TPIV100 + Sargramostim for Breast Cancer

Recruiting at 18 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Mayo Clinic

Must not be taking: Steroids, Immunosuppressants

Disqualifiers: Pregnancy, Metastases, Autoimmune, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 18 weeks

480 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a vaccine and a drug in patients with a specific type of breast cancer who still have cancer after chemotherapy. The vaccine helps the immune system target cancer cells, and the drug boosts white blood cells to strengthen this response. The goal is to see if this combination can better treat these patients.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, it mentions that patients must be off systemic steroids at least 14 days before pre-registration, and those on anticoagulant therapy must have their PT or PTT within the therapeutic range. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment TPIV100 + Sargramostim for breast cancer?

Research shows that vaccines targeting HER-2, like TPIV100, can induce strong immune responses and produce antibodies that may help fight breast cancer. Additionally, combining HER-2 vaccines with GM-CSF (a component of Sargramostim) has shown potential in enhancing the immune response and reducing tumor growth in preclinical studies. ^{1 2 3 4 5}

Is the TPIV100 + Sargramostim treatment generally safe for humans?

The treatment involving GM-CSF (Sargramostim) and HER2 peptide vaccines, similar to TPIV100, has been tested in clinical trials and shown to be generally safe, with no severe side effects reported. Some studies noted mild side effects like local redness at the injection site, but overall, the treatment was well tolerated. ^{1 4 6 7 8}

What makes the TPIV100 + Sargramostim treatment unique for breast cancer?

The TPIV100 + Sargramostim treatment is unique because it uses a multi-epitope HER2 peptide vaccine to stimulate the immune system to target HER2-positive breast cancer cells, potentially offering a more targeted approach compared to traditional therapies. This vaccine aims to induce a strong immune response by generating specific antibodies and T-cell responses against the HER2 protein, which is overexpressed in many breast cancer cases. ^{1 2 3 9 10}

Research Team

Saranya Chumsri

Principal Investigator

Mayo Clinic

Eligibility Criteria

This trial is for HER2 positive, stage II-III breast cancer patients with residual disease post-chemotherapy and surgery. Participants must have completed all planned surgeries and any radiation at least 30 days prior, have a certain level of blood cell counts, be willing to provide tissue/blood samples, use contraception if applicable, and not be pregnant. They should also have an ECOG performance status of 0-2.

Inclusion Criteria

Your hemoglobin level is at least 9.0 grams per deciliter, as measured within the past 28 days before the study starts.

Provide written informed consent

Willing to provide mandatory tissue and blood samples for correlative research purposes

Exclusion Criteria

I have taken medication like tamoxifen to prevent breast cancer within the last 2 months.

Person of child bearing potential who are unwilling to employ adequate contraception from the time of registration through 6 months after the final vaccine cycle

Your heart's pumping ability is less than 50%.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Chemotherapy

Participants receive neoadjuvant chemotherapy prior to surgery

Varies

Surgery

Participants undergo surgery to remove residual disease

1 day

Treatment

Participants receive standard of care maintenance therapy with trastuzumab emtansine and either TPIV100 or placebo, with sargramostim, every 21 days for up to 6 cycles

18 weeks

Booster Injections

Participants receive two additional booster injections of TPIV100 or placebo and sargramostim at 3 and 12 months after completion of trastuzumab emtansine maintenance therapy

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Treatment Details

Interventions

• Multi-epitope HER2 Peptide Vaccine TPIV100
• Sargramostim

Trial Overview The trial is testing the effectiveness of TPIV100 (a vaccine targeting HER2 peptides) combined with sargramostim (which boosts white blood cells) in treating breast cancer that remains after initial treatments. It's also exploring why some patients respond better to chemotherapy when paired with trastuzumab and pertuzumab.

Participant Groups

Group I: Treatment (pCR) Experimental Treatment 2 Interventions

Patients receive standard of care maintenance therapy with trastuzumab and pertuzumab for 1 year in the absence of disease progression or unacceptable toxicity.

Group II: Arm I - No pCR (trastuzumab emtansine, TPIV100, sargramostim) Experimental Treatment 3 Interventions

Patients receive standard of care maintenance therapy with trastuzumab emtansine and receive TPIV100 ID and sargramostim ID on day 1. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive two additional booster injections of TPIV100 ID and sargramostim ID at 3 and 12 months after completion of trastuzumab emtansine maintenance therapy.

Group III: Arm II - No pCR (trastuzumab emtansine, placebo, sargramostim) Placebo Group 3 Interventions

Patients receive standard of care maintenance therapy with trastuzumab emtansine and receive placebo ID and sargramostim ID on day 1. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive two additional booster injections of placebo ID and sargramostim ID at 3 and 12 months after completion of trastuzumab emtansine maintenance therapy.

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Academic and Community Cancer Research United

Lead Sponsor

Trials

54

Recruited

4,900+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

The phase I clinical trial involving 10 patients with metastatic breast cancer demonstrated that the Her-2/neu multipeptide vaccine was safe and well-tolerated, with local erythema being the only reported side effect.

The vaccine successfully induced Her-2/neu-specific antibodies in 8 out of 10 patients, suggesting potential for clinical benefit similar to existing anti-Her-2 antibody therapies, while also reducing regulatory T cells that may suppress immune responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A virosomal formulated Her-2/neu multi-peptide vaccine induces Her-2/neu-specific immune responses in patients with metastatic breast cancer: a phase I study. Wiedermann, U., Wiltschke, C., Jasinska, J., et al.[2019]

A multiepitope vaccine targeting the HER-2 oncoprotein was developed using computer-aided analysis, which showed promising results in inducing high levels of antibodies that inhibited tumor growth in rabbits.

Combining two specific chimeric vaccines enhanced immune responses, leading to a significant reduction in pulmonary metastases in a cancer model, suggesting potential for treating HER-2-associated cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A chimeric multi-human epidermal growth factor receptor-2 B cell epitope peptide vaccine mediates superior antitumor responses. Dakappagari, NK., Pyles, J., Parihar, R., et al.[2020]

A phase II trial involving 150 patients with HER2 low-expressing breast cancer showed that combining the HER2-peptide vaccine nelipepimut-S with trastuzumab did not increase toxicity compared to trastuzumab alone, indicating a favorable safety profile.

The study aims to assess the clinical efficacy of this combination therapy, with results expected 6 months after the final patient enrollment, potentially offering new treatment options for patients who currently do not benefit from HER2-targeted therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initial safety analysis of a randomized phase II trial of nelipepimut-S + GM-CSF and trastuzumab compared to trastuzumab alone to prevent recurrence in breast cancer patients with HER2 low-expressing tumors. Clifton, GT., Peace, KM., Holmes, JP., et al.[2020]

In a phase II study involving 14 patients with advanced metastatic triple-negative breast cancer, a 6-week mixed 19-peptide cancer vaccine showed no severe adverse events, indicating a favorable safety profile.

The study found that an increase in peptide-specific IgG correlated with improved overall survival, with a median overall survival of 11.5 months for all patients and 24.4 months for those who completed the vaccination, suggesting potential efficacy of the vaccine in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early phase II study of mixed 19-peptide vaccine monotherapy for refractory triple-negative breast cancer. Toh, U., Sakurai, S., Saku, S., et al.[2021]

References

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

A virosomal formulated Her-2/neu multi-peptide vaccine induces Her-2/neu-specific immune responses in patients with metastatic breast cancer: a phase I study. [2019]

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

A chimeric multi-human epidermal growth factor receptor-2 B cell epitope peptide vaccine mediates superior antitumor responses. [2020]

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

Expression of Breast Cancer-Related Epitopes Targeting the IGF-1 Receptor in Chimeric Human Parvovirus B19 Virus-Like Particles. [2020]

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

Initial safety analysis of a randomized phase II trial of nelipepimut-S + GM-CSF and trastuzumab compared to trastuzumab alone to prevent recurrence in breast cancer patients with HER2 low-expressing tumors. [2020]

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

Vaccination with ErbB-2 peptides prevents cancer stem cell expansion and suppresses the development of spontaneous tumors in MMTV-PyMT transgenic mice. [2016]

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

Early phase II study of mixed 19-peptide vaccine monotherapy for refractory triple-negative breast cancer. [2021]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Prospective, randomized, single-blinded, multi-center phase II trial of two HER2 peptide vaccines, GP2 and AE37, in breast cancer patients to prevent recurrence. [2021]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Evaluating Nelipepimut-S in the Treatment of Breast Cancer: A Short Report on the Emerging Data. [2020]

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

The impact of HER2/neu expression level on response to the E75 vaccine: from U.S. Military Cancer Institute Clinical Trials Group Study I-01 and I-02. [2020]

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

Vaccination with a HER2/neu peptide induces intra- and inter-antigenic epitope spreading in patients with early stage breast cancer. [2014]