Comparison of New Treatment Options for Advanced, Inoperable Breast Cancer

Breast cancer (mammary carcinoma) is a malignant disease of the breast gland tissue characterized by the uncontrolled proliferation of breast gland cells. In advanced stages, the tumor can spread to other organs (metastasize) or grow to the point where it can no longer be surgically removed. Treatment depends on various factors, including the patient’s overall health, tumor stage, and specific biological characteristics such as the growth rate (e.g., Ki-67 index), the presence of hormone receptors (estrogen/progesterone receptors), HER2 status, and genetic alterations such as PIK3CA mutations.

The goal of this Phase 1/2 study is to evaluate new treatment approaches for different groups of breast cancer patients. The Morpheus-panBC study is being conducted as a so-called umbrella study because it simultaneously investigates several different therapeutic approaches tailored to the individual needs and circumstances of the patients. This study design is particularly well-suited for complex diseases such as breast cancer. Under the “umbrella” of this single diagnosis, various subgroups are then formed. As part of the study, patients are randomly assigned to a treatment group based on their tumor’s biological characteristics. The study is open-label, meaning that both patients and the medical team know which drug is being administered. A complete list of all medications is provided at the end of the study description. Treatment is administered in cycles of 21 to 28 days and is continued as long as it is effective or well tolerated. The total duration of the study is scheduled to run through 2028.

Active recruitment (participation is possible) is currently underway in two study arms. The first involves patients who have the following biological tumor characteristics: hormone receptor-positive, HER2-negative, and who have a PIK3CA mutation (Cohort 3). Here, combinations of the targeted PI3K inhibitor inavolisib with modern hormone therapies and CDK4/6 inhibitors are being used. Among other combinations being tested are: inavolisib with abemaciclib and fulvestrant; inavolisib combined with ribociclib and fulvestrant; inavolisib combined with ribociclib and letrozole; and inavolisib combined with abemaciclib and letrozole. The goal of these combinations is to control tumor growth through targeted inhibition of hormonal and intracellular growth pathways.

Two treatment arms are also being continued for patients with HER2-positive or HER2-low (low expression) breast cancer and a PIK3CA mutation, in whom the disease has progressed despite standard therapy (Cohort 4). Both arms rely on a combination of inavolisib with trastuzumab deruxtecan, a modern antibody-drug conjugate that specifically targets HER2-expressing tumor cells.

Recruitment has already been completed for two groups: for patients with triple-negative (hormone receptor-negative and HER2-negative), PD-L1-positive breast cancer who have not previously received systemic therapy for their metastatic disease (Cohort 1) and for patients with triple-negative breast cancer whose disease has progressed after initial chemotherapy and who have not yet received immunotherapy (Cohort 2).

Patients who are at least 18 years old, in good general health (ECOG 0 or 1), and have inoperable, advanced, or metastatic breast cancer are eligible to participate in the study. Women must avoid becoming pregnant and use contraception. Exclusion criteria for study participation include, among others, prior immunotherapy, active autoimmune diseases, untreated brain metastases, severe infections, or a history of other cancers.