Treatment of Advanced Breast Cancer with the Antibody-Drug Conjugate Disitamab Vedotin in Patients with Different HER2 Expressions

Breast cancer (mammary carcinoma) develops as a result of uncontrolled cell growth in the breast tissue. The tumor cells can exhibit various surface characteristics that are crucial for selecting a treatment. One of these characteristics is the HER2 receptor, which can be present on cancer cells in varying amounts: highly overexpressed (HER2-positive), present in lower amounts (HER2-low), or present in very low amounts (HER2-ultra-low). HER2 stimulates increased growth of cancer cells, which is why it serves as a target for targeted therapies. In advanced or metastatic stages, a cure is generally no longer possible, so the goal of treatment is to control the progression of the disease for as long as possible and to maintain quality of life. Disitamab vedotin is an antibody-drug conjugate consisting of an antibody directed against HER2 and a cytotoxic agent (MMAE) linked to it. The antibody specifically recognizes the HER2 receptor on the surface of cancer cells, binds to it, and is taken up into the tumor cell along with the cytotoxic agent. Once inside, the cytotoxic agent is released, inhibits cell division, and triggers cell death. The drug is administered as an intravenous infusion every two weeks.

The goal of this Phase 1b/2 study is to investigate the safety and efficacy of the antibody-drug conjugate disitamab vedotin based on the expression level of the HER2 receptor. There are three cohorts, which differ based on the HER2 and hormone receptor status of the tumors; in all cohorts, disitamab vedotin is administered as a single therapy (monotherapy) every two weeks via intravenous infusion. The study is open-label, meaning that both the patients and the study physicians know which treatment is being administered. Treatment will continue until the disease progresses or the patient can no longer tolerate it. After treatment is completed, follow-up appointments are scheduled every six weeks. Thereafter, follow-up appointments take place every twelve weeks via telephone. The main objective (primary endpoint) of the study is the response to therapy over a period of up to two years.

Women and men aged 18 and older with locally advanced or metastatic (spread to other parts of the body) breast cancer who have already received prior treatment are eligible to participate in this study. The HER2 receptor status and hormone receptor status must be known. Cohort 1 includes patients with HER2-positive breast cancer, Cohort 2 includes patients with hormone receptor-positive and HER2-low breast cancer, and Cohort 3 includes patients with hormone receptor-positive and HER2-ultra-low or hormone receptor-negative and HER2-low breast cancer.