A study comparing the new drug izalontamab brengitecan with standard chemotherapy as first-line treatment for advanced triple-negative or hormone receptor-low breast cancer (IZABRIGHT-Breast01)

Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer in which the tumor cells do not express hormone receptors (ER/PgR) and do not show excessive HER2 signaling. In ER-low, HER2-negative breast cancer, ER/PgR levels are only low (1–10%). As a result, standard hormone or HER2-targeted therapies are ineffective. First-line treatment consists of chemotherapies such as taxanes (paclitaxel/nab-paclitaxel), platinum plus gemcitabine, or capecitabine. For PD-L1-positive TNBC tumors, immunotherapy may also be used; however, this is not an option for the patient group in this study (e.g., PD-L1-negative, autoimmune disease, or relapse occurring too soon after anti-PD-(L)1 treatment). Iza-bren is a bispecific antibody-drug conjugate that simultaneously targets two specific receptors, EGFR and HER3, on tumor cells. This allows the active ingredient—a topoisomerase inhibitor—to be delivered specifically into the cancer cells to block their DNA repair and kill the cells.

The goal of this Phase 2/3 study is to determine whether the investigational drug izalontamab-brengitecan (shortened to “iza-bren”) is more effective and better tolerated than standard chemotherapy chosen by the treating physician. The study is a comparative, randomized, open-label trial involving 500 participants worldwide. There are three groups in total: Groups 1 and 2 will receive iza-bren, and a third control group will receive standard chemotherapy with paclitaxel, nab-paclitaxel, carboplatin + gemcitabine, or capecitabine. The primary endpoint is progression-free survival—that is, the time until disease progression as assessed by an independent, blinded central imaging review. The study will run for a period of up to approximately 57 months.

Eligible participants include women and men aged 18 and older with confirmed breast cancer at the locally advanced, recurrent, or metastatic stage who have not previously received systemic treatment for this incurable condition. The disease must be measurable on imaging. This includes, on the one hand, people with triple-negative breast cancer (TNBC) or people with ER-low, HER2-negative breast cancer, in whom ER and/or PgR are only weakly expressed (1–10%). If the disease has recurred after prior curative treatment, the recurrence must have occurred at least 6 months ago. For patients with TNBC, an additional requirement is that they are not eligible for first-line anti-PD-1/PD-L1 immunotherapy. For ER-low, HER2-negative breast cancer: Based on the physician’s assessment, endocrine (hormonal) treatments are not appropriate.