STEMVAC Vaccine for Lung Cancer

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

40 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a new DNA-based vaccine called STEMVAC, combined with GM-CSF, in patients with advanced lung cancer. The vaccine helps the immune system recognize and attack cancer cells, while GM-CSF boosts this response. The goal is to see if this combination can shrink tumors in these patients. GM-CSF has been used in various tumor vaccines to stimulate the immune system and enhance antitumor responses.

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.

What data supports the effectiveness of the STEMVAC Vaccine for Lung Cancer treatment?

Research shows that SOX-4, one of the components of the STEMVAC vaccine, is overexpressed in lung tumors and can trigger a strong immune response, suggesting its potential as a vaccine target. Additionally, SOX2, another component, has been linked to positive responses in lung cancer patients undergoing immunotherapy, indicating its role in enhancing immune responses against cancer. ^{1 2 3 4 5}

What makes the STEMVAC vaccine treatment unique for lung cancer?

The STEMVAC vaccine is unique because it uses a DNA-based approach to target multiple tumor-associated antigens (proteins that can trigger an immune response) simultaneously, which may enhance the immune system's ability to recognize and attack lung cancer cells. This polyepitope strategy allows for a broader immune response compared to traditional treatments that might target a single antigen. ^{1 3 6 7 8}

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

Eligibility Criteria

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.

I am 18 years old or older.

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

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Molecular and immunological evaluation of the transcription factor SOX-4 as a lung tumor vaccine antigen. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Induction of antigen-specific immunity with a vaccine targeting NY-ESO-1 to the dendritic cell receptor DEC-205. [2021]

3. Netherlands pubmed.ncbi.nlm.nih.gov

The form of NY-ESO-1 antigen has an impact on the clinical efficacy of anti-tumor vaccination. [2011]

4. United States pubmed.ncbi.nlm.nih.gov

SOX2-specific adaptive immunity and response to immunotherapy in non-small cell lung cancer. [2021]

5. Netherlands 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. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

TAA polyepitope DNA-based vaccines: a potential tool for cancer therapy. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Induction of protective and therapeutic antitumor immunity by a DNA vaccine with a glioma antigen, SOX6. [2016]

8. United States pubmed.ncbi.nlm.nih.gov

Design of Polyepitope DNA Vaccine against Breast Carcinoma Cells and Analysis of Its Expression in Dendritic Cells. [2016]