What is the mechanism of action of this treatment?

Common treatments for breast cancer, especially HER2-positive types, often include immunotherapy approaches like HER2 peptide vaccines and agents that boost the immune system. TPIV100, a HER2 peptide vaccine, works by stimulating the body's immune response to target and destroy cancer cells expressing the HER2 protein. Sargramostim, on the other hand, increases the number of white blood cells and activates the immune system, enhancing its ability to fight cancer. These treatments are significant for breast cancer patients as they offer a targeted approach, potentially leading to more effective and personalized therapy with fewer side effects compared to traditional chemotherapy.

What side effects are associated with this type of intervention?

Common side effects of immunotherapy treatments for breast cancer, such as those involving HER2 peptide vaccines like TPIV100 and immune system boosters like Sargramostim, include fatigue, fever, chills, nausea, and injection site reactions. More severe side effects can involve immune-related adverse events such as colitis, pneumonitis, hepatitis, and endocrinopathies. Sargramostim specifically can cause bone pain, muscle aches, fever, and injection site reactions, with severe cases potentially leading to allergic reactions and capillary leak syndrome.

What prior FDA approvals exist?

The FDA has approved several treatments for HER2-positive breast cancer that involve immunotherapy and immune system activation. Trastuzumab (Herceptin) and pertuzumab (Perjeta) are monoclonal antibodies that target the HER2 receptor, enhancing the immune system's ability to attack cancer cells. Additionally, ado-trastuzumab emtansine (Kadcyla) combines trastuzumab with a chemotherapy agent to deliver targeted treatment. These therapies, like TPIV100 and Sargramostim, aim to boost the immune response against HER2-positive breast cancer cells.

What other types of research exist?

Promising novel alternatives for breast cancer treatment in 2024 include: 1) Trastuzumab Deruxtecan (Enhertu), an antibody-drug conjugate targeting HER2-positive breast cancer, which has shown significant efficacy in clinical trials. 2) Margetuximab, a HER2-targeted monoclonal antibody with enhanced immune activation properties. 3) Pembrolizumab (Keytruda), an immune checkpoint inhibitor that has shown promise in combination with other therapies for HER2-positive breast cancer. 4) Tucatinib, a small molecule tyrosine kinase inhibitor that targets HER2 and has demonstrated improved outcomes in combination with trastuzumab and capecitabine.

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Cancer Vaccine

TPIV100 + Sargramostim for Breast Cancer

Phase 2

Recruiting

Led By Saranya Chumsri

Research Sponsored by Mayo Clinic

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Histologically confirmed adenocarcinoma of the breast stage >= T2 OR >= N1 based on the 7th edition of tumor, node, metastases (TNM) staging system from the American Joint Committee on Cancer

Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, 2

Must not have

Immunocompromised patients including patients known to be human immunodeficiency virus (HIV) positive or those on chronic steroids

Nursing person unwilling to stop breast feeding

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Potential side effects may include typical vaccine-related reactions like soreness or redness at the injection site, flu-like symptoms such as fever or chills, fatigue from immune system activation by TPIV100, and possible increase in white blood cells due to sargramostim which could lead to bone pain or skin reactions.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My breast cancer is at least stage T2 or N1.

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I can take care of myself but may not be able to do heavy physical work.

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I finished my last chemotherapy cycle more than 90 days ago.

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I still have a tumor larger than 1 cm in my breast or cancer in my lymph nodes after treatment.

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I can take care of myself but may not be able to do heavy physical work.

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My cancer is HER2 positive, confirmed by specific tests.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have a weakened immune system, either due to HIV or long-term steroid use.

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I am breastfeeding and not willing to stop.

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I have not had any other cancer within the last 3 years.

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I do not have any severe illnesses or social situations that would stop me from following the study's requirements.

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I haven't had a heart attack in the last 6 months or heart failure needing ongoing treatment.

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I still have side effects from my last chemotherapy that haven't gone away.

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I had heart issues from trastuzumab treatment but my heart function has recovered.

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I have an autoimmune disease treated with medication in the last 30 days.

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My cancer has returned or spread to other parts of my body.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Invasive disease-free survival (iDFS) between the 2 arms

Secondary study objectives

Complete pathological response

Immunogenicity assessment

Incidence of adverse events (AEs)

+2 more

Side effects data

From 2014 Phase 4 trial • 32 Patients • NCT01301729

59%

Leukopenia

56%

Neutropenia

34%

Hypoaesthesia

31%

Agranulocytosis

22%

Alopecia

22%

Asthenia

19%

Pyrexia

16%

Nail disorder

16%

Oedema peripheral

16%

Diarrhoea

16%

Hypophagia

13%

Alanine aminotransferase increased

13%

Neurotoxicity

13%

Cough

13%

Vomting

Musculoskeletal pain

Aspartate aminotransferase increased

Headache

Chest discomfort

Rash

Pigmentation disorder

Nausea

Bone marrow failure

Anaemia

Transaminases increased

Insomnia

Constipation

Mouth ulceration

Nasopharyngitis

Paronychia

Flushing

Face oedema

Thrombocytopenia

Infection

Upper respiratory tract infection

Completed suicide

Cataract

100%

80%

60%

40%

20%

Study treatment Arm

Trastuzumab

Trial Design

3Treatment groups

Experimental Treatment

Placebo Group

Group I: Treatment (pCR)Experimental Treatment2 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 Treatment3 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 Group3 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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Trastuzumab

2014

Completed Phase 4

~5190

Trastuzumab Emtansine

2016

Completed Phase 3

~5730

Pertuzumab

2014

Completed Phase 3

~7500

Sargramostim

2006

Completed Phase 4

~880

0 / 15Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for breast cancer, especially HER2-positive types, often include immunotherapy approaches like HER2 peptide vaccines and agents that boost the immune system. TPIV100, a HER2 peptide vaccine, works by stimulating the body's immune response to target and destroy cancer cells expressing the HER2 protein. Sargramostim, on the other hand, increases the number of white blood cells and activates the immune system, enhancing its ability to fight cancer. These treatments are significant for breast cancer patients as they offer a targeted approach, potentially leading to more effective and personalized therapy with fewer side effects compared to traditional chemotherapy.