine for Lung Cancer

Not currently recruiting at 1 trial location

Overseen By Jennifer Childs

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Washington

Must be taking: Pembrolizumab

Must not be taking: Immunosuppressants

Disqualifiers: Cardiac conditions, Untreated CNS metastasis, Autoimmune disease, others

Stay on Your Current Meds You can continue your current medications while participating

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 7

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new vaccine, STEMVAC, designed to help the body fight stage IV non-small cell lung cancer. The vaccine teaches the immune system to recognize and attack specific proteins found in lung cancer cells. Participants will receive the vaccine along with a substance to boost their immune response while continuing their usual cancer maintenance therapy. Individuals with stage IV non-small cell lung cancer who have completed several rounds of specific treatments and are willing to undergo biopsies might be suitable for this study. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important advancements in cancer therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that you should not be on systemic steroids unless they are part of chemotherapy or for preventing IV contrast reactions. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the STEMVAC vaccine, a treatment for advanced lung cancer, is being tested for safety and effectiveness. This vaccine helps the immune system identify and destroy cancer cells. Studies have found that DNA vaccines like STEMVAC are generally safe, with most patients experiencing no serious side effects. Reported side effects are typically mild, such as redness or swelling at the injection site. As this trial is in a later stage, substantial data indicates its safety in human trials. However, participating in any trial carries some risks, so discussing potential side effects and benefits with a doctor is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for lung cancer?

Researchers are excited about the STEMVAC vaccine for lung cancer because it targets cancer stem cells using a novel polyepitope plasmid DNA approach. Unlike traditional treatments like chemotherapy and radiation, which attack rapidly dividing cells, STEMVAC specifically aims at proteins like CD105, Yb-1, SOX2, CDH3, and MDM2, potentially preventing tumor growth at its source. Additionally, the vaccine is paired with sargramostim, an immune system booster, which could enhance the body's natural defenses against cancer. This innovative strategy offers hope for more targeted and effective lung cancer treatment with potentially fewer side effects.

What evidence suggests that the STEMVAC vaccine could be effective for lung cancer?

Research has shown that the STEMVAC vaccine, a treatment in this trial, targets proteins that aid lung cancer cell growth and may shrink tumors in patients with stage IV non-small cell lung cancer (NSCLC). Early results suggest that DNA vaccines like STEMVAC can enhance the immune system's ability to fight cancer cells. In animal studies, similar vaccines successfully triggered strong immune responses. Additionally, past clinical trials with DNA vaccines demonstrated they are generally safe and can create targeted immune responses. These findings support STEMVAC's potential in treating advanced lung cancer. ^{1 2 3 4 6}

Who Is on the Research Team?

Shaveta Vinayak

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Rafael Santana-Davila, MD

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Are You a Good Fit for This Trial?

Adults with stage IV non-squamous NSCLC who've completed certain chemotherapy and immunotherapy without disease progression. They must have good organ function, no severe autoimmune diseases or untreated brain metastases, not be pregnant/breastfeeding, and agree to use contraception.

Inclusion Criteria

I have recovered from major infections or surgeries and don't have other serious illnesses.

My cancer can be measured by scans and has grown even after radiation.

I am willing to have two biopsies during the study.

Exclusion Criteria

Patients who are pregnant or breastfeeding

I have brain metastases that are stable, untreated, or not worsening, and I haven't taken steroids for 2 weeks.

I have serious heart conditions, including unstable chest pain or heart failure.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive STEMVAC and sargramostim intradermally on day 14 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

12 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with blood sample collection and CT scans

Up to 5 years

2 visits per year (in-person)

What Are the Treatments Tested in This Trial?

Interventions

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

Trial Overview The trial is testing STEMVAC, a DNA vaccine targeting proteins that help lung cancer grow. It's given with GM-CSF as an adjuvant to boost immune response. The goal is to see if this combination can shrink tumors in patients on maintenance therapy for NSCLC.

How Is the Trial Designed?

Group I: Arm I (STEMVAC, sargramostim) Experimental Treatment 5 Interventions

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.

Group II: Arm II (sargramostim) Active Control 4 Interventions

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.

CD105/Yb-1/SOX2/CDH3/MDM2-polyepitope Plasmid DNA Vaccine is already approved in United States for the following indications:

Approved in United States as STEMVAC for:

• Triple Negative Breast Cancer
• Non-Small Cell Lung Cancer

Who Is Running the Clinical Trial?

University of Washington

Lead Sponsor

Trials

1,858

Recruited

2,023,000+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Published Research Related to This Trial

Vaccination with a plasmid DNA encoding the SOX6 protein successfully generated specific cytotoxic T-lymphocyte (CTL) responses in glioma-bearing mice, indicating its potential as an effective immunotherapy target.

The SOX6-DNA vaccine demonstrated both protective and therapeutic antitumor effects, which were dependent on the presence of CD4 and CD8 T cells, highlighting the importance of these immune cells in combating glioma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Induction of protective and therapeutic antitumor immunity by a DNA vaccine with a glioma antigen, SOX6. Ueda, R., Kinoshita, E., Ito, R., et al.[2016]

The study developed a novel DNA vaccine (pScFvDEC-MeHer2) targeting HER2 overexpression in breast cancer, which showed a strong immune response in mice, including significant increases in IgG and IFN-γ levels.

The pScFvDEC-MeHer2 vaccine was more effective than the standard pMeHer2 vaccine in eliciting T-cell responses, indicating its potential as a promising candidate for further research in HER2-positive breast cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunogenicity of a xenogeneic multi-epitope HER2+ breast cancer DNA vaccine targeting the dendritic cell restricted antigen-uptake receptor DEC205. Gül, A., Döşkaya, M., Can, H., et al.[2022]

In a study of non-small cell lung carcinoma (NSCLC) patients, nearly 50% showed T-cell responses against the SOX2 antigen, which were linked to positive clinical responses to anti-PD-1 immunotherapy.

Patients without SOX2-specific T cells did not experience disease regression, highlighting the importance of SOX2 as a tumor-associated antigen and suggesting that targeting it may enhance the efficacy of immunotherapy in NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SOX2-specific adaptive immunity and response to immunotherapy in non-small cell lung cancer. Dhodapkar, KM., Gettinger, SN., Das, R., et al.[2021]

SOX-4 is significantly overexpressed in various types of lung cancer, including small cell lung carcinoma (SCLC) and other non-small cell lung cancers, indicating its potential as a target for lung cancer vaccines.

The study found that both CD4 and CD8 T cells in healthy donors can recognize SOX-4, and SCLC patients have SOX-4-specific antibodies, suggesting that SOX-4 could be used to develop effective vaccination strategies against lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular and immunological evaluation of the transcription factor SOX-4 as a lung tumor vaccine antigen. Friedman, RS., Bangur, CS., Zasloff, EJ., et al.[2019]

A novel polyepitope DNA vaccine targeting breast cancer-specific antigens HER2 and Mammaglobin-1 was developed, showing potential for inducing a T-cell-mediated immune response to selectively eliminate tumor cells.

The vaccine was successfully delivered into dendritic cells, which are crucial for initiating immune responses, and the expression of the target antigens was confirmed, indicating the vaccine's potential effectiveness in cancer immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Design of Polyepitope DNA Vaccine against Breast Carcinoma Cells and Analysis of Its Expression in Dendritic Cells. Nazarkina, ZhK., Khar'kova, MV., Antonets, DV., et al.[2016]

The phase 1 trial of CDX-1401, a vaccine targeting dendritic cells with the tumor antigen NY-ESO-1, showed it was safe with no severe toxicities reported, and it successfully induced immune responses in patients with advanced cancers.

Out of 45 patients, 13 experienced disease stabilization for an average of 6.7 months, and two patients had significant tumor shrinkage, suggesting that CDX-1401 could be an effective component in combination with other immunotherapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Induction of antigen-specific immunity with a vaccine targeting NY-ESO-1 to the dendritic cell receptor DEC-205. Dhodapkar, MV., Sznol, M., Zhao, B., et al.[2021]

In a study using mice, a genetic vaccine (plasmid DNA) targeting the NY-ESO-1 antigen was found to effectively induce a protective immune response against tumors, while a full-length protein vaccine did not show similar efficacy.

The research emphasizes that both the choice of antigen and the vaccine format are crucial for developing effective cancer vaccines, suggesting that peptide vaccines combined with specific adjuvants can also offer anti-tumor protection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The form of NY-ESO-1 antigen has an impact on the clinical efficacy of anti-tumor vaccination. Parvanova, I., Rettig, L., Knuth, A., et al.[2011]

DNA-based cancer vaccines can effectively induce immunity against tumor-associated antigens (TAAs) by delivering a recombinant plasmid that produces multiple epitopes, which are then presented to CD8+ T-lymphocytes.

This polyepitope approach allows for a broader immune response by including various immunogenic epitopes and accommodating patients with different MHC haplotypes, potentially enhancing the vaccine's effectiveness across diverse patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TAA polyepitope DNA-based vaccines: a potential tool for cancer therapy. Bei, R., Scardino, A.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05242965

A Multiple Antigen Vaccine (STEMVAC) for the Treatment ... 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 ...

2. withpower.com withpower.com/trial/phase-2-stage-ivb-lung-cancer-ajcc-v8-6-2022-18c95

STEMVAC Vaccine for Lung Cancer · Info for Participants Vaccination with a plasmid DNA encoding the SOX6 protein successfully generated specific cytotoxic T-lymphocyte (CTL) responses in glioma-bearing mice, ...

3. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2021-14159

A Multiple Antigen Vaccine (STEMVAC) for the Treatment ... 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 ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12230023/

Lung cancer vaccine strategies: exploring the spectrum from ... This trial evaluates the efficacy of the polyepitope plasmid DNA vaccine (STEMVAC) in reducing tumor size in patients with stage IV NSCLC. NCT06928922, I, 22 ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6449928/

Cancer DNA vaccines: current preclinical and clinical ... In the past, several clinical trials using plasmid DNA vaccines demonstrated a good safety profile and the activation of a broad and specific immune response.

6. jbiomedsci.biomedcentral.com jbiomedsci.biomedcentral.com/articles/10.1186/s12929-024-01102-w

Advances in nucleic acid-based cancer vaccines The DNA plasmid-based therapeutic vaccine STEMVAC is currently being tested in multiple clinical trials targeting different cancer types ...