Phase 1/2 Trial to Evaluate the Safety and Efficacy of an Oral Personalized Vaccine in Patients with Locally Advanced Triple-Negative Breast Cancer

Breast cancer (mammary carcinoma) is one of the most common cancers among women. It is a malignant change in the breast tissue in which cells multiply uncontrollably. Treatment depends on the stage of the disease (stages 1–4) and the biological characteristics of the tumor cells. An important factor is whether the cancer cells express certain receptors on their surface, such as hormone receptors (estrogen, progesterone) or the growth factor receptor HER2 (HER2-positive). If all three of these target structures are absent, the cancer is referred to as triple-negative breast cancer. This is a particularly aggressive form, as it responds neither to anti-hormone therapies nor to HER2-targeted drugs. Therefore, treatment typically consists of intensive chemotherapy combined with modern immunotherapy—usually before surgery (neoadjuvant). Immunotherapy drugs help the immune system better recognize and fight cancer cells. The goal is to shrink the tumor and assess the treatment’s effectiveness even before surgery. After surgery, further chemotherapy or radiation therapy may follow, depending on the patient’s response to treatment and individual risk profile.

In this study, a new personalized vaccine called NECVAX-NEO1 is being tested in addition to the standard treatment. This vaccine is developed individually for each participating patient and contains selected “neoantigens”—small protein fragments found only in tumor cells. The vaccine is designed to specifically trigger an immune response against these tumor cells. It is administered in tablet form and is intended to help the immune system fight the cancer cells even more effectively.

The goal of this Phase-1/2 trial is to investigate the safety and efficacy of this personalized vaccine in combination with standard therapy (consisting of a PD-1 inhibitor as well as epirubicin/cyclophosphamide and Nab-paclitaxel chemotherapy) prior to surgery. All patients receive the same treatment (a single study arm) and are aware of it (open-label, unblinded design).

The study is divided into several phases: First, suitable neoantigens are selected for vaccine production, and treatment begins with the PD-1 inhibitor pembrolizumab and epirubicin/cyclophosphamide for up to 12 weeks. This is followed by a 12-week treatment phase with the vaccine and standard therapy (pembrolizumab and Nab-paclitaxel) leading up to surgery. In consultation with the study team, treatment with the vaccine in combination with pembrolizumab may be extended for an additional 24 weeks after surgery. This is followed by a follow-up period of up to two years to evaluate long-term safety and efficacy.

Eligible participants include women and men aged 18 and older with newly diagnosed stage 2 or 3 triple-negative breast cancer who are scheduled to receive neoadjuvant chemotherapy. Requirements include, among other things, adequate liver, kidney, and bone marrow function, as well as generally good health.