New Active Ingredient for Advanced Solid Tumors (AVZO-021)

Solid tumors are growths of tissue that can develop in various organs or body tissues. They can be benign or malignant. In cases of locally advanced or metastatic disease (Stage 4), a cure is usually no longer possible. In such cases, the goal of treatment is to control the progression of the disease for as long as possible.

Among other things, this study examines hormone receptor-positive, HER2 receptor-negative breast cancer as well as tumor types with cyclin E1 (CCNE1) alterations. In this type of breast cancer, the tumor cells are stimulated to grow by female hormones such as estrogen or progesterone. If no receptors are detectable on the breast cancer tumor cells, the cancer is referred to as triple-negative. This type of breast cancer is also included in the study.

In addition, the study focuses on so-called CCNE1-amplified cancers, such as epithelial ovarian carcinoma (EOC), primary peritoneal carcinoma (peritoneal cancer), and fallopian tube carcinoma. In this genetic alteration, certain genes that regulate cell growth are altered, which can accelerate tumor growth.

A group of proteins that regulate cell growth and cell division are the so-called cyclin-dependent kinases (CDKs). For certain types of breast cancer, blocking the CDK4 and CDK6 proteins is already part of standard treatment—for example, with drugs such as palbociclib. A related protein called CDK2 also plays an important role in the proliferation of cancer cells. Drugs that specifically inhibit CDK2 have not yet been approved, but are currently being investigated in clinical trials. In laboratory experiments and animal models, these compounds have already demonstrated a significant inhibitory effect on tumor growth—both on their own and in combination with CDK4/6 inhibitors. Therefore, research is currently underway to determine whether a targeted CDK2 inhibitor could also be effective in certain advanced cancers, particularly where CDK2 plays a central role in tumor growth (e.g., CCNE1-amplified tumor types) and other therapies are no longer sufficiently effective. For example, in hormone receptor-positive breast cancer, it is suspected that when resistance to CDK4/6 inhibitors develops, CDK2 inhibitors play a greater role in tumor growth. To date, CDK2 inhibitors have not yet been approved for treatment. The therapy is experimental.

The goal of this Phase 1/2 study is to test the new CDK2 inhibitor AVZO-021, both as a monotherapy and in combination with other medications, in various advanced solid tumor diseases. First, the maximum tolerated dose and the recommended dose will be determined (Phase 1), and the efficacy of the determined dose will be evaluated (Phase 2). To this end, patients will be divided into different groups based on tumor type and prior treatment. The treatment a patient receives—that is, whether AVZO-021 is administered alone (monotherapy) or in combination with other medications—depends on the specific type of cancer, the patient’s genetic profile, and previous treatments. This assignment is made by the study team based on established scientific criteria. The drugs that may be administered as part of combination therapy are already approved for the treatment of various types of cancer. AVZO-021 is typically taken once daily as a tablet in 28-day cycles. The maximum tolerated and recommended dose will be monitored in Phase 1 for up to 22 months. In Phase 2, efficacy will be evaluated over a period of up to 76 months. Since Phase 1 and Phase 2 sometimes involve different patient groups, there is no automatic transition from one phase to the next. If patients are eligible to participate in Phase 2, they are generally enrolled anew for that phase. The study is open-label, meaning that both the medical staff and the patient know which treatment is being administered.

Women and men aged 18 and older who have advanced or metastatic solid tumors and for whom previous standard treatments have no longer been sufficiently effective are eligible to participate in the study. Patients with hormone receptor-positive, HER2-negative breast cancer, CCNE1-amplified tumors (epithelial ovarian carcinoma, primary peritoneal carcinoma, fallopian tube carcinoma), as well as triple-negative breast cancer (TNBC) with a CCNE1 alteration. A wide variety of other solid tumors suspected of being CDK2-dependent may also be eligible to participate in this phase of the study under certain circumstances. Participation is generally possible if the disease is in a late line of therapy, i.e., after several prior treatments have already been administered. In Phase 2, only certain tumor types are further investigated, including hormone receptor-positive, HER2-negative breast cancer, triple-negative breast cancer, and CCNE1-amplified tumors (ovarian, uterine, or peritoneal cancer). As in Phase 1, participation is only possible if the disease is in a late line of treatment. In both phases, inclusion depends on various other factors.