TPIV100 + Sargramostim for Breast Cancer

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of a vaccine called TPIV100 (Multi-epitope HER2 Peptide Vaccine) combined with the drug sargramostim in treating certain breast cancer patients. It targets those with HER2 positive, stage II-III breast cancer who have residual disease after pre-surgery chemotherapy. The trial aims to determine if these treatments can enhance the immune system's ability to combat cancer cells. Additionally, it seeks to understand why some patients respond better to chemotherapy when combined with other drugs. This trial may suit individuals with HER2 positive breast cancer who still have cancer remaining after initial treatment. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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.

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

Research has shown that TPIV100, a vaccine derived from a part of the HER2 protein, is safe when combined with trastuzumab in patients with HER2-positive breast cancer. Patients in earlier studies tolerated the combination well, indicating general safety.

Sargramostim has a long history of safe use. It commonly increases white blood cells after chemotherapy and is considered safe without specific restrictions. Its safe use for over 20 years in various medical situations supports its safety here as well.

Overall, current evidence suggests that both TPIV100 and sargramostim are well-tolerated and safe for patients with HER2-positive breast cancer. However, like any treatment, side effects may occur, so discussing any concerns with a healthcare provider is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the TPIV100 vaccine for breast cancer because it targets the HER2 protein with a novel multi-epitope approach. Unlike standard treatments like trastuzumab and pertuzumab, which primarily block the HER2 receptor, TPIV100 aims to stimulate the immune system to recognize and attack HER2-positive cancer cells more effectively. Additionally, when combined with sargramostim, an immune booster, TPIV100 may enhance the body's natural defense mechanisms to fight the cancer, potentially improving outcomes for patients who don't achieve a complete response with existing treatments.

What evidence suggests that this trial's treatments could be effective for HER2 positive breast cancer?

This trial will evaluate the combination of TPIV100 and Sargramostim for breast cancer. Studies have shown that TPIV100, a vaccine derived from a part of the HER2 protein, might help the body build a strong immune response to attack cancer cells with HER2. In early trials, patients with HER2-positive breast cancer who received this vaccine experienced good safety and tolerability. Sargramostim increases white blood cells after chemotherapy, boosting the immune system. Research indicates that Sargramostim can enhance the body's ability to fight cancer. In this trial, some participants will receive TPIV100 and Sargramostim, while others will receive a placebo with Sargramostim, aiming to target and destroy cancer cells more effectively than standard care alone. ^{6 7 8 9 10}

Who Is on the Research Team?

Saranya Chumsri

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8416151/

Sargramostim (rhu GM-CSF) as Cancer Therapy (Systematic ... Sargramostim accelerates hematologic recovery in diverse clinical settings and enhances anti-cancer responses with a favorable safety profile.

2. cancernetwork.com cancernetwork.com/view/continuous-low-dose-gm-csf-salvage-therapy-refractory-recurrent-breast-or-female-genital-tract

Continuous Low-Dose GM-CSF as Salvage Therapy in ... Adjuvant treatment with continuous lowdose GM-CSF has been shown to prolong survival of stage III/IV melanoma patients. Data on continuous low-dose GM-CSF ...

3. clinicaltrials.eu clinicaltrials.eu/inn/sargramostim/

Sargramostim: A Comprehensive Guide for Patients Sargramostim can help replenish these cells, thereby improving the body's ability to fight infections and potentially enhancing the effectiveness of other ...

4. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2018/103362Orig1s5240.pdf

103362Orig1s5240 - accessdata.fda.gov We have concluded that Leukine® (sargramostim) can be safely used without restrictions on distribution or use. 2. Information to be provided to ...

5. partnertx.com partnertx.com/a-drug-before-its-time-leukine-systematic-review-highlights-innate-and-adaptive-immune-activity-that-may-improve-cancer-outcomes-and-reduce-toxicity/

“A Drug Before Its Time?” LEUKINE® systematic review ... This review article highlights Leukine's potential to generate benefit for patients in numerous diseases that feature GM-CSF deficiency.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04197687

TPIV100 and Sargramostim for the Treatment of HER2 ... TPIV100 is a type of vaccine made from HER2 peptide that may help the body build an effective immune response to kill tumor cells that express HER2.

7. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2019-08038

TPIV100 and Sargramostim for the Treatment of HER2 ... This phase II trial studies how well TPIV100 and sargramostim work in treating patients with HER2 positive, stage I-III breast cancer that has residual disease ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S2666379124002672

Emerging treatments in HER2-positive advanced breast ... The addition of pertuzumab to trastuzumab and taxane demonstrated a median progression-free survival (PFS) of 18.7 months in untreated, advanced ...

9. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.TPS610

Phase II trial to evaluate immune-related biomarkers for ... In our previous phase I trial this vaccine was shown to be safe in combination with trastuzumab in stage II-III HER2+ breast cancer after ...

10. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8608270/

Therapeutic vaccines for breast cancer: Has the time finally ... After a 5-year follow up, the DFS rate in 46 HER2 IHC 3+ BC fully vaccinated patients was 100% versus 89.4% in the 50 HER2 IHC 3+ patients who received placebo ...