Personalized Vaccine for TNBC Immunotherapy (TEBICA003 TNBC)

ESTUDIO CLÍNICO FASE I DE INMUNOTERAPIA CON VACUNAS SINTÉTICAS PERSONALIZADAS EN PACIENTES CON CÁNCER DE MAMA TRIPLE NEGATIVO

Due to their genetic instability, breast tumors that do not express receptors for Estrogens, Progestagens or amplify the Her2 / neu oncogene [called triple-negative breast cancer (TNBC)] and other tumors such as melanoma, non-small cell lung cancer, accumulate numerous mutations that make them highly resistant to different regimens of chemo- or radiotherapy, thereby generating high morbidity and mortality. However, immunology can turn the genetic instability of tumors into the Achilles' tendon. Evidence of this has been revealed in Phase I clinical studies in patients with melanoma and lung cancer in an advanced stage of metastasis treated with Ipilimumab (anti-CTLA4) to decrease immunosuppression, in whom peptides containing mutations presented in Major Complex molecules Histocompatibility of Class I (MHC I) of the tumor itself results in their recognition as "foreign" neo-antigens leading to the efficient destruction of the tumor by anti-tumor CD8 + T lymphocytes that are amplified when they are vaccinated with these peptides.

For this reason, the identification of non-synonymous mutations of single amino acid and vaccination with 25 amino acid peptides that incorporate these mutations (synthetic vaccines) is emerging today as an alternative for immunotherapy of cancers responsible for high mortality in humans. In an approach that takes 16 weeks, today, it is possible to go from the analysis of the tumor's transcriptome (which allows identifying the universe of tumor mutations) to the patient's vaccination with a personalized vaccine that contains neo-antigens of his tumor.

TNBC is the most aggressive breast tumor, representing around 15% of breast cancers in our environment. While generally, at least 30% of women with other types of metastatic breast cancer survive 5 years after diagnosis, most patients diagnosed with metastatic TNBC die within this time. The lack of selective therapies and the poor prognosis of patients with TNBC make their therapeutic management difficult, so the implementation of new therapies for this type of tumor is the main focus of researchers who seek more effective and selective treatments to improve the life expectancy of patients without compromising their quality of life. The genetic instability and high rate of mutations of the TNBC most likely favor the generation of neo-epitopes. Still, due to the immunosuppressive environment of the tumor, it escapes the immunosurveillance of the immune system. Despite the high mortality induced by this tumor, a percentage of patients treated with neoadjuvant chemotherapy with agents such as Doxorubicin and Cyclophosphamide (AC) + Taxanes respond to this chemotherapy regimen. In particular, the anti-tumor effect of AC is attributed to two things: (i) the direct cytotoxic effect on the tumor cell, (ii) the immunostimulation of T lymphocytes promoted by Immunogenic Cell Death (ICD) selectively induced by these drugs. Therefore, in this project, we propose to carry out the first clinical study in Colombia of vaccination of patients with TNBC with synthetic peptides that contain mutations of their own tumor to evaluate the immunogenicity and safety of this type of personalized vaccine as a therapeutic alternative for this tumor. Achieving the specific objectives set out in this project would mean that we have been validated in Colombia the experimental design necessary to identify unique epitopes in tumors and demonstrate the safety and immunogenicity of these vaccines. We consider that having achieved the above; we will have taken an important step towards the implementation in our country of the use of this type of vaccine for immunotherapy not only of TNBC but of other tumors such as glioblastoma, gastric, esophagus, and pancreas, highly fatal due to its high mutation rate.

Study Overview

• Status: Not yet recruiting
• Conditions: Breast Cancer Female
• Intervention / Treatment: Biological: Peptide pulsed autologous Dendritic cell

• Study Type: Interventional
• Enrollment (Estimated): 8
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Carlos A Parra-Lopez, MD PhD; Phone Number: 601-316-5000; Email: caparral@unal.edu.co
• Study Contact Backup: Name: David A Bernal-Estevez, MD PhD; Phone Number: 601-316-5000; Email: dbernal.investigacion@saluddelosandes.com

Study Locations

• Colombia
  • Bogota, Colombia, 111321
    • Facultad de Medicina - Universidad Nacional de Colombia
    • Contact: Carlos A Parra-Lopez, MD PhD; Phone Number: 15039 800-555-5555; Email: caparral@unal.edu.co
    • Contact: David A Bernal-Estévez, MD PhD; Phone Number: +57 310 5638254; Email: dbernal.investigacion@saluddelosandes.com
    • Principal Investigator: Carlos A Parra-Lopez, MD PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Be between 18 and 75 years of age.
2. Histologically confirmed diagnosis of primary triple negative breast carcinoma (TNBC).
3. Patients who have already been treated, either with chemo/radiotherapy and/or surgery regimens, and in whom, according to previous preclinical studies, it was possible to clearly identify tumor NEOANTIGENS expressed by their tumor.
4. Have frank venous access.
5. Have a functional status (Karnofsky Scale) greater than 70%.
6. Weight equal to or greater than 50 kilograms.
7. The chemical synthesis of at least one tumor NEOANTIGEN expressed exclusively by your tumor was successful.
8. The apheresis procedure successfully allowed the obtaining of sufficient white blood cells to obtain leukocytes necessary for functional tests and for the derivation of dendritic cells.

Exclusion Criteria:

1. Active and/or uncontrolled cardiovascular disease.
2. You are pregnant or breastfeeding.
3. Has associated medical comorbidities such as diabetes or kidney failure, or coagulation disorders.
4. You have been hospitalized in the last month.
5. Has another active primary tumor except for skin tumors.
6. Patients who are linked to another clinical study.
7. Patients with a history of infectious diseases such as HIV, Hepatitis, tuberculosis.
8. Consumption of immunosuppressive medications such as corticosteroids (except topical).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vaccine; Triple-negative breast cancer patients with specific tumor mutation, with six doses of peptide-pulsed autologous dendritic cells after surgery	Biological: Peptide pulsed autologous Dendritic cell; Intradermal vaccination with peptide-pulsed autologous dendritic cells in 200 µL of patient's serum in six doses weekly after surgery.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of adverse effects	Evaluation of number and severity of the adverse effects in the vaccinated patients	From day 0 (vaccination 1) until 3 month after last vaccination

Collaborators and Investigators

• Sponsor: Universidad Nacional de Colombia
• Collaborators: Fundación Salud de los Andes

Publications and helpful links

General Publications

• Bernal-Estevez DA, Ortiz Barbosa MA, Ortiz-Montero P, Cifuentes C, Sanchez R, Parra-Lopez CA. Autologous Dendritic Cells in Combination With Chemotherapy Restore Responsiveness of T Cells in Breast Cancer Patients: A Single-Arm Phase I/II Trial. Front Immunol. 2021 Aug 20;12:669965. doi: 10.3389/fimmu.2021.669965. eCollection 2021.

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2024
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: December 22, 2023
• First Submitted That Met QC Criteria: December 22, 2023
• First Posted (Estimated): January 8, 2024

Study Record Updates

• Last Update Posted (Estimated): January 8, 2024
• Last Update Submitted That Met QC Criteria: December 22, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Immunotherapy; Peptide; Dendritic cells; Triple negative breast cancer; Neo-adjuvant chemotherapy; Immune-monitoring; Personalized vaccines
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: TEBICA003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No