A Vaccine (STEMVAC) for Improving Survival in Patients With Triple-Negative Breast Cancer and Moderate or Extensive Residual Cancer Burden

Официальное название

A Multiantigen Vaccine (STEMVAC) for Adjuvant Treatment of Patients With Moderate or Extensive Residual Triple-Negative Breast Cancer

Обзор

This phase II trial evaluates whether a multi-antigen vaccine called STEMVAC improves disease-free survival after surgery in patients with triple-negative breast cancer (TNBC) and moderate or extensive residual cancer burden. TNBC has an aggressive clinical course and poorer disease-free survival compared to other subtypes. While patients who have no remaining tumor in the breast or lymph nodes after surgery have excellent long-term outcomes, patients with moderate or extensive residual cancer burden remain at high risk for early disease return and poorer prognosis. STEMVAC is designed to target proteins that tumor cells use when they become more aggressive and start to spread, and it is believed to work by boosting the immune system to recognize and destroy the invader tumor cells that are causing the disease. Giving STEMVAC after surgery may improve disease-free survival rates in TNBC patients with moderate or extensive residual cancer burden.

Подробное описание

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients receive CD105/Yb-1/SOX2/CDH3/MDM2-polyepitope plasmid deoxyribonucleic acid (DNA) vaccine (STEMVAC) with recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) intradermally (ID) every 3 weeks for 3 doses. Patients then receive booster vaccines ID 9 weeks after vaccine 3 and 18 weeks after booster 1. Patients also undergo collection of blood samples throughout the trial.

ARM B: Patients receive GM-CSF ID every 3 weeks for 3 doses. Patients then receive booster vaccines ID 9 weeks after vaccine 3 and 18 weeks after booster 1. Patients also undergo collection of blood samples throughout the trial.

After completion of study treatment, patients are followed up at 3 weeks after their last vaccination and then every 6 months for 3 years.

Вмешательства

• Биопрепарат CD105/Yb-1/SOX2/CDH3/MDM2-polyepitope Plasmid DNA Vaccine
  Given ID
• Препарат Recombinant Granulocyte-Macrophage Colony-Stimulating Factor
  Given ID
• Процедура Biospecimen Collection
  Undergo collection of blood samples

Первичные конечные точки

• Invasive breast cancer free survival (IBCFS) [Срок оценки: Time from randomization to local or distant recurrence or death, assessed up to 3 years]
• Dynamics and characteristics of circulating tumor deoxyribonucleic acid (ctDNA) [Срок оценки: Up to 3 weeks after last vaccination]

Вторичные конечные точки (3)

• Incidence of adverse events [Срок оценки: Up to 3 weeks after last vaccination]
• Immune response [Срок оценки: Up to 3 weeks after last vaccination]
• Expression of epithelial to mesenchymal transformation (EMT)-associated genes [Срок оценки: Archival tissue is collected after enrollment, within 30 days of baseline visit]

Критерии участия

Критерии включения

• At least 18 years of age
• Eastern Cooperative Oncology Group (ECOG) performance status score of ≤ 2
• Triple-negative breast cancer as determined by the treating oncologist
• Completed standard of care neoadjuvant chemotherapy in the opinion of their treating oncologist
• Patients whose tumors progress on neoadjuvant therapy may be enrolled
• No clinical evidence of local or distant recurrence
• Plan to receive standard of care adjuvant directed therapy
• Completed standard of care locoregional treatment, including definitive breast and lymph node surgery followed by standard radiation therapy, if recommended
• Residual cancer burden (RCB) index 2 or 3 as calculated per routine anatomic pathology clinical standards
• Absolute neutrophil count (ANC) ≥ 800/μL (within 30 days of first study vaccine administration)
• Hemoglobin (Hgb) ≥ 8 g/dL (within 30 days of first study vaccine administration)
• Platelets ≥ 75,000/ μL (within 30 days of first study vaccine administration)
• Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN), except patients with Gilbert's syndrome, in whom total bilirubin must be < 3.0 mg/dL (within 30 days of first study vaccine administration)
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 1.5 x institutional ULN (within 30 days of first study vaccine administration)
• Creatinine ≤ 1.5 x ULN mg/dL or creatinine clearance > 60 mL/min (within 30 days of first study vaccine administration)
• At least 28 days post systemic steroids prior to enrollment, unless used as part of prophylaxis to prevent intravenous (IV) contrast reactions.

• Topical, ocular, intra-articular, intranasal, inhalational corticosteroids (with minimal systemic absorption) are allowed
• Must have recovered from major infections and/or surgical procedures; and in the opinion of the investigator, not have any significant active concurrent medical illnesses or condition precluding protocol treatment
• Patients of child-bearing potential must agree to use dual methods of contraception and have a negative urine pregnancy test at screening, and male patients must use an effective barrier method of contraception if sexually active with a person of child-bearing potential. Acceptable methods of contraception are abstinence, condoms with contraceptive foam, oral, implantable or injectable contraceptives, contraceptive patch, intrauterine device, diaphragm with spermicidal gel, or a sexual partner who is surgically sterilized or post-menopausal

Критерии исключения

• Toxicities related to prior exposure to immune checkpoint inhibitors for which immune checkpoint inhibitors cannot be safely continued as determined by study investigator
• Germline BRCA1 or BRCA2 mutations with adjuvant olaparib planned within the study period

• NOTE: If olaparib is not planned, then these patients are eligible
• Any known cardiac conditions:

• Symptomatic restrictive cardiomyopathy
• Dilated cardiomyopathy
• Unstable angina within 4 months prior to enrollment
• New York Heart Association functional class III-IV heart failure on active treatment
• Symptomatic pericardial effusion
• Autoimmune disease requiring active systemic treatment
• Known hypersensitivity reaction to the GM-CSF adjuvant; any known contra-indication to GM-CSF
• Pregnant or breast feeding
• Known history of human immunodeficiency virus (HIV) infection, hepatitis B (e.g., hepatitis B virus surface antigen \[HBsAg\] reactive), or hepatitis C (e.g., hepatitis C virus \[HCV\] ribonucleic acid \[RNA\] is detected)
• Major surgery within the 4 weeks prior to initiation of first study vaccine
• Enrollment in any other clinical protocol or investigational trial that involves concurrent administration of experimental therapy and/or therapeutic devices, or investigational drug. Patients who completed prior clinical trials (such as neoadjuvant treatment, surgery or radiation trials) and are on long term follow up are permitted

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• Fred Hutch/University of Washington Cancer Consortium — Seattle

Идентификаторы

NCT: NCT07721259 · RG1126489 · NCI-2026-04722

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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