A Study of the New Drug Tersolisib in Combination with Anti-Hormonal Therapy and a CDK4/6 Inhibitor in Patients with Advanced Breast Cancer with a PIK3CA Mutation (PIKALO-2)

Breast cancer (mammary carcinoma) is a malignant disease of the breast gland tissue characterized by the uncontrolled proliferation of breast gland cells. Treatment depends on numerous factors, such as the stage of the disease, the presence of detectable hormone receptors on the surface of the cancer cells, and the presence of HER2 receptors. If the cancer cells have hormone receptors, their growth is often stimulated by hormones such as estrogen. Anti-hormone therapy can block these hormonal growth signals and thereby slow tumor growth. In addition, a CDK4/6 inhibitor is often administered, which can enhance the effect of anti-hormone therapy by inhibiting the division of cancer cells. In some patients with breast cancer, the cancer cells exhibit a so-called PIK3CA mutation. This is a genetic alteration that permanently activates a specific signaling pathway (the PI3K pathway) in the cancer cells, thereby promoting tumor growth. Tersolisib (also known as STX-478 or LY4064809) is a new oral medication in tablet form. It specifically targets cancer cells with a mutation in the PIK3CA gene. The goal is to inhibit the growth signals of the tumor cells while affecting normal cells as little as possible. The drug has not yet been approved for the treatment of this disease.

The goal of the Phase 3 study is to investigate whether the additional administration of tersolisib in combination with standard therapy can lead to tumor shrinkage (objective response rate, ORR) and delay disease progression (progression-free survival, PFS) in patients with advanced breast cancer. Standard therapy consists of anti-hormonal therapy with the additional administration of a CDK4/6 inhibitor, with the choice of specific medications left to the treating physicians. The study is divided into two parts. In Part 1, the appropriate dosage of tersolisib will be determined. In Part 2, patients will be randomly assigned to two groups: The treatment arm receives tersolisib in combination with a CDK4/6 inhibitor and anti-hormone therapy, while the control arm receives a placebo in combination with the same standard medications. Part 2 of the study is conducted as a double-blind trial, which means that neither the patients nor the study physicians know which group the patients have been assigned to. All medications are taken as tablets, with the exception of fulvestrant (hormone therapy), which is administered as an intramuscular injection.

Eligible participants include women and men aged 18 and older with hormone receptor-positive, HER2-negative, locally advanced, or metastatic breast cancer in whom a specific genetic alteration in the cancer cells (PIK3CA mutation) has been detected. For Part 1, patients who have already received up to two treatments for their advanced disease are eligible to participate. For Part 2, patients who have not yet received any treatment for their advanced disease are eligible. The study includes both patients whose tumors remain responsive to anti-hormone therapy and patients whose disease has progressed despite such treatment (treatment-refractory).