MUC1 Vaccine + PolyICLC for Non-Small Cell Lung Cancer

Overseen By Judy Forster, RN, BSN, BS

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Olivera Finn

Must not be taking: Steroids, Anti-immune therapy

Disqualifiers: HIV, Autoimmune disease, Hepatitis B/C, 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)

Compensation: Varies

Number of Visits: 3

Duration: 9 weeks

30 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial involves giving a special vaccine to patients with non-small cell lung cancer. The vaccine aims to help the immune system recognize and attack cancer cells. The goal is to see if this approach can effectively boost the body's natural defenses against lung cancer.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot be on steroids or other anti-immune therapy. You also cannot be on any other investigational agents.

What data supports the effectiveness of the MUC1 Vaccine + PolyICLC treatment for non-small cell lung cancer?

Research shows that a similar MUC1 peptide vaccine, L-BLP25, has shown promising results in improving survival in patients with non-small cell lung cancer. Additionally, MUC1-based vaccines have been effective in generating immune responses and reducing tumor burden in preclinical studies. ^{1 2 3 4 5}

Is the MUC1 Vaccine + PolyICLC safe for humans?

The MUC1 vaccine, tested in various forms and conditions, has shown an excellent safety profile in multiple studies, with only mild and self-limiting side effects like flu-like symptoms and injection site tenderness. No significant long-term adverse effects have been reported, making it generally safe for human use. ^{1 2 6 7 8}

What makes the MUC1 Vaccine + PolyICLC treatment unique for non-small cell lung cancer?

The MUC1 Vaccine + PolyICLC treatment is unique because it targets the MUC1 protein, which is often overexpressed in cancer cells, and aims to stimulate the immune system to attack these cells. This approach is different from traditional treatments like chemotherapy, as it focuses on enhancing the body's immune response specifically against cancer cells, potentially leading to fewer side effects. ^{1 3 7 9 10}

Research Team

Arjun Pennathur, MD

Principal Investigator

University of Pittsburgh Medical Center

Eligibility Criteria

This trial is for adults with stable non-small cell lung cancer who are within 4-24 weeks post-standard treatment. They must have good organ and marrow function, no autoimmune diseases, not be on immune therapies or steroids, and agree to use contraception. Those with a history of certain cancers or serious illnesses are excluded.

Inclusion Criteria

My disease has not worsened recently.

I am fully active or can carry out light work.

My blood tests show my organs are functioning well.

Exclusion Criteria

I have never had cancer, except possibly for non-melanoma skin cancer.

I am not taking steroids or any immune system treatments currently.

Subjects may not be receiving any other investigational agents

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive the MUC1 peptide vaccine with Poly-ICLC subcutaneously every 3 weeks for 3 cycles

9 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including immunologic response and survival

2 years

Extension

Optional yearly booster vaccines for confirmed responders up to 5 years post last vaccine

5 years

Treatment Details

Interventions

• Vaccine + PolyICLC

Trial Overview The study tests a MUC1 peptide vaccine combined with PolyICLC given subcutaneously every three weeks for three doses, plus optional yearly boosters up to five years for responders. It aims to stimulate an immune response against lung cancer cells without causing significant toxicity.

Participant Groups

Group I: Stage IIIA or IIIB Experimental Treatment 1 Intervention

Concomitant chemo-irradiation followed by 3 cycles of vaccine + PolyICLC.

Group II: Stage IB/II/IIIA Experimental Treatment 1 Intervention

Resection and adjuvant chemotherapy followed by 3 cycles of vaccine + PolyICLC.

Group III: Stage IA or I/II NSCLC or neuroendocrine carcinoid tumor Experimental Treatment 1 Intervention

Resection or radiotherapy without adjuvant chemotherapy followed by 3 cycles of vaccine + PolyICLC.

Who Is Running the Clinical Trial?

Olivera Finn

Lead Sponsor

Trials

2

Recruited

40+

Findings from Research

L-BLP25, a peptide vaccine targeting the MUC1 protein, has shown a strong safety profile and induced a significant immune response in preclinical studies, leading to T-cell proliferation and IFN-gamma production.

In a randomized phase II trial for patients with stage IIIB/IV non-small cell lung cancer, L-BLP25 demonstrated a median survival of 30.6 months compared to 13.3 months for best supportive care, particularly benefiting those with locoregional stage IIIB disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

L-BLP25: a peptide vaccine strategy in non small cell lung cancer. Sangha, R., Butts, C.[2020]

Three different vaccines targeting the MUC1 tumor-associated antigen were tested for their ability to boost immunity and reject tumors in mice, revealing that only the dendritic cell (DC) vaccine effectively induced T cell immunity and led to tumor rejection.

While adjuvant-based vaccines generated antibody responses, they did not stimulate T cell responses or prevent tumor growth, highlighting the importance of T cell-mediated immunity for effective cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Three different vaccines based on the 140-amino acid MUC1 peptide with seven tandemly repeated tumor-specific epitopes elicit distinct immune effector mechanisms in wild-type versus MUC1-transgenic mice with different potential for tumor rejection. Soares, MM., Mehta, V., Finn, OJ.[2022]

The MUC1-based tricomponent vaccine, when combined with the adjuvant fibroblast stimulating lipopeptide 1 (FSL-1), successfully triggered both humoral and cellular immune responses against cancer cells.

This vaccine not only generated antibodies that effectively targeted MCF-7 tumor cells but also significantly reduced tumor burden, indicating its potential efficacy as an antitumor treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Design of a MUC1-based tricomponent vaccine adjuvanted with FSL-1 for cancer immunotherapy. Li, M., Wang, Z., Yan, B., et al.[2020]

Vaccines designed to enhance tumor antigen recognition in non-small cell lung cancer patients show promising results, including prolonged stable disease and tumor shrinkage, with no reported toxicity.

Specific vaccines such as LBLP25, TGF-beta2 antisense gene vaccine, and GVAX have demonstrated potential benefits that warrant further Phase III clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review of vaccine clinical trials for non-small cell lung cancer. Nemunaitis, J., Nemunaitis, J.[2019]

The study developed a Variable Epitope Library (VEL) vaccine platform targeting MUC1, an overexpressed antigen in tumors, which showed promising results in reducing tumor size compared to traditional wild-type peptide treatments.

Vaccination with the VEL immunogens not only reduced tumor area but also decreased lung metastasis and generated a strong CD8+ T cell response, indicating potential for effective cancer immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor efficacy of MUC1-derived variable epitope library treatments in a mouse model of breast cancer. Odales, J., Servín-Blanco, R., Martínez-Cortés, F., et al.[2022]

In a study involving 13 breast cancer patients, a MUC1 peptide immunotherapy showed no significant toxicity, except for mild reactions to the diphtheria carrier, indicating a favorable safety profile.

Although the MUC1 peptide was safe, it did not elicit strong immune responses, suggesting that while it is a potential target for immunotherapy, its current formulation may need optimization to enhance immunogenicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase-I study of synthetic muc1 peptides in breast-cancer. Xing, P., Michael, M., Apostolopoulos, V., et al.[2019]

The BLP25 liposomal vaccine was well tolerated in patients with advanced non-small-cell lung cancer, with only mild and self-limiting side effects reported, indicating a favorable safety profile.

Immunological responses were observed, with 5 out of 12 patients generating cytotoxic T lymphocytes against MUC1-positive tumor cells, suggesting potential for further development despite no significant antitumor responses noted.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of the BLP25 (MUC1 peptide) liposomal vaccine for active specific immunotherapy in stage IIIB/IV non-small-cell lung cancer. Palmer, M., Parker, J., Modi, S., et al.[2021]

The MUC1 vaccine, combined with the SB-AS2 adjuvant, was found to be safe for patients with resected or locally advanced pancreatic cancer, with common side effects being mild flu-like symptoms and injection site reactions.

The vaccine successfully induced immune responses, evidenced by increased T-cell infiltration and MUC1-specific antibodies in some patients, with two out of 15 patients remaining alive and disease-free at follow-ups of 32 and 61 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of a MUC1 vaccine composed of different doses of MUC1 peptide with SB-AS2 adjuvant in resected and locally advanced pancreatic cancer. Ramanathan, RK., Lee, KM., McKolanis, J., et al.[2008]

MUC-1 peptide-loaded non-aggregated nanoparticles (MUC-1 peptide-PLGA-NA-NPs) are smaller and more effective at cellular uptake in macrophages compared to larger aggregated nanoparticles, which could enhance their therapeutic potential in treating non-small cell lung cancer (NSCLC).

The study suggests that these non-aggregated nanoparticles could be administered via inhalation, making them a promising candidate for further investigation in NSCLC treatment models.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-small cell lung cancer tumour antigen, MUC-1 peptide-loaded non-aggregated poly (lactide-co-glycolide) nanoparticles augmented cellular uptake in mouse professional antigen-presenting cells: optimisation and characterisation. Jyoti, K., Jain, S., Katare, OP., et al.[2020]

MUC1 is a protein that, when overexpressed and improperly modified, can trigger immune responses that may help improve survival rates in various cancers, including breast and pancreatic cancers.

Initial studies of MUC1-based vaccines have shown them to be safe and capable of inducing immune responses, suggesting they could be effective in preventing cancer recurrence and enhancing immune surveillance in high-risk individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Natural and Induced Humoral Responses to MUC1. Von Mensdorff-Pouilly, S., Moreno, M., Verheijen, RH.[2021]

References

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

L-BLP25: a peptide vaccine strategy in non small cell lung cancer. [2020]

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

Three different vaccines based on the 140-amino acid MUC1 peptide with seven tandemly repeated tumor-specific epitopes elicit distinct immune effector mechanisms in wild-type versus MUC1-transgenic mice with different potential for tumor rejection. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Design of a MUC1-based tricomponent vaccine adjuvanted with FSL-1 for cancer immunotherapy. [2020]

4. England pubmed.ncbi.nlm.nih.gov

A review of vaccine clinical trials for non-small cell lung cancer. [2019]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Antitumor efficacy of MUC1-derived variable epitope library treatments in a mouse model of breast cancer. [2022]

6. Greece pubmed.ncbi.nlm.nih.gov

Phase-I study of synthetic muc1 peptides in breast-cancer. [2019]

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

Phase I study of the BLP25 (MUC1 peptide) liposomal vaccine for active specific immunotherapy in stage IIIB/IV non-small-cell lung cancer. [2021]

8. Germany pubmed.ncbi.nlm.nih.gov

Phase I study of a MUC1 vaccine composed of different doses of MUC1 peptide with SB-AS2 adjuvant in resected and locally advanced pancreatic cancer. [2008]

9. England pubmed.ncbi.nlm.nih.gov

Non-small cell lung cancer tumour antigen, MUC-1 peptide-loaded non-aggregated poly (lactide-co-glycolide) nanoparticles augmented cellular uptake in mouse professional antigen-presenting cells: optimisation and characterisation. [2020]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Natural and Induced Humoral Responses to MUC1. [2021]