Vaccine for Breast Cancer

Overseen by George T Budd, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase < 1

Recruiting

Sponsor: George T. Budd

Must be taking: Pembrolizumab

Must not be taking: Oral contraceptives

Disqualifiers: HIV, Pregnancy, Hyperprolactinemia, others

Stay on Your Current Meds

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial is testing a new vaccine to help the immune system fight breast cancer in patients who are at high risk or have already been treated for triple-negative breast cancer. The vaccine works by teaching the body's defense system to recognize and attack cancer cells.

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.

What data supports the effectiveness of the treatment for breast cancer?

Research shows that the α-lactalbumin vaccine, part of the treatment, has been effective in mouse models for preventing and treating breast cancer by targeting a protein found in most breast cancers. This suggests it could offer safe and effective protection against breast cancer in women, especially those at high risk. ^{1 2 3 4 5}

Is the α-lactalbumin vaccine safe for humans?

Research in mice suggests that the α-lactalbumin vaccine may be safe, as it did not cause inflammation in normal breast tissue when used to prevent breast cancer. However, human trials are needed to confirm its safety in people. ^{2 3 5 6 7}

How does this breast cancer vaccine treatment differ from other treatments?

This breast cancer vaccine targets a specific protein called alpha-lactalbumin, which is mostly found in breast cancer cells and not in normal tissues except during lactation. This makes it unique because it aims to prevent breast cancer by training the immune system to recognize and attack these cancer cells, potentially offering a safe and effective way to prevent the disease in women who are not lactating. ^{1 2 3 8 9}

Research Team

George T Budd, MD

Principal Investigator

Cleveland Clinic, Case Comprehensive Cancer Center

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Zymosan ()
• α-lactalbumin vaccine (Cancer 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.

Participant Groups

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+

Pete Hegseth

United States Department of Defense

Chief Executive Officer

Bachelor's degree in Political Science from Princeton University, JD from Harvard Law School

Lisa Hershman

United States Department of Defense

Chief Medical Officer since 2021

MD from Uniformed Services University of the Health Sciences

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Breast cancer vaccines for treatment and prevention. [2022]

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

An autoimmune-mediated strategy for prophylactic breast cancer vaccination. [2021]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Targeted Vaccination against Human α-Lactalbumin for Immunotherapy and Primary Immunoprevention of Triple Negative Breast Cancer. [2020]

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

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

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

Mammaglobin-A is a target for breast cancer vaccination. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Serum human alpha-lactalbumin as a marker for breast cancer. [2019]

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

Influenza vaccination in patients with breast cancer: a case-series analysis. [2006]

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

Toward a breast cancer vaccine: work in progress. [2015]

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

Outlining novel cellular adjuvant products for therapeutic vaccines against cancer. [2011]