Vaccine for Breast Cancer

Overseen By George T Budd, MD

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: George T. Budd

Must be taking: Pembrolizumab

Must not be taking: Oral contraceptives

Disqualifiers: HIV, Pregnancy, Hyperprolactinemia, 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: 12

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new breast cancer vaccine for individuals with triple-negative breast cancer, those at risk, and those completing certain treatments. The study primarily aims to determine a safe and effective vaccine dose. Participants will receive the vaccine with zymosan (an adjuvant) to evaluate its efficacy and impact on the immune system. Suitable candidates include those who have had triple-negative breast cancer and are considered high risk, or those with a genetic predisposition to this cancer type. As an Early Phase 1 trial, participants will be among the first to receive this vaccine, aiding in understanding its safety and initial immune effects.

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 must not use alternative therapies from the time you consent to 30 days after the last vaccine dose. A 'washout' period (time without taking certain medications) may be required before the first vaccine dose to ensure no alternative therapies are in use.

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

Research shows that a combination of two substances, α-lactalbumin and zymosan, is being tested for safety in treating triple-negative breast cancer. In this early-stage study, participants receive different doses to determine the safest and most effective amount. Although detailed information about side effects is not yet available, the study closely monitors safety.

In similar early-stage trials for other conditions, researchers typically start with low doses and gradually increase them. This approach helps identify potential side effects at different levels. If the treatment proves unsafe, the study does not proceed to higher doses. Therefore, being in an early phase means that safety remains under careful scrutiny. Participants should expect close monitoring for any reactions or side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the α-lactalbumin and zymosan vaccine for breast cancer because it offers a novel approach by stimulating the immune system to target cancer cells. Unlike traditional treatments like chemotherapy and radiation that attack both healthy and cancerous cells, this vaccine aims to enhance the body's natural defenses specifically against cancer cells, potentially leading to fewer side effects. Additionally, the vaccine is designed to work in conjunction with existing therapies, like pembrolizumab, to enhance effectiveness. This innovative strategy could not only improve patient outcomes but also pave the way for preventive measures in high-risk individuals.

What evidence suggests that this trial's treatments could be effective for triple-negative breast cancer?

Research has shown that the α-lactalbumin vaccine, one of the treatments in this trial, could help prevent and treat triple-negative breast cancer (TNBC). Studies found that the vaccine triggered an immune response in about 75% of women who received it, suggesting it can help the body fight cancer cells. The α-lactalbumin protein appears in most TNBC cases, making it a good target for the immune system. Animal studies indicate that activating the immune system against α-lactalbumin can prevent breast tumors. Zymosan, used with the vaccine in this trial, strengthens this immune response, potentially making the treatment more effective. ^{6 7 8 9 10}

Who Is on the Research Team?

George T Budd, MD

Principal Investigator

Cleveland Clinic, Case Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with non-metastatic triple-negative breast cancer who have completed initial treatment within the last 36 months, or those at high risk of developing such cancer. Participants must not be pregnant, breastfeeding, or using hormonal contraception and should have no recent history of chemotherapy or radiation therapy. They need normal organ function and cannot be on immunosuppressants.

Inclusion Criteria

My blood tests show my organs are functioning well.

My breast cancer diagnosis was confirmed through a biopsy.

Treatment prior to enrollment must be consistent with NCCN guidelines extant at the time treatment was given, found at: https://www.nccn.org/.

Exclusion Criteria

Active or planned lactation or pregnancy.

Subjects with known hyperprolactinemia.

I have not had radiation therapy in the last 4 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive α-lactalbumin and zymosan vaccinations every 2 weeks in a dose-escalation design to determine the Maximum Tolerated Dose (MTD) and Lowest Immunologic Dose (LID).

12 weeks

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with toxicity assessments every 2 weeks until day 56 and at day 84.

12 weeks

6 visits (in-person)

Long-term follow-up

Participants are offered participation in long-term follow-up involving contact or in-person follow-up for late toxicity and survival every 3 months for 2 years, every 6 months for an additional 3 years, and then annually for 10 years.

15 years

What Are the Treatments Tested in This Trial?

Interventions

• Zymosan
• α-lactalbumin vaccine

Trial Overview The study tests the safety and optimal dose of an alpha-lactalbumin vaccine in treating patients free from metastatic triple-negative breast cancer but at risk for recurrence, as well as preventing it in high-risk individuals. It also includes participants receiving adjuvant pembrolizumab after initial treatment.

How Is the Trial Designed?

Group I: Treatment α-lactalbumin and zymosan Experimental Treatment 2 Interventions

Participants diagnosed with triple negative breast cancer will be treated with successively higher doses of α-lactalbumin and zymosan in a 3 + 3 trial design. Treatment will involve 3 vaccinations every 2 weeks. Participants will be enrolled into 1 of 5 different dose levels each comprised of cohorts of 1-6 participants until the MTD has been identified (intra-patient dose escalation not permitted), after which the MTD will be expanded to 6 participants. Successively lower doses will be expanded to 6 participants until the lowest DL associated with immune response has been expanded. DL1: 10 mcg a-lactalbumin + 10 mcg Zymosan Original DL2:100 mcg a-lactalbumin + 100 mcg Zyomsan DL2: 100 mcg a-lactalbumin + 10 mcg Zyomsan DL3: 500 mcg a-lactalbumin + 10 mcg Zymosan DL1b: 50 mcg a-lactalbumin + 10 mcg Zymosan DL1e: 10 mcg a-lactalbumin + 20 mcg Zymosan DL1f: 20 mcg a-lactalbumin + 10 mcg Zymosan DL1g: 20 mcg a-lactalbumin + 10 mcg Zymosan (if DL1e is too toxic)

Group II: Standard of Care with a-lactalbumin and zymosan Experimental Treatment 2 Interventions

Participants undergoing chemo-immunotherapy for operable triple-negative breast cancer will be treated with α-lactalbumin concurrently with standard of care adjuvant pembrolizumab after having completed all pre- and postoperative chemotherapy and radiation therapy, with the exception of Xeloda/capecitabine at provider discretion. Treatment will involve 3 vaccinations every 2 weeks. Participants enrolled in the Pembrolizumab cohort will be enrolled at the proper Optimal Immunologic Dose as defined by the TNBC and preventative cohorts and based on information available at the time of study entry. DL1: 10 mcg a-lactalbumin + 10 mcg Zymosan Original DL2:100 mcg a-lactalbumin + 100 mcg Zyomsan DL2: 100 mcg a-lactalbumin + 10 mcg Zyomsan DL3: 500 mcg a-lactalbumin + 10 mcg Zymosan DL1b: 50 mcg a-lactalbumin + 10 mcg Zymosan DL1e: 10 mcg a-lactalbumin + 20 mcg Zymosan DL1f: 20 mcg a-lactalbumin + 10 mcg Zymosan DL1g: 20 mcg a-lactalbumin + 10 mcg Zymosan (if DL1e is too toxic)

Group III: Preventitive a-lactalbumin and zymosan Experimental Treatment 2 Interventions

Participants with a genetic risk for developing TNBC who plan to undergo prophylactic mastectomy will be treated with α-lactalbumin and zymosan at doses based on the TNBC cohort. Treatment will involve 3 vaccinations every 2 weeks. Participants enrolled in the prevention cohort will be enrolled at the dose level being used in the TNBC cohort if no DLTs above Grade 1 have been observed. If the TNBC cohort proceeds to the next dose level before another prevention cohort patient is enrolled, the next prevention patient will be enrolled on the next dose level along with the TNBC cohort. DL1: 10 mcg a-lactalbumin + 10 mcg Zymosan Original DL2:100 mcg a-lactalbumin + 100 mcg Zyomsan DL2: 100 mcg a-lactalbumin + 10 mcg Zyomsan DL3: 500 mcg a-lactalbumin + 10 mcg Zymosan DL1b: 50 mcg a-lactalbumin + 10 mcg Zymosan DL1e: 10 mcg a-lactalbumin + 20 mcg Zymosan DL1f: 20 mcg a-lactalbumin + 10 mcg Zymosan DL1g: 20 mcg a-lactalbumin + 10 mcg Zymosan (if DL1e is too toxic)

Who Is Running the Clinical Trial?

George T. Budd

Lead Sponsor

Trials

1

Recruited

50+

Anixa Biosciences, Inc.

Collaborator

Trials

2

Recruited

60+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Published Research Related to This Trial

Elevated serum levels of alpha-lactalbumin were found in 87% of women in their third trimester of pregnancy and in 64% of breast cancer patients, indicating its potential as a biomarker for breast cancer.

The study demonstrated that alpha-lactalbumin levels were significantly higher in breast cancer patients compared to men and non-pregnant women, with higher levels observed in advanced stage IV breast cancer, suggesting its utility in monitoring disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serum human alpha-lactalbumin as a marker for breast cancer. Thean, ET., Toh, BH.[2019]

Influenza vaccination is safe and well tolerated in patients with breast cancer, as shown in a study of 146 patients, with a response rate of 47.2% for the vaccine.

Patients undergoing chemotherapy had a lower immune response to the vaccine, indicating that while vaccination is recommended for all breast cancer patients, those on chemotherapy may not respond as effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influenza vaccination in patients with breast cancer: a case-series analysis. Vilar-Compte, D., Cornejo, P., Valle-Salinas, A., et al.[2006]

Breast cancer immunotherapy, particularly therapeutic vaccines, is being explored as a potential treatment option due to the severe side effects associated with conventional therapies, but no breast cancer vaccine has yet been approved for clinical use.

Current breast cancer vaccine strategies, including protein/peptide, dendritic cell, and genetic vaccines, often fail to provide clinical benefits on their own and are typically used in combination with other treatments like chemotherapy or radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cancer vaccines as a targeted immunotherapy approach for breast cancer: an update of clinical evidence. Abbaspour, M., Akbari, V.[2022]

Breast cancer vaccines have been developed to enhance immune responses against the disease, but large clinical trials have not yet shown significant improvements in progression-free or overall survival rates.

Current research is focusing on combining breast cancer vaccines with other therapies and exploring their use in preventing relapse or even the initial development of breast cancer, particularly in high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Breast cancer vaccines for treatment and prevention. Disis, ML., Cecil, DL.[2022]

Cancer vaccines offer a highly specific and less toxic treatment option for breast cancer by targeting tumor-specific antigens, which can lead to effective immune responses against the cancer.

Immunotherapy not only provides a unique mechanism of action that can overcome drug resistance seen in traditional therapies but also has the potential for long-lasting effects through immunologic memory, making it a promising avenue for both treatment and prevention of breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toward a breast cancer vaccine: work in progress. Emens, LA., Jaffee, EM.[2015]

Vaccination against α-lactalbumin, a self-protein that is normally expressed only during late pregnancy and lactation, shows promise as a safe and effective strategy for preventing and treating triple negative breast cancer (TNBC), which is particularly aggressive and common in women with BRCA1 mutations.

Preclinical data supports the potential of α-lactalbumin as a vaccine target, suggesting it could induce a strong immune response for both primary prevention and therapeutic intervention against TNBC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted Vaccination against Human α-Lactalbumin for Immunotherapy and Primary Immunoprevention of Triple Negative Breast Cancer. Tuohy, VK., Jaini, R., Johnson, JM., et al.[2020]

A novel prophylactic cancer vaccine targeting alpha-lactalbumin showed significant protection against breast tumors in mouse models, indicating its potential as a safe and effective preventive measure against breast cancer.

The vaccine's design minimizes autoimmune risks by utilizing alpha-lactalbumin, which is only expressed during lactation, allowing for vaccination without inflammation in nonlactating breast tissue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An autoimmune-mediated strategy for prophylactic breast cancer vaccination. Jaini, R., Kesaraju, P., Johnson, JM., et al.[2021]

A phase 1 clinical trial has shown that the mammaglobin-A DNA vaccine is safe for patients with metastatic breast cancer, indicating its potential for further development.

Currently, a phase 1b trial is enrolling early-stage breast cancer patients to assess the vaccine's effects when given alongside neoadjuvant endocrine therapy, allowing researchers to study its impact on the tumor microenvironment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mammaglobin-A is a target for breast cancer vaccination. Kim, SW., Goedegebuure, P., Gillanders, WE.[2021]

Despite the availability of new adjuvants, aluminum-based compounds are still predominantly used in vaccines, highlighting the need for better alternatives, especially for recombinant subunit vaccines.

Pharmaceutical companies are actively developing and testing new cellular adjuvants aimed at enhancing T-cell immunity for cancer treatments, with several products already in clinical trials for cancers like melanoma and non-small-cell lung carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outlining novel cellular adjuvant products for therapeutic vaccines against cancer. Tefit, JN., Serra, V.[2011]

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