MUC1 Vaccine + PolyICLC for Non-Small Cell Lung Cancer

Overseen By Research Coordinator

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new vaccine combined with PolyICLC, an immune system stimulant, to determine its effectiveness for individuals with non-small cell lung cancer (NSCLC) or neuroendocrine carcinoid tumors. The goal is to assess the vaccine's efficacy and the immune system's response. Participants will receive the vaccine every three weeks for three cycles, with an option for yearly boosters if they respond well. This trial targets individuals with stable NSCLC or neuroendocrine carcinoid tumors who have completed standard treatment within the last 4 to 24 weeks. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the chance to be among the first to receive this new vaccine.

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.

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

Research has shown that the MUC1 vaccine, when combined with PolyICLC, was safe in earlier studies. These trials found no harmful side effects. The vaccine successfully activated a strong immune response in many participants. Although some studies included individuals at risk for lung cancer or other conditions, the safety results are encouraging for those considering this treatment. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for non-small cell lung cancer?

Researchers are excited about the MUC1 Vaccine combined with PolyICLC for non-small cell lung cancer because it represents a novel approach compared to traditional treatments like chemotherapy and radiation. Unlike the standard therapies that primarily attack cancer cells directly, the MUC1 Vaccine aims to stimulate the immune system to recognize and combat cancer cells more effectively, leveraging the body's natural defenses. Additionally, PolyICLC is an immune system booster that enhances the vaccine's effectiveness, potentially leading to a more robust and sustained response against the cancer. This innovative approach not only targets cancer more precisely but also has the potential to improve outcomes with fewer side effects.

What evidence suggests that this trial's treatments could be effective for non-small cell lung cancer?

Research has shown that the MUC1 vaccine, when combined with Poly-ICLC, may help treat certain cancers. In an earlier study, this combination effectively triggered an immune response in about 44% of participants. This response included high levels of specific antibodies, crucial for fighting cancer cells. The vaccine has proven safe for patients, showing no harmful effects. Specifically, previous patients with advanced adenomas, which are pre-cancerous growths, exhibited a strong immune reaction, suggesting the vaccine might help prevent further cancer development. This trial will evaluate the MUC1 vaccine with Poly-ICLC in different stages of non-small cell lung cancer, offering hope for its use in treating this condition. ^{3 4 6 7 8}

Who Is on the Research Team?

Arjun Pennathur, MD

Principal Investigator

University of Pittsburgh Medical Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT01720836?tab=history&a=13

Record History | ver. 13: 2024-05-13 | NCT01720836 An unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain amount of ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3536916/

MUC1 Vaccine for Individuals with Advanced Adenoma of ... A vaccine based on the TAA MUC1 was highly immunogenic in 17/39 (43.6%) of vaccinated individuals, eliciting high levels of anti-MUC1 IgG and long-lasting ...

3. centerwatch.com centerwatch.com/clinical-trials/listings/NCT01720836/study-of-the-immune-response-of-muc1-mucin1-peptide-vaccine-for-non-small-cell-lung-cancer

Study of the Immune Response of MUC1 (Mucin1) Peptide ... The same formulation, MUC1 100mer peptide admixed with Poly-ICLC, is used in both trials. There has been no toxicity observed and the vaccine is ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40666355/

A Multicenter Pilot Study of MUC1 Vaccine in Current and ... We explored whether a MUC1 vaccine might be effective in halting neoplastic development and progression in individuals at high risk for lung ...

5. cancer.gov cancer.gov/research/participate/clinical-trials/intervention/muc1-peptide-poly-iclc-vaccine?pn=1

Clinical Trials Using MUC1 Peptide-Poly-ICLC Vaccine - NCI Review the clinical trials studying muc1 peptide-poly-iclc vaccine on this list and use the filters to refine the results by age and location.

6. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/73337

Study of the Immune Response of MUC1 (Mucin1) Peptide ... The same formulation, MUC1 100mer peptide admixed with Poly-ICLC, is used in both trials. There has been no toxicity observed and the vaccine is highly ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03300817

NCT03300817 | MUC1 Vaccine in Preventing Lung Cancer ... This pilot phase I trial studies the side effects and how well MUC1 peptide-Poly-ICLC vaccine works in preventing lung cancer in current and former smokers ...

8. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT01720836?term=prostate+recruiting

Study of the Immune Response of MUC1 (Mucin1) Peptide ... Data collected at the beginning of a clinical study for all participants and for each arm or comparison group. These data include demographics, such as age, sex ...