A clinical study with MK-2870 with and without Pembrolizumab compared to standard chemotherapy in participants with inoperable breast cancer.

Résumé de l'étude

The main objective of this study is to investigate the efficacy and safety of MK-2870 alone and in combination with Pembrolizumab compared to 4 standard chemotherapies. To this end, the safety and tolerability of MK-2870 will be evaluated by observing side effects occurring during the study. Additionally, it will be evaluated how long participants survive and how the quality of life of the participants changes. The participants in this study will be individuals with HR+/HER2- locally advanced or metastatic breast cancer that can no longer be surgically removed. At this stage, it may be that the cancer cannot be surgically removed, which is why chemotherapy is often the only treatment option. MK-2870 is an experimental drug composed of a monoclonal antibody in combination with a toxin (KL610023). Antibodies are proteins produced by the immune system that help the body fight foreign substances such as bacteria or viruses, but also tumors. Monoclonal antibodies bind to specific targets on cells. MK-2870 binds to a target on certain cancer cells known as trophoblast antigen 2 (TROP2). Through this binding, the toxin (KL610023) can damage these cancer cells. MK-2870 is not yet approved in Switzerland and is being tested in various studies for the treatment of diseases, including endometrial carcinoma (uterine cancer) and breast cancer. Pembrolizumab (MK-3475) is an antibody that can prevent the tumor from deceiving the immune system and thus enhance the body's natural fight against the tumor. In the study described here, approximately 1200 affected individuals are expected to participate worldwide. In Switzerland, about 15 affected individuals are expected to participate. The total duration of the study is approximately 9 years.

(BASEC)

Intervention étudiée

After a maximum 28-day pre-examination and clarification period, each participating individual will be randomly assigned to a treatment with only MK-2870, MK-2870 together with MK-3475, or a standard chemotherapy. The standard chemotherapy will be determined by the study physician before the random assignment of the group. The treatment duration is approximately 1 year. After treatment, the study participants will be observed regarding their health status.

After thorough information, precise eligibility assessment, and collection of medical history, the participant will be included in the study and randomly assigned in a ratio of 3:3:2 to one of the following groups:

Group 1: Participants receive only MK-2870

Group 2: Participants receive MK-2870 together with Pembrolizumab

Group 3: Participants receive a standard chemotherapy.

Pembrolizumab (MK-3475) and MK-2870 will be administered via a needle in the arm. This is referred to as intravenous (i.v.) infusion. MK-2870 will be administered every 2 weeks, Pembrolizumab every 6 weeks. Depending on the standard chemotherapy, this may also be administered intravenously or as a tablet. The administration cycle depends on the respective standard chemotherapy.

This study is a so-called "open-label" study. This means that both the participants and the study physician and the sponsor know which group they have been assigned to and thus also whether they are receiving only MK-2870, MK-2870 with Pembrolizumab, or chemotherapy.

As part of study visits, various measures and examinations may take place, such as electrocardiogram (ECG), echocardiogram (ECHO), blood and urine tests, tumor biopsy sampling, imaging examinations of the chest and abdomen (CT, MRI, PET or X-ray), assessment of general health status, and discussions with medical staff. The study team may also contact participants between visits and after the end of the study drug intake to inquire about their health status.

(BASEC)

Maladie en cours d'investigation

Breast cancer is the most commonly diagnosed malignant cancer in women and the leading cause of cancer-related deaths. Breast cancer can be divided into subcategories based on the presence of different receptors on cancer cells. With approximately 68% of all breast cancer cases, the HR+/HER2- (hormone receptor positive / epidermal growth factor receptor negative) type of breast cancer being studied in this study is the most common type. Individuals with this type of cancer have a good prognosis if breast cancer is detected at an early stage. Then, the likelihood of recurrence after treatment is low. However, if breast cancer is discovered only when there are already distant metastases, the 5-year survival probability is only 30%. Therefore, treatment of individuals with distant metastases aims to prolong life and maintain quality of life. The diagnosis of HR+/HER2- breast cancer is made based on various examinations, including a tissue biopsy. The assessment of the different receptors is crucial for the further treatment of breast cancer. Thus, HR+ (hormone receptor positive) means that breast cancer cells have proteins that bind to the hormones estrogen and progesterone, which can promote the growth of cancer cells. HER2- (human epidermal growth factor receptor 2 negative) means that the cancer cells do not produce high amounts of the HER2 protein. HR+/HER2- breast cancer is initially treated with medications that block or reduce the effect of estrogen on cancer cells. These medications can prolong the time until progression. However, over time, the cancer may continue to develop and become resistant, causing the therapy to lose its benefit. Individuals with resistant breast cancer are therefore treated further with chemotherapy. The benefit of chemotherapy is, however, uncertain and depends on other factors, such as the course of therapy or the time since the last treatment. For individuals with advanced HR+/HER2- breast cancer, for whom only chemotherapy is an option, further treatment approaches are relevant to achieve better results. This study is aimed at individuals with inoperable, locally advanced or metastatic HR+/HER2- breast cancer.

(BASEC)

Sponsor

MSD Merck Sharp & Dohme AG, Switzerland Merck Sharp & Dohme LLC, USA

(BASEC)

Nom du comité d'éthique approbateur (pour les études multicentriques, uniquement le comité principal)

Commission cantonale de Zurich

(BASEC)

Date d'approbation du comité d'éthique

07.05.2024

(BASEC)

Résultats de l'essai