Vaccine Therapy for Breast Cancer
Recruiting in Palo Alto (17 mi)
+1 other location
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Pravin T.P Kaumaya
Must not be taking: Targeted therapies
Disqualifiers: Active infection, HIV, Hepatitis, Autoimmune, others
No Placebo Group
Trial Summary
What is the purpose of this trial?
This phase I trial studies the side effects and best dose of vaccine therapy in treating patients with metastatic solid tumors. Vaccines made from antibodies and peptides combined with tumor cells may help the body build an effective immune response to kill tumor cells.
Will I have to stop taking my current medications?
The trial protocol does not specify if you need to stop taking your current medications. However, patients on certain targeted therapies or those requiring corticosteroids or other immunosuppressives are not eligible, which might imply some restrictions. It's best to discuss your specific medications with the trial team.
What data supports the effectiveness of the treatment for breast cancer?
Research suggests that combining HER2-targeted therapies with cancer vaccines can enhance the immune response against breast cancer. Specifically, combining trastuzumab (a HER2-targeted therapy) with HER2-targeted cancer vaccines has shown benefits in certain types of breast cancer, indicating potential effectiveness of similar vaccine therapies.12345
Is the MVF-HER-2 vaccine therapy for breast cancer safe for humans?
How does the MVF-HER-2 vaccine treatment for breast cancer differ from other treatments?
The MVF-HER-2 vaccine treatment is unique because it combines specific HER-2 protein segments with an adjuvant (a substance that enhances the body's immune response) to stimulate both B and T cell responses, potentially offering a more targeted and effective immune attack against breast cancer cells compared to other vaccines that may focus on a single type of immune response.59101112
Eligibility Criteria
This trial is for patients with metastatic solid tumors, specifically those with breast cancer or gastrointestinal cancers that show an overexpression of a protein called Epidermal Growth Factor Receptor (EGFR).Inclusion Criteria
I have breast or gastrointestinal cancer that cannot be removed by surgery.
I had brain metastases treated, off steroids, and stable for 3+ months.
Women of child-bearing potential must not be pregnant and must have a negative pregnancy test. Men and women must agree to practice effective contraception while on this study
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Exclusion Criteria
I am allergic to specific components used in the trial.
I have been off antibiotics for 3 weeks and am clear of infection.
Patients who have developed anaphylactic responses to other vaccines
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Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive the HER-2 B Cell Peptide Vaccine to study side effects and best dose
up to 92 days
Multiple visits for vaccine administration
Follow-up
Participants are monitored for safety and effectiveness after treatment
up to 1 year
Follow-up visits at 21 days, 6 months, and 1 year post initial vaccination
Treatment Details
Interventions
- Combination of MVF-HER-2 (597-626) and MVF-HER-2 (266-296) emulsified with ISA 720 (Cancer Vaccine)
Trial OverviewThe study is testing vaccine therapy combining two peptides, MVF-HER-2 (597-626) and MVF-HER-2 (266-296), mixed with ISA 720 to see if it can stimulate the immune system to destroy tumor cells.
Participant Groups
2Treatment groups
Experimental Treatment
Group I: HER-2 vaccine GIExperimental Treatment1 Intervention
Group II: HER-2 vaccine BreastExperimental Treatment1 Intervention
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Indiana University Melvin & Bren Simon Comprehensive Cancer CenterIndianpolis, IN
Indiana University Melvin & Bren Simon Comprehensive Cancer CenterIndianapolis, IN
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Who Is Running the Clinical Trial?
Pravin T.P KaumayaLead Sponsor
References
[Enhanced inhibitory effect of MUC1 gene vaccine on breast cancer growth by GM-CSF]. [2019]To investigate if GM-CSF adjuvant could enhance the inhibitory effect of the MUC1 gene vaccine on EMT6 breast cancer growth.
Immunotherapy as a partner for HER2-directed therapies. [2022]Introduction: Existing HER2-targeted therapies modulate the tumor microenvironment and the immunologic response cancer in a favorable way. While these therapies have made dramatic improvements in the treatment and prognosis of HER2-overexpressing malignancies, additional treatment options are still needed.Areas covered: This review covers the immunomodulatory effects of approved HER2-targeted therapies. We discuss the preclinical data that demonstrate an additive effect of the combination of trastuzumab or other HER2-targeting agents with immunomodulatory drugs. Finally, we report the initial studies on the combination of HER2-targeted agents together with immune checkpoint inhibitors or cancer vaccines in breast cancer.Expert opinion: Preclinical data suggest a synergistic effect of HER2-targeted therapy together with both checkpoint inhibitor and cancer vaccine immunotherapy. Results from initial trials with PD-1/PD-L1-blocking therapy together with HER2-targeted therapy have been negative, but responses were seen in patients with PD-L1+ breast cancer. Trastuzumab together with HER2-targeted cancer vaccination has shown benefits in triple negative breast cancer. Further trials are necessary and warranted to confirm the benefit of these combinations.
Efficacy and Safety Analysis of Nelipepimut-S Vaccine to Prevent Breast Cancer Recurrence: A Randomized, Multicenter, Phase III Clinical Trial. [2020]In phase I/II studies, nelipepimut-S (NP-S) plus GM-CSF vaccine was well tolerated and effectively raised HER2-specific immunity in patients with breast cancer. Results from a prespecified interim analysis of a phase III trial assessing NP-S + GM-CSF are reported.
Emerging strategies for the dual inhibition of HER2-positive breast cancer. [2019]To review the recently published trials to help us refine and optimize the use of approved HER2-targeted agents (trastuzumab and lapatinib) and highlight future combination strategies for the treatment of HER2-positive breast cancer.
Application of HER2 peptide vaccines in patients with breast cancer: a systematic review and meta-analysis. [2021]The E75 and GP2 vaccines are the few therapeutic vaccines targeting HER2 currently under clinical research for patients with breast cancer.
A phase I/II trial of the safety and clinical activity of a HER2-protein based immunotherapeutic for treating women with HER2-positive metastatic breast cancer. [2021]The objectives of this phase I/II study (NCT00140738) were to evaluate the safety and clinical activity of a cancer immunotherapeutic agent (recombinant HER2 protein (dHER2) and the immunostimulant AS15) in patients with HER2-overexpressing metastatic breast cancer (MBC). Forty HER2-positive MBC patients received up to 18 doses (12q2w, 6q3w) of dHER2 immunotherapeutic, as first- or second-line therapy following response to trastuzumab-based treatment as maintenance. Toxicity was graded by the Common Terminology Criteria for Adverse Events (CTCAE) and clinical activity was evaluated by target lesion assessment according to the Response Evaluation Criteria in Solid Tumors (RECIST). Immunogenicity was assessed. The dHER2 immunotherapeutic was well tolerated: grade 1/2 adverse events (AEs) were most common. No cardiac events were observed and one patient experienced an asymptomatic decrease of left ventricular ejection fraction below the normal range (47 %). Both humoral and cellular immunogenicity to the dHER2 antigen was observed. No patient discontinued the immunizations because of AEs but 35/40 withdrew prematurely, 34 because of disease progression (24/34 before or at the tumor assessment after dose 6). One patient achieved a complete response lasting 11 months and one patient had a partial response lasting 3.5 months. Ten patients experienced stable disease ≥26 weeks with 4/10 still in stable disease at the last tumor assessment after 47 weeks. Immunization of MBC patients with the dHER2 immunotherapeutic was associated with minimal toxicity and no cardiac events. Clinical activity was observed with two objective responses and prolonged stable disease for 10/40 patients.
Safety of adjuvant trastuzumab for HER-2-overexpressing elderly breast cancer patients: a multicenter cohort study. [2015]For targeting anti-HER-2, trastuzumab-incorporated chemotherapy is the standard for HER-2-overexpressing breast cancer in adjuvant settings. But there are few data on trastuzumab in elderly patients. We evaluated the incidence of adverse events among an elderly population of trastuzumab-treated HER-2-positive breast cancer patients in adjuvant settings.
Phase 1 clinical trial of HER2-specific immunotherapy with concomitant HER2 kinase inhibition [corrected]. [2023]Patients with HER2-overexpressing metastatic breast cancer, despite initially benefiting from the monoclonal antibody trastuzumab and the EGFR/HER2 tyrosine kinase inhibitor lapatinib, will eventually have progressive disease. HER2-based vaccines induce polyclonal antibody responses against HER2 that demonstrate enhanced anti-tumor activity when combined with lapatinib in murine models. We wished to test the clinical safety, immunogenicity, and activity of a HER2-based cancer vaccine, when combined with lapatinib.
AE37: a novel T-cell-eliciting vaccine for breast cancer. [2014]Immunotherapy, including vaccines targeting the human EGFR2 (HER-2/neu) protein, is an active area of investigation in combatting breast cancer. Several vaccines are currently undergoing clinical trials, most of which are CD8(+) T-cell-eliciting vaccines. AE37 is a promising primarily CD4(+) T-cell-eliciting HER-2/neu breast cancer vaccine currently in clinical trials.
Clinical Development of the E75 Vaccine in Breast Cancer. [2020]E75 is an immunogenic peptide derived from the human epidermal growth factor receptor 2 (HER2) protein. A large amount of preclinical work evaluated the immunogenicity of E75, after which phase I trials investigated using E75 mixed with an immunoadjuvant as a vaccine. Those studies showed the vaccine to be safe and capable of stimulating an antigen-specific immune response. Subsequent to that, our group conducted trials evaluating E75 + granulocyte macrophage colony-stimulating factor (GM-CSF) in the adjuvant setting. The studies enrolled node-positive and high-risk node-negative breast cancer patients, with the goal being to determine if vaccination could decrease the recurrence risk. The studies included 187 evaluable patients: 108 vaccinated ones and 79 controls. The 5-year disease-free survival for the vaccinated patients was 89.7% compared to 80.2% for the control patients, a 48% reduction in relative risk of recurrence. Based on these data, E75 + GM-CSF, now known as NeuVax™, is being evaluated in a phase III trial. In this article, we review preclinical data and results of the early-phase trials and provide an update on the ongoing phase III study. We also present additional strategies for employing the vaccine to be included as a component of combination immunotherapy as well as in the setting of ductal carcinoma in situ as an initial step towards primary prevention.
A chimeric multi-human epidermal growth factor receptor-2 B cell epitope peptide vaccine mediates superior antitumor responses. [2020]Immunotherapeutic approaches to cancer should focus on novel undertakings that modulate immune responses by synergistic enhancement of antitumor immunological parameters. Cancer vaccines should preferably be composed of multiple defined tumor Ag-specific B and T cell epitopes. To develop a multiepitope vaccine, 12 high ranking B cell epitopes were identified from the extracellular domain of the human epidermal growth factor receptor-2 (HER-2) oncoprotein by computer-aided analysis. Four novel HER-2 B cell epitopes were synthesized as chimeras with a promiscuous T cell epitope (aa 288-302) from the measles virus fusion protein (MVF). Two chimeric peptide vaccines, MVF HER-2(316-339) and MVF HER-2(485-503) induced high levels of Abs in outbred rabbits, which inhibited tumor cell growth. In addition, Abs induced by a combination of two vaccines, MVF HER-2(316-339) and MVF HER-2(628-647) down-modulated receptor expression and activated IFN-gamma release better than the individual vaccines. Furthermore, this multiepitope vaccine in combination with IL-12 caused a significant reduction (p = 0.004) in the number of pulmonary metastases induced by challenge with syngeneic tumor cells overexpressing HER-2. Peptide Abs targeting specific sites in the extracellular domain may be used for exploring the oncoprotein's functions. The multiepitope vaccine may have potential application in the treatment of HER-2-associated cancers.
Primary analysis of a prospective, randomized, single-blinded phase II trial evaluating the HER2 peptide GP2 vaccine in breast cancer patients to prevent recurrence. [2022]GP2 is a HER2-derived, HLA-A2+ restricted peptide. Phase I studies showed GP2 administered with GM-CSF to be safe and immunogenic. Here we report the primary analysis of a prospective, randomized, multicenter phase II adjuvant trial conducted to determine the vaccine's efficacy. The trial enrolled HLA-A2+, clinically disease-free, node-positive and high-risk node-negative breast cancer patients with tumors expressing HER2 (immunohistochemistry[IHC] 1+-3+). Patients were randomized to GP2+GM-CSF versus GM-CSF alone. Disease-free survival (DFS) was analyzed in intention-to-treat (ITT) and per-treatment cohorts; pre-specified subgroup analyses were performed for patients with IHC 3+ or FISH+ disease. The trial enrolled 180 patients; 89 received GP2+GM-CSF and 91 received GM-CSF alone. The groups were well-matched for clinicopathologic characteristics. Toxicities have been minimal. The Kaplan-Meier estimated 5-year DFS rate in the ITT analyses was 88% (95% CI:78-94%) in vaccinated vs. 81% (95% CI:69-89%) (P = 0.43) in control patients after a 34 month median follow-up. In the per-treatment analysis, the estimated 5-year DFS rates were 94% (95% CI:83-98%) and 85% (73-92%) (P = 0.17). In IHC 3+/FISH+ patients, the estimated 5-year DFS rate was 94% (82-98%) in vaccinated patients (n = 51) vs. 89% (71-96%) in control patients (n = 50), (P = 0.86) in the ITT analyses and 100% vs. 89% (71-96%) in vaccinated vs. control patients in the per-treatment analyses (P = 0.08). While the overall ITT analysis did not demonstrate benefit to vaccination, this trial confirmed that the GP2 vaccine is safe and suggests that vaccination may have clinical activity, particularly in patients with HER2 overexpression who received the full vaccine series (ie per-treatment group).