Study of the new active ingredient GVV858, either alone or in combination with anti-hormone therapy, in advanced breast cancer and other advanced solid tumors

Breast cancer (mammary carcinoma) is a malignant disease of the breast tissue in which cells multiply uncontrollably. Treatment depends, among other factors, on the stage of the disease and the biological characteristics of the tumor. In the early stages of the disease, the goal is usually to surgically remove the tumor. For advanced hormone receptor-positive breast cancer, anti-hormone therapy (e.g., fulvestrant or letrozole) may be used, which is intended to inhibit the effects of sex hormones and thereby slow cancer growth. Anti-hormone therapy can be combined with a CDK4/6 inhibitor. CDK4/6 inhibitors block the two proteins CDK4 and CDK6, which drive the cell cycle, so that cancer cells divide more slowly or stop dividing altogether. In advanced stages, prostate cancer can spread to other parts of the body and form secondary tumors (metastases) there. Since the male sex hormone testosterone can promote the growth of prostate cancer cells, testosterone levels are significantly reduced as part of anti-hormone therapy. If the disease continues to progress despite persistently low testosterone levels, it is referred to as castration-resistant prostate cancer. In various advanced solid tumors, certain genetic changes can also occur in the cancer cells. These include what is known as CCNE1 amplification, in which there are too many copies of the CCNE1 gene. This gene is involved in regulating cell division, so an increased number of gene copies can promote the growth and proliferation of cancer cells. GVV858 is a new drug for the treatment of advanced cancers that is being studied in humans for the first time in this trial.

The goal of the study is to investigate the safety and tolerability of the new drug GVV858, both as a monotherapy and in combination with anti-hormone therapy (fulvestrant or letrozole), and to determine the appropriate dose range for further studies. In the Phase 1 portion, patients will receive GVV858 alone or, in the case of breast cancer, in combination with fulvestrant or letrozole, with the dosage being increased gradually. In the subsequent Phase 2 part, GVV858 will be studied in combination with fulvestrant at two different dosages for breast cancer. For this purpose, patients will be randomly assigned to two treatment groups. The study is open-label, which means that both the patients and the study physicians know which treatment is being administered.

Patients aged 18 and older with advanced hormone receptor-positive, HER2-negative breast cancer that has progressed while on anti-hormone therapy with a CDK4/6 inhibitor, another advanced or metastatic solid tumor with CCNE1 amplification, or metastatic castration-resistant prostate cancer are eligible to participate in this study.